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megalomania
April 6th, 2005, 11:49 PM
I find it curious that in the paper Mr Samosa provided, http://www.geocities.com/hammsterr/NovDAGVGP.doc that the review of the book "Handbook of Chemical and Biological Warfare Agents" is no longer at amazon.com. I went there a few days ago to see about buying the book (screw that is too expensive) because EVERY copy in the network of libraries is either restricted or checked out for the next several months. I would like to know what kind of person can check out a book for months at a time :(

Anyway, I looked over the reviews to see if there was anything else, and imagine my suprise to see nothing for December 14, 2003. In fact there is nothing from Anatoly Kuntsevich. It looks like Amazon has censored the review. I see they have a complaint system in place to rat on undesirable articles. Perhaps the review hit a little too close to home for some government stooge to tolerate.

simply RED
April 7th, 2005, 06:28 AM
The process using tris and POCl3 or P2O5 is very interesting as
theory suggests - cyclic product will be formed with high yield.
(theory of antiperiplanar groups, quantum calculations, thermodinamics - delta

G less than zero , general organic reactions theory ( metaphase formation )


Solvent maybe ether (or THF) + H3PO4. In proportions to produce homogenous mix.

simply RED
April 7th, 2005, 06:28 AM
The process using tris and POCl3 or P2O5 is very interesting as
theory suggests - cyclic product will be formed with high yield.
(theory of antiperiplanar groups, quantum calculations, thermodinamics - delta

G less than zero , general organic reactions theory ( metaphase formation )


Solvent maybe ether (or THF) + H3PO4. In proportions to produce homogenous mix.

simply RED
April 7th, 2005, 06:28 AM
The process using tris and POCl3 or P2O5 is very interesting as
theory suggests - cyclic product will be formed with high yield.
(theory of antiperiplanar groups, quantum calculations, thermodinamics - delta

G less than zero , general organic reactions theory ( metaphase formation )


Solvent maybe ether (or THF) + H3PO4. In proportions to produce homogenous mix.

MrSamosa
April 10th, 2005, 08:42 PM
Curse censorship, but thank God for Google caches and cheap websites who copy reviews from Amazon.com :) . Fear not Mega, all is not lost. But it is being lost faster than I thought... I used to find copies of that review all over Google, but the numbers are dwindling. So for safe-keeping, I'll put the original reviews right here in this thread; as you will see, most of my editing was for the sake of clarity--fixing grammar, rewording sentences, adding pictures.

Novichok(s), dusty agents and GV/GP agents, December 14, 2003
Reviewer: Anatoly Kuntsevich from Moscow, Russia
Although this book is missing the chemistry of the Novichok class of nerve agents it summarizes the physico-chemical data of the known CWAs. Most of the data are taken from the older Field Manual FM 3-9 (1990). The expert may find that some of the data are only estimated, but not indicated as such. Only the details of GV-4 alias EA-5414 (CAS RN 158847-17-7) and GP/GV alias EA-5365 (CAS RN 141102-74-1) are new revelations to the public.

The Novichok class of chemical warfare agents belongs to those organophosporus compounds containing also a dihaloformaldoxime group: -O-N=C(X)Y group (X,Y = Cl, F, Br or even stable pseudohalogens such as C#N). Two examples of Novichok compounds are
a) Smiles: P(F)(=O)(O\N=C(/Cl)F)OCCCl with CAS RN 26102-97-6 and
b) Smiles: F/C(Cl)=N\OP(=O)(OCC)N(C)CCCl with CAS RN 26102-99-8
as published in Kruglyak, Yu. L.; Malekin, S. I.; Leibovskaya, G. A.; Khromova, Z. I.; Sretenskaya, I. I.; Martynov, I. V.: Reaction of alpha-chloronitrosoalkanes with phospholanes and iminophosphites, Khim. Primen. Fosfororg. Soedin., Tr. Konf., 4th (1972), Meeting Date: 1969, p. 307-312. Editor: Grechkin, N. P. Publisher: Nauka, Moscow, USSR. In fact the group of Novichok CWAs is quite large and it would be difficult to protect soldiers and civil personnel, when many different chemicals belonging this class of CWA could be used in chemical warfare with rogue nations or terrorists.

Several Russian chemists as P.P. Kirpichev, R.K. Bal'chenko, I.V. Martynov, Yu.A. Kruglyak, S.I. Malekin, and N.F. Privezentseva from the Moscow institutes GosNIIOKhT and INEOS developed
the principle of these extremely toxic OP haloformaldoximes already during the mid 60's. Rapid progress toward supertoxic variants was seen in the early 70's and the synthesis details were indeed published mainly in the Journal of General Chemistry (Zhurnal Obshchei Khimii), although absolutely no toxicity data of the Novichoks were revealed. All activities were covered as research for pesticides at that time. All publication activities of these authors ceased at the end of 1972.

Michael Crichton alias John Lange published in 1972 the thriller "Binary" which alarmed Russian politicians and military personnel to act quickly on the looming threat of US binary chemical weapons. In 1973 the further activities in the USSR under the new Foliant program were disguised again as a pesticide research program but kept secret until 1986 when some of the researches could publish more details about chemical and biological effects of phosphorylated oximes (e.g. Raevskii, 0. A.; Chapysheva, N. V.; Ivanov, A. N.; Sokolov, V. B.; Martynov, I. V., Effect of alkyl substituents in phosphorylated oximes, Zhurnal Obshchei Khimii (1987), 57(12), 2720-2723 and Raevskii, O. A.; Grigor'ev, V. Yu.; Solov'ev, V. P.; Ivanov, A. N.; Sokolov, V. B.; Martynov, I. V., Electron-donor functions of ethyl methylchloroformimino methylphosphonate, Zhurnal Obshchei Khimii (1987), 57(9), 2073-8)). It became clear that Novichoks do resist strongly poisoned Acetylcholinesterase/Butyrylcholinesterase reactivation by other common oximes (e.g. 2-PAM/EA-2170, TMB-4/EA-1814) as used so far by the American military forces. The final details to US authorities were given by Vil S. Mirzayanov alias Kenneth (Ken) Alibek who was responsible to detect any Novichok traces in the environment of the GosNIIOKhT branch no. 4 (CWA plant for Novichok) at Vol'sk-17 by gas chromatography. He, as an long standing expert in gas chromatography having the details of what he had to look for in the analyses defected to the US in 1992.

Since the beginning of the 90's US chemical demilitarization programs in the former GUS also included joint research on Novichoks. Now in order to develop effective detectors, detoxifiers, reactivators and bioscavengers (including BuChE). All such programs were named under activities versus "Fourth Generation Agents" (FGA) or "Non-Traditional Agents" (NTA). It seems each year is now coming up with a new disguising term in order not to use "Novichok" in public US documents. "Dusty agents" are also not covered in Ellison's handbook but should be seen in conjunction with the Novichok developments during the 70's and 80's. The Russian researchers V.A. Pasechnik, O.I. Stuzhuk, and Ye.A. Gayev contributed to this development. O.I. Stuzhuk proposed special minerals and diatoms for being contaminated with CWAs, whereas Ye. A. Gayev developed the physical CWA spraying/aerosol system and V.A. Pasechnik contributed to the development and application of "dusty agents" containing biological weapons.


More details would be fine, November 16, 2003
Reviewer: Anatoly Kuntsevich (Moscow, Russia) - See all my reviews
Although this book does not reveal the precise chemical formulas for the Novichok class of nerve agents it introduces into the hidden world of russian chem-bio weapon designers. The intelligence still fears to make public that Novichoks belong to organophosporus compounds containing the double halogenated oxime like -O-N=C(F)Cl group and that beside P.P.Kirpichev also I.V.Martnov and Yu.A.Kruglak from GosNIOKhT developed the principle of these extremely toxic OP oximes during the mid 60's already (and published also) which resist reactivation by other oximes. These chemicals an be made by heating only of substituted 1,3,2-dioxaphospholanes indicated slighly in this book. Hopefully int'l organizations will make public more details for the protection of other citizens than just army soldiers soon. (Review for Cassidy's Run: The Secret Spy War over Nerve Gas (Thorndike Press Large Print Core Series) [LARGE PRINT] )

MrSamosa
April 10th, 2005, 08:42 PM
Curse censorship, but thank God for Google caches and cheap websites who copy reviews from Amazon.com :) . Fear not Mega, all is not lost. But it is being lost faster than I thought... I used to find copies of that review all over Google, but the numbers are dwindling. So for safe-keeping, I'll put the original reviews right here in this thread; as you will see, most of my editing was for the sake of clarity--fixing grammar, rewording sentences, adding pictures.

Novichok(s), dusty agents and GV/GP agents, December 14, 2003
Reviewer: Anatoly Kuntsevich from Moscow, Russia
Although this book is missing the chemistry of the Novichok class of nerve agents it summarizes the physico-chemical data of the known CWAs. Most of the data are taken from the older Field Manual FM 3-9 (1990). The expert may find that some of the data are only estimated, but not indicated as such. Only the details of GV-4 alias EA-5414 (CAS RN 158847-17-7) and GP/GV alias EA-5365 (CAS RN 141102-74-1) are new revelations to the public.

The Novichok class of chemical warfare agents belongs to those organophosporus compounds containing also a dihaloformaldoxime group: -O-N=C(X)Y group (X,Y = Cl, F, Br or even stable pseudohalogens such as C#N). Two examples of Novichok compounds are
a) Smiles: P(F)(=O)(O\N=C(/Cl)F)OCCCl with CAS RN 26102-97-6 and
b) Smiles: F/C(Cl)=N\OP(=O)(OCC)N(C)CCCl with CAS RN 26102-99-8
as published in Kruglyak, Yu. L.; Malekin, S. I.; Leibovskaya, G. A.; Khromova, Z. I.; Sretenskaya, I. I.; Martynov, I. V.: Reaction of alpha-chloronitrosoalkanes with phospholanes and iminophosphites, Khim. Primen. Fosfororg. Soedin., Tr. Konf., 4th (1972), Meeting Date: 1969, p. 307-312. Editor: Grechkin, N. P. Publisher: Nauka, Moscow, USSR. In fact the group of Novichok CWAs is quite large and it would be difficult to protect soldiers and civil personnel, when many different chemicals belonging this class of CWA could be used in chemical warfare with rogue nations or terrorists.

Several Russian chemists as P.P. Kirpichev, R.K. Bal'chenko, I.V. Martynov, Yu.A. Kruglyak, S.I. Malekin, and N.F. Privezentseva from the Moscow institutes GosNIIOKhT and INEOS developed
the principle of these extremely toxic OP haloformaldoximes already during the mid 60's. Rapid progress toward supertoxic variants was seen in the early 70's and the synthesis details were indeed published mainly in the Journal of General Chemistry (Zhurnal Obshchei Khimii), although absolutely no toxicity data of the Novichoks were revealed. All activities were covered as research for pesticides at that time. All publication activities of these authors ceased at the end of 1972.

Michael Crichton alias John Lange published in 1972 the thriller "Binary" which alarmed Russian politicians and military personnel to act quickly on the looming threat of US binary chemical weapons. In 1973 the further activities in the USSR under the new Foliant program were disguised again as a pesticide research program but kept secret until 1986 when some of the researches could publish more details about chemical and biological effects of phosphorylated oximes (e.g. Raevskii, 0. A.; Chapysheva, N. V.; Ivanov, A. N.; Sokolov, V. B.; Martynov, I. V., Effect of alkyl substituents in phosphorylated oximes, Zhurnal Obshchei Khimii (1987), 57(12), 2720-2723 and Raevskii, O. A.; Grigor'ev, V. Yu.; Solov'ev, V. P.; Ivanov, A. N.; Sokolov, V. B.; Martynov, I. V., Electron-donor functions of ethyl methylchloroformimino methylphosphonate, Zhurnal Obshchei Khimii (1987), 57(9), 2073-8)). It became clear that Novichoks do resist strongly poisoned Acetylcholinesterase/Butyrylcholinesterase reactivation by other common oximes (e.g. 2-PAM/EA-2170, TMB-4/EA-1814) as used so far by the American military forces. The final details to US authorities were given by Vil S. Mirzayanov alias Kenneth (Ken) Alibek who was responsible to detect any Novichok traces in the environment of the GosNIIOKhT branch no. 4 (CWA plant for Novichok) at Vol'sk-17 by gas chromatography. He, as an long standing expert in gas chromatography having the details of what he had to look for in the analyses defected to the US in 1992.

Since the beginning of the 90's US chemical demilitarization programs in the former GUS also included joint research on Novichoks. Now in order to develop effective detectors, detoxifiers, reactivators and bioscavengers (including BuChE). All such programs were named under activities versus "Fourth Generation Agents" (FGA) or "Non-Traditional Agents" (NTA). It seems each year is now coming up with a new disguising term in order not to use "Novichok" in public US documents. "Dusty agents" are also not covered in Ellison's handbook but should be seen in conjunction with the Novichok developments during the 70's and 80's. The Russian researchers V.A. Pasechnik, O.I. Stuzhuk, and Ye.A. Gayev contributed to this development. O.I. Stuzhuk proposed special minerals and diatoms for being contaminated with CWAs, whereas Ye. A. Gayev developed the physical CWA spraying/aerosol system and V.A. Pasechnik contributed to the development and application of "dusty agents" containing biological weapons.


More details would be fine, November 16, 2003
Reviewer: Anatoly Kuntsevich (Moscow, Russia) - See all my reviews
Although this book does not reveal the precise chemical formulas for the Novichok class of nerve agents it introduces into the hidden world of russian chem-bio weapon designers. The intelligence still fears to make public that Novichoks belong to organophosporus compounds containing the double halogenated oxime like -O-N=C(F)Cl group and that beside P.P.Kirpichev also I.V.Martnov and Yu.A.Kruglak from GosNIOKhT developed the principle of these extremely toxic OP oximes during the mid 60's already (and published also) which resist reactivation by other oximes. These chemicals an be made by heating only of substituted 1,3,2-dioxaphospholanes indicated slighly in this book. Hopefully int'l organizations will make public more details for the protection of other citizens than just army soldiers soon. (Review for Cassidy's Run: The Secret Spy War over Nerve Gas (Thorndike Press Large Print Core Series) [LARGE PRINT] )

MrSamosa
April 10th, 2005, 08:42 PM
Curse censorship, but thank God for Google caches and cheap websites who copy reviews from Amazon.com :) . Fear not Mega, all is not lost. But it is being lost faster than I thought... I used to find copies of that review all over Google, but the numbers are dwindling. So for safe-keeping, I'll put the original reviews right here in this thread; as you will see, most of my editing was for the sake of clarity--fixing grammar, rewording sentences, adding pictures.

Novichok(s), dusty agents and GV/GP agents, December 14, 2003
Reviewer: Anatoly Kuntsevich from Moscow, Russia
Although this book is missing the chemistry of the Novichok class of nerve agents it summarizes the physico-chemical data of the known CWAs. Most of the data are taken from the older Field Manual FM 3-9 (1990). The expert may find that some of the data are only estimated, but not indicated as such. Only the details of GV-4 alias EA-5414 (CAS RN 158847-17-7) and GP/GV alias EA-5365 (CAS RN 141102-74-1) are new revelations to the public.

The Novichok class of chemical warfare agents belongs to those organophosporus compounds containing also a dihaloformaldoxime group: -O-N=C(X)Y group (X,Y = Cl, F, Br or even stable pseudohalogens such as C#N). Two examples of Novichok compounds are
a) Smiles: P(F)(=O)(O\N=C(/Cl)F)OCCCl with CAS RN 26102-97-6 and
b) Smiles: F/C(Cl)=N\OP(=O)(OCC)N(C)CCCl with CAS RN 26102-99-8
as published in Kruglyak, Yu. L.; Malekin, S. I.; Leibovskaya, G. A.; Khromova, Z. I.; Sretenskaya, I. I.; Martynov, I. V.: Reaction of alpha-chloronitrosoalkanes with phospholanes and iminophosphites, Khim. Primen. Fosfororg. Soedin., Tr. Konf., 4th (1972), Meeting Date: 1969, p. 307-312. Editor: Grechkin, N. P. Publisher: Nauka, Moscow, USSR. In fact the group of Novichok CWAs is quite large and it would be difficult to protect soldiers and civil personnel, when many different chemicals belonging this class of CWA could be used in chemical warfare with rogue nations or terrorists.

Several Russian chemists as P.P. Kirpichev, R.K. Bal'chenko, I.V. Martynov, Yu.A. Kruglyak, S.I. Malekin, and N.F. Privezentseva from the Moscow institutes GosNIIOKhT and INEOS developed
the principle of these extremely toxic OP haloformaldoximes already during the mid 60's. Rapid progress toward supertoxic variants was seen in the early 70's and the synthesis details were indeed published mainly in the Journal of General Chemistry (Zhurnal Obshchei Khimii), although absolutely no toxicity data of the Novichoks were revealed. All activities were covered as research for pesticides at that time. All publication activities of these authors ceased at the end of 1972.

Michael Crichton alias John Lange published in 1972 the thriller "Binary" which alarmed Russian politicians and military personnel to act quickly on the looming threat of US binary chemical weapons. In 1973 the further activities in the USSR under the new Foliant program were disguised again as a pesticide research program but kept secret until 1986 when some of the researches could publish more details about chemical and biological effects of phosphorylated oximes (e.g. Raevskii, 0. A.; Chapysheva, N. V.; Ivanov, A. N.; Sokolov, V. B.; Martynov, I. V., Effect of alkyl substituents in phosphorylated oximes, Zhurnal Obshchei Khimii (1987), 57(12), 2720-2723 and Raevskii, O. A.; Grigor'ev, V. Yu.; Solov'ev, V. P.; Ivanov, A. N.; Sokolov, V. B.; Martynov, I. V., Electron-donor functions of ethyl methylchloroformimino methylphosphonate, Zhurnal Obshchei Khimii (1987), 57(9), 2073-8)). It became clear that Novichoks do resist strongly poisoned Acetylcholinesterase/Butyrylcholinesterase reactivation by other common oximes (e.g. 2-PAM/EA-2170, TMB-4/EA-1814) as used so far by the American military forces. The final details to US authorities were given by Vil S. Mirzayanov alias Kenneth (Ken) Alibek who was responsible to detect any Novichok traces in the environment of the GosNIIOKhT branch no. 4 (CWA plant for Novichok) at Vol'sk-17 by gas chromatography. He, as an long standing expert in gas chromatography having the details of what he had to look for in the analyses defected to the US in 1992.

Since the beginning of the 90's US chemical demilitarization programs in the former GUS also included joint research on Novichoks. Now in order to develop effective detectors, detoxifiers, reactivators and bioscavengers (including BuChE). All such programs were named under activities versus "Fourth Generation Agents" (FGA) or "Non-Traditional Agents" (NTA). It seems each year is now coming up with a new disguising term in order not to use "Novichok" in public US documents. "Dusty agents" are also not covered in Ellison's handbook but should be seen in conjunction with the Novichok developments during the 70's and 80's. The Russian researchers V.A. Pasechnik, O.I. Stuzhuk, and Ye.A. Gayev contributed to this development. O.I. Stuzhuk proposed special minerals and diatoms for being contaminated with CWAs, whereas Ye. A. Gayev developed the physical CWA spraying/aerosol system and V.A. Pasechnik contributed to the development and application of "dusty agents" containing biological weapons.


More details would be fine, November 16, 2003
Reviewer: Anatoly Kuntsevich (Moscow, Russia) - See all my reviews
Although this book does not reveal the precise chemical formulas for the Novichok class of nerve agents it introduces into the hidden world of russian chem-bio weapon designers. The intelligence still fears to make public that Novichoks belong to organophosporus compounds containing the double halogenated oxime like -O-N=C(F)Cl group and that beside P.P.Kirpichev also I.V.Martnov and Yu.A.Kruglak from GosNIOKhT developed the principle of these extremely toxic OP oximes during the mid 60's already (and published also) which resist reactivation by other oximes. These chemicals an be made by heating only of substituted 1,3,2-dioxaphospholanes indicated slighly in this book. Hopefully int'l organizations will make public more details for the protection of other citizens than just army soldiers soon. (Review for Cassidy's Run: The Secret Spy War over Nerve Gas (Thorndike Press Large Print Core Series) [LARGE PRINT] )

simply RED
April 13th, 2005, 06:56 AM
Quite impressive !
by the way...
I found genuine military toxicology report (Varshava pact) from 1971.
Novichok is not lised but anyway.
Hope will be interesting.
translation of the interesting part :

" We managed to test VX series contaning sulphur or nitrogen but not
holine part. They found out to be 10 to 100 times more toxic than normal VX gas even without fluorine in their molecules.
Normal VX (methylfluorophosphorylholine LD50 = 0,1 mg/kg )

Samples included:
GD-7

(C2H50)(CH3)(P=O)-S-CH2-CH2-S-C2H5

GD-42

(C2H50)(CH3)(P=O)-S-CH2-CH2-(S+)(CH3)(C2H5) SO4CH3(-)
LD50 = 0,032 mg/kg

We tested organophosphorous sulphur comatining series (proposed by K. Los)

Samples included

Compound-2

(CH30)2(P=O)-S-CH2-CH2-S(+)(CH3)(C2H5)
LD 50 = 0,07 mg/kg

Compound-4

(C2H50)2(P=O)-S-CH2-CH2-S(+)(C2H5)(C2H5)
LD50 = 0,01 mg/kg
{{{{{simple isn't it !!!}}}}}

EDEMO

O-ethyl-S-/2-diethylaminoethyl/methylthiophosphonate
LD 50 = O,02 mg/kg
And other compounds. {{{{{{not listed!!! sh**!!!}}}}}

We estimated 0,1-1 mg to be the absolute lethal dose (inhalation) for human of the new VX series.
VX gas "MEDETFK" was absolutely always lethal (animal - Cat) in dose 0,03 mg/kg.
We estimated binary reagents could be prepared by mixing

Compund 1
(CH30)2(P=O)-S-CH2-CH2-S-C2H5
LD = 65 mg/kg {{{{ yes sixtyfive, like dimethoate or lambda cyhalothrine }}}}
with dimethylsulphate :
{{{{ Reaction written by me
(CH30)2(P=O)-S-CH2-CH2-S-C2H5 + (CH30)2SO2 =
(CH30)2(P=O)-S-CH2-CH2-S(+)(CH3)(C2H5) CH3SO4(-)
LD = 0,07 mg/kg }}}}

Replacing sulphur with oxygen in any parts lowers the toxicity 1000 times.
{{{{{ this is about nerve gasses }}}}}
............................................

Our next goal is to test "crabaminoylcholinechloride" and "fluoroglucine"
{{{{{ translated 1:1 as they were misspelled }}}}}
for which we have intelligence data to be "tried" by the americans .


Somebody know how to prepare compound 1 ? :)

simply RED
April 13th, 2005, 06:56 AM
Quite impressive !
by the way...
I found genuine military toxicology report (Varshava pact) from 1971.
Novichok is not lised but anyway.
Hope will be interesting.
translation of the interesting part :

" We managed to test VX series contaning sulphur or nitrogen but not
holine part. They found out to be 10 to 100 times more toxic than normal VX gas even without fluorine in their molecules.
Normal VX (methylfluorophosphorylholine LD50 = 0,1 mg/kg )

Samples included:
GD-7

(C2H50)(CH3)(P=O)-S-CH2-CH2-S-C2H5

GD-42

(C2H50)(CH3)(P=O)-S-CH2-CH2-(S+)(CH3)(C2H5) SO4CH3(-)
LD50 = 0,032 mg/kg

We tested organophosphorous sulphur comatining series (proposed by K. Los)

Samples included

Compound-2

(CH30)2(P=O)-S-CH2-CH2-S(+)(CH3)(C2H5)
LD 50 = 0,07 mg/kg

Compound-4

(C2H50)2(P=O)-S-CH2-CH2-S(+)(C2H5)(C2H5)
LD50 = 0,01 mg/kg
{{{{{simple isn't it !!!}}}}}

EDEMO

O-ethyl-S-/2-diethylaminoethyl/methylthiophosphonate
LD 50 = O,02 mg/kg
And other compounds. {{{{{{not listed!!! sh**!!!}}}}}

We estimated 0,1-1 mg to be the absolute lethal dose (inhalation) for human of the new VX series.
VX gas "MEDETFK" was absolutely always lethal (animal - Cat) in dose 0,03 mg/kg.
We estimated binary reagents could be prepared by mixing

Compund 1
(CH30)2(P=O)-S-CH2-CH2-S-C2H5
LD = 65 mg/kg {{{{ yes sixtyfive, like dimethoate or lambda cyhalothrine }}}}
with dimethylsulphate :
{{{{ Reaction written by me
(CH30)2(P=O)-S-CH2-CH2-S-C2H5 + (CH30)2SO2 =
(CH30)2(P=O)-S-CH2-CH2-S(+)(CH3)(C2H5) CH3SO4(-)
LD = 0,07 mg/kg }}}}

Replacing sulphur with oxygen in any parts lowers the toxicity 1000 times.
{{{{{ this is about nerve gasses }}}}}
............................................

Our next goal is to test "crabaminoylcholinechloride" and "fluoroglucine"
{{{{{ translated 1:1 as they were misspelled }}}}}
for which we have intelligence data to be "tried" by the americans .


Somebody know how to prepare compound 1 ? :)

simply RED
April 13th, 2005, 06:56 AM
Quite impressive !
by the way...
I found genuine military toxicology report (Varshava pact) from 1971.
Novichok is not lised but anyway.
Hope will be interesting.
translation of the interesting part :

" We managed to test VX series contaning sulphur or nitrogen but not
holine part. They found out to be 10 to 100 times more toxic than normal VX gas even without fluorine in their molecules.
Normal VX (methylfluorophosphorylholine LD50 = 0,1 mg/kg )

Samples included:
GD-7

(C2H50)(CH3)(P=O)-S-CH2-CH2-S-C2H5

GD-42

(C2H50)(CH3)(P=O)-S-CH2-CH2-(S+)(CH3)(C2H5) SO4CH3(-)
LD50 = 0,032 mg/kg

We tested organophosphorous sulphur comatining series (proposed by K. Los)

Samples included

Compound-2

(CH30)2(P=O)-S-CH2-CH2-S(+)(CH3)(C2H5)
LD 50 = 0,07 mg/kg

Compound-4

(C2H50)2(P=O)-S-CH2-CH2-S(+)(C2H5)(C2H5)
LD50 = 0,01 mg/kg
{{{{{simple isn't it !!!}}}}}

EDEMO

O-ethyl-S-/2-diethylaminoethyl/methylthiophosphonate
LD 50 = O,02 mg/kg
And other compounds. {{{{{{not listed!!! sh**!!!}}}}}

We estimated 0,1-1 mg to be the absolute lethal dose (inhalation) for human of the new VX series.
VX gas "MEDETFK" was absolutely always lethal (animal - Cat) in dose 0,03 mg/kg.
We estimated binary reagents could be prepared by mixing

Compund 1
(CH30)2(P=O)-S-CH2-CH2-S-C2H5
LD = 65 mg/kg {{{{ yes sixtyfive, like dimethoate or lambda cyhalothrine }}}}
with dimethylsulphate :
{{{{ Reaction written by me
(CH30)2(P=O)-S-CH2-CH2-S-C2H5 + (CH30)2SO2 =
(CH30)2(P=O)-S-CH2-CH2-S(+)(CH3)(C2H5) CH3SO4(-)
LD = 0,07 mg/kg }}}}

Replacing sulphur with oxygen in any parts lowers the toxicity 1000 times.
{{{{{ this is about nerve gasses }}}}}
............................................

Our next goal is to test "crabaminoylcholinechloride" and "fluoroglucine"
{{{{{ translated 1:1 as they were misspelled }}}}}
for which we have intelligence data to be "tried" by the americans .


Somebody know how to prepare compound 1 ? :)

akinrog
April 13th, 2005, 08:05 AM
Compound 4 seems dubious to me.

(C2H50)2(P=O)-S-CH2-CH2-S(+)(C2H5)(C2H5)
LD50 = 0,01 mg/kg

How Sulfur may have three bonds (like -S(+)(C2H5)(C2H5))?

Maybe a typo if sulfur is nitrogene then everything fits and we have VX :)

akinrog
April 13th, 2005, 08:05 AM
Compound 4 seems dubious to me.

(C2H50)2(P=O)-S-CH2-CH2-S(+)(C2H5)(C2H5)
LD50 = 0,01 mg/kg

How Sulfur may have three bonds (like -S(+)(C2H5)(C2H5))?

Maybe a typo if sulfur is nitrogene then everything fits and we have VX :)

akinrog
April 13th, 2005, 08:05 AM
Compound 4 seems dubious to me.

(C2H50)2(P=O)-S-CH2-CH2-S(+)(C2H5)(C2H5)
LD50 = 0,01 mg/kg

How Sulfur may have three bonds (like -S(+)(C2H5)(C2H5))?

Maybe a typo if sulfur is nitrogene then everything fits and we have VX :)

megalomania
April 15th, 2005, 05:49 PM
It has occured to me that a little social networking is in order to track down all possible scientific articles about Novichok agents and chemical weapons in general. Thanks to the papers provided by Samosa and Fritz I have used the names of the authors in those articles as a basis for a search for all of their respective articles.

The theory is whoever publishes an article about a chemical weapon has probably published other articles on chemical weapons. The theory also stipulates whoever he co-authored these papers with also probably work in chemical weapons, so their articles are likely to be related to chemical weapons research.

The end result is I have nearly 1000 articles published by the top dozen names, leading me to dozens more authors. I now have to sift through the first batch of all the articles to weed out any unrelated publications, and to find out who the co-authors of the good articles are.

I also read a tidbit in Tobiasons Scientific Principles, the chemical weapons volume, that the Soviets intentionally published large amounts of chemical weapons information in the open literature in the 1950s and 1960s with the hope some rogue nation would use the information to attack the US. The goal here was for the rogue state to finish the job for the Soviet Union, or at least inflict massive American casualities. Now all I need to do is find out what journals they published this stuff in. Zhurnal Obshchei Khimii is probably a good place to start since it has an English translation.

Also, in the paper by Mr Samosa the molecular structures for the two examples of Novichok compounds are incorrect. I donít know if the CAS numbers are wrong for the right structures, or if the structures are wrong for the right CAS number. I think the wrong structures were used for the right CAS numbers.
(see attached image)

One name that seems to pop up a lot is I. V. Martynov. He has published about 500 journal articles in his lifetime to date. Indeed there are many about phosphorus compounds, but those type of articles cease after 1972. He publishes many articles about molecular refraction after that. In 1984 he resumes publication of phosphorus related articles.

One article in particular caught my eye:
Synthesis and anticholinesterase activity of fluorochloronitroacetic acid esters. Ivanov, Yu. Ya.; Brel, V. K.; Postnova; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1985), 19(8), 968-71.

There are a few earlier articles about fluorochloronitroacetic acid esters. These are important in the systhesis of Novichoks I would imagine. Samosa did mention in his paper (NovDAGVGP.doc attached earlier) that dihaloformaldoxime are critical parts of Novichok agents, and fluorochloronitroacetic acid should form those.

Another article Martynov published related to bicyclic phosphates. There is another thread Samosa started about those. I donít know enough about them to say if this article is of interest. The abstract mentions this compound is a chloride blocker, it blocks GABA-independent Cl- channels specificially. Perhaps someone with knowledge of biology can say if blocking those is lethal. The article is:
4-Methyl- and 4-ethylbicyclophosphates, blockers of chloride channels. Fetisov, V. I.; Redkozubov, A. E.; Lyubimov, V. S.; Sokolov, V. S.; Martynov, I. V.. USSR. Biologicheskie Membrany (1986), 3(9), 968-70.
4-Methyl- (I; R = Me) [1449-89-4] and 4-ethylbicyclophosphate (I; R = Et) [1005-93-2] were effective blockers of GABA-independent Cl- channels (of Limnaea stagnalis giant neurons). Both potential and thermoregulation of the Cl- channels were affected.


Here is another article of potential use in the preparation of Novichok agents. This compound is similar to fluorochloronitroacetic acid from which this substance is made:
Synthesis of chlorofluoronitronitrosomethane. Martynov, I. V.; Brel, V. K.; Uvarova, L. V. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1986), (4), 952-3.
Decarboxylation-nitrosation of ClFC(NO2)CO2H with HNO3 gave 52% ClFC(NO)NO2

Here is another possible tidbit as it relates to insecticides and plant growth regulation. We know they disguised their research under the guise of agrichemicals:
Synthesis and pesticidal activity of chloronitroacetic acid esters. Martynov, I. V.; Yurtanov, A. I.; Ivanov, Yu. J.; Kulish, E. V.; Uvarova, L. V.; Andreeva, E. I.; Rozhkova, N. G.; Zhirmunskaya, N. M. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1986), 289(1), 109-13 [Chem.].
A series of 31 O2NCRR1CO2R [e.g., R, R1, R2 = H, Cl, n-C7H15 (I); F, Cl, ClCH2CH2; Br, Cl, Et] was tested for insecticidal and, in some cases, plant growth regulatory activity. Eight of the compds., e.g., I, were active insecticides. Twelve of the compds. were new but no prepn. details were given.

Here is another possible Novichok variant:
Reaction of phosphorus trichloride with 1,1,2-trichloro-1-nitrosoethane in sulfur dioxide. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1986), (9), 2158.
Reaction of ClCH2CCl2NO with PCl3 in SO2 gave 58% ClCH2CCl:NOP(O)Cl2.


Here is yet another possible Novichok variant:
Reaction of dialkyl phosphites with 1,1-dichloronitrosoalkanes. Ivanov, A. N.; Epishina, T. A.; Goreva, T. V.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (1), 226-8.
(RO)2P(O)ON:CClR1 (R = Bu, Me2CHCH2, pentyl, Me, Et; R1 = Me, Et, Pr, Me2CH, Bu, Me2CHCH2) were prepd. in 44-67% yields by treating (RO)2POH with ONCCl2R1 in EtOH at 20.

Here is a toxicity study done on animals and humans for some pesticides. Yeah, pesticides, thatís the ticket:
Delayed neurotoxicity from organophosphorus pesticides. Makhaeva, G. F.; Malygin, V. V.; Martynov, I. V.. USSR. Agrokhimiya (1987), (12), 103-24.
A review with 123 refs. on 8 clin. intoxication symptoms, pathmorphol., mechanisms of initiation of delayed neurotoxicity by organophosphorus pesticides (OPP) structure-activity relations of OPP, monitoring of the delayed neurotoxicity of OPP in animals and humans, etc.

Here is another possible Novichok variant:
Reaction of O-alkyl methylphosphonites with 1,1-dichloro-1-nitrosopropane. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(4), 952-3.
Reaction of ROP(O)HMe (R = Me2CH, Bu, pentyl) with EtCCl2NO in Et2O gave 50-52% ROP(O)MeON:CClEt (I; same R). Treating MeP(OR)2 with EtCCl2NO also gave I.

Here is an interesting reference, although I doubt this would have very high human toxicity due to the two large aryl groups attached to phosphorus. Still, it gives enlightenment as to where they are headed:
Reaction of diphenylphosphinous acid with 1,1-dichloro-1-nitrosoalkanes. Sokolov, V. B.; Epishina, T. A.; Ivanov, A. N.; Kharitonov, A. V.; Brel, V. K.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(7), 1658-9.
Treating Ph2P(O)H with RCCl2NO (R = Et, Pr, Me2CH) in Et2O gave 62-75% Ph2P(O)ON:CClR (same R).


Another Novichok possibility:
Synthesis and the structure of dialkylfluoroformiminophosphates. Martynov, I. V.; Brel, V. K.; Uvarov, V. I.; Yarkov, A. V.; Novikov, V. P.; Chepakova, L. A.; Raevskii, O. A. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (4), 857-60.
Syn- And anti-(RO)2P(O)N:CHF (R = Me, Et, Pr, Bu) were prepd. in 11-25% yields by treating (RO)3P with ClCHFNO2.

Here is some nasty looking stuff that may be of interest:
Reaction of (-aminoalkyl)phosphonates with perfluoro-2-azapropene. Aksinenko, A. Yu.; Pushin, A. N.; Sokolov, V. B.; Gontar, A. F.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (5), 1177-9.
(RO)2P(O)CMeR1N:C:NCF3 (R = Me, R1 = Et; R = Et, R1 = Et, Pr, Bu; R = Me2CHCH2, R1 = Et) were prepd. in 40-60% yields by condensing CF2:NCF3 with (RO)2P(O)CMeR1(NH2) in the presence of KF.

Here is another variant:
Reaction of polychloronitrosoethanes with phosphorous acid derivatives. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (5), 1086-9.
The title reaction gave 20-93% of 22 o-phosphorylated alkyl chloroformimines. Thus, treating ONCCl2R (R = Me, CH2Cl, CHCl2) with (R1O)3P (R1 = Me, Pr, Bu, Me2CHCH2, pentyl, ClCH2CH2) gave (R1O)2P(O)ON:CClR.

Of all the other compounds I have previously referenced this particular compound looks like it may be the deadliest. It has some similarities to most other nerve gasses in that it uses the simplest alkyl groups, and has a direct alkyl and a direct halogen attachment to phosphorus. I would replace those chlorines with fluorine to increase the toxicity:
Reaction of dichloromethylphosphine with 1,1-dichloro-1-nitrosoalkanes. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(7), 1659-60.
MePCl2 reacted with RCCl2NO (R = Et, Pr, Me2CH) in SO2 to give 27-37% RCCl:NOP(O)ClMe.

This compound looks like a good precursor for organophosphorus agents like the previous compound. The chlorines can be replaced by F, and one of the fluorines can form an ester or something else. The second compound is an example of what could be made, and I just bet that stuff is pretty toxic.
Interaction of 2,2,3,3-tetrafluoropropyl dichlorophosphite with 1,1,2-trichloro-1-nitrosoethane. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (6), 1422-3.
Refluxing CHF2CF2CH2OPCl2 (I) with CH2ClCCl2NO (II) in Et2O gave 67.8% Cl2P(O)ON:CClCH2Cl. Treating I with II in SO2 at 20 gave 48.2% (CHF2CF2CH2O)ClP(O)ON:CClCH2Cl.

We might have a real winner with this one as it has similarities with VX nerve gas. The second compound in particular has a =S group. If that could be isomerized, like it is done in making VX, then we have a thioester. The two isobutyl groups are probably too large to make this particular compound all that toxic. I am sure they could be replaced with methyls instead.
Reaction of diisobutylchlorophosphine with 1,1-dichloro-1-nitrosoalkanes in presence of sulfur dioxide and ethyl mercaptan. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (11), 2586-8.
Treating (Me2CHCH2)2PCl with RCCl2NO (R = Me, Et, Pr, Me2CH) in Et2O contg. SO2 gave 61-74% (Me2CHCH2)2P(O)ON:CRCl (same R). When Et2SH was used instead of SO2, 44% (Me2CHCH2)2P(S)ON:CRCl (R = Me) was obtained.

Another phenyl attached compound:
Synthesis and molecular structure of (O-isopropylchloroformimino) diphenylphosphinate. Martynov, I. V.; Chekhlov, A. N.; Ivanov, A. N.; Epishina, T. A.; Makhaev, V. D.; Sokolov, V. B. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (11), 2595-7.
Treating Ph2PH with Me2CHCCl2NO in C6H6 gave 58% Ph2P(O)ON:CClCHMe2, the structure of which was detd. by x-ray crystallog.

This compound has some VX similarities too:
O,O-Dialkyl O-(dialkylformimino) thiophosphates. Chepakova, L. A.; Brel, V. K.; Pushin, A. N.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(12), 2716-19.
Twelve (R1O)2P(S)ON:CMeR (R = Me, Et, Pr; R1 = Me, Et, Pr, Bu) were prepd. in 41-62% yields by treating (R1O)2PHS with ONCClMeR or HON:CMeR.

These compounds are similar to the last journal reference except the R and Rí groups are switched. Isomerize that S and we may have something far more toxic.
O-(Alkylchloroformimino) O,O-dialkyl thiophosphates. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (12), 2854-5.
Seven (RO)2P(S)ON:CClR1 (R = Et, Me2CH; R1 = Me, Et, Pr, Me2CH, ClCH2) were prepd. in 33-54% yields by condensing (RO)2PSH with R1Cl2CNO in THF.

Martynov has 64 publications in 1988 alone, his best year. In no particular order here are some highlights:

Molecular and crystal structure of O,O-diethyl 1-[N2-(trifluoromethyl)fluoroformamidino]-1-methylethylphosphonate. Chekhlov, A. N.; Aksinenko, A. Yu.; Sokolov, V. B.; Korenchenko, O. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1988), 302(4), 855-8 [Chem.].
The crystal and mol. structure of (EtO)2P(O)CMe2NHCFNCF3 was detd.

Reaction of (N-acetyl-N-ethylamido)alkylphosphonic acid chlorides with cesium fluoride. Krolevets, A. A.; Adamov, A. V.; Popov, A. G.; Martynov, I. V.. USSR. Zhurnal Obshchei Khimii (1988), 58(11), 2628-9.
RP(O)F(NEtCH:CH2) (R = Me, Me2CH) were prepd. in 45, 50% yields, resp., by treating RPCl(NEtAc) (I) with CsF. I were prepd. in 60, 65% yields, resp., by treating RPCl2 with Me3SiNEtAc.

Stable alkoxyfluorophosphoranes. Krolevets, A. A.; Popov, A. G.; Adamov, A. V.; Martynov, I. V.. USSR. Zhurnal Obshchei Khimii (1988), 58(11), 2626-7.
RPF2(OR1)2 (R = BuCHClCH2, R1 = Me3C; R = Me2CClCH2, R1 = Et) were prepd. in 45, 40% yields, resp., by treating RPF4 with Me3SiOR1.

O-(Alkylchloroformimidoyl) o-alkyl methylphosphonates. Sokolov, V. B.; Ivanov, A. N.; Goreva, T. V.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (5), 1128-30.
Nine (RO)MeP(O)ON:CClR1 (R = Et, Pr, Bu, Me2CH, pentyl; R1 = Me, Et, Pr, Bu, Me2CH) were prepd. in 41-67% yields by treating R1CCl2NO with MeP(OR)2 or MeP(O)H(OR).

Reaction of 1,1-dichloro-1-nitrosoalkanes with phosphorus(III) chlorides. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (9), 2128-32.
The title reaction was studied. Thus, R1R2P(O)ON:CRCl (R = Me, Et, Pr, Me2CH; R1 = R2 = Cl, Me2CHCH2; R1 = Cl, R2 = Me) were prepd. in 34-74% yields by reaction of RCCl2NO with R1R2PCl in the presence of SO2.

Synthesis and x-ray diffraction study of N-(diisopropoxythiophosphoryl)thioacetamide. Solov'ev, V. N.; Chekhlov, A. N.; Zabirov, N. G.; Cherkasov, R. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1988), 300(6), 1386-9 [Chem.].
Treating MeCSNH2 with Me3COK in MeCN and then with ClP(S)(OCHMe2)2 gave 15% MeCSNHP(S)(OCHMe2)2, the structure of which was detd. by x-ray crystallog.

Reaction of 1,1-dichloro-1-nitrosoethane with phosphorus oxychloride in the presence of zinc. Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (7), 1691.
Cl2P(O)ON:CClMe was prepd. in 26.6% yield by treating MeCCl2NO with POCl3 in the presence of Zn.

Comparative studies on the interaction of acetylcholinesterases from human erythrocytes and housefly heads with phosphorylated alkylchloroformoxims. Shataeva, G. A.; Makhaeva, G. F.; Yankovskaya, V. L.; Sokolov, V. B.; Ivanov, A. N.; Martynov, I. V.. Inst. Physiol. Act. Subst., Chernogolovka, USSR. Zhurnal Evolyutsionnoi Biokhimii i Fiziologii (1988), 24(6), 791-6.
Among Valexon analogs, 6 (RO)2P(O)ON:CClMe (I), 6 (RO)2P(O)ON:C(Cl)CH2Cl (II), and 5 (RO)2P(O)ON:C(Cl)CHCl2 (III, R = Me, Et, Pr, iso-Bu, Bu, amyl), and 4 (EtO)2P(O)ON:C(Cl)R1 (IV, R1 = Me, Et, Pr, Bu), I-III (R = Et) were highly selective insecticides, having rate consts. of bimol. reaction with acetylcholinesterase (KII) of human erythrocytes (HE) lower by 1 magnitude order than with that from housefly heads (FL). Inhibition of both HE and FL followed the order I < II < III. Phosphorylation capacity of II 1.6-fold exceeded that of I. Replacing Me by Et, increased the effect of I-III on FL 3-8-fold and decreased that on HE 1.7-4-fold. Further increases in hydrophobicity abolished the specificity of I-III. The selectivity of IV decreased in order of R1: Me > Et > Bu; IV (R1 = Pr) showed no selectivity.

Fluorination of some phosphoric acid derivatives. Zavorin, S. I.; Lermontov, S. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka., USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (5), 1174-6.
Dialkyl fluorophosphates were prepd. by the title fluorination with Et3N.3HF (I). Thus, fluorination of (EtO)2P(O)ON:CCl2 with I in MeCN gave 83.5% (EtO)2P(O)F.

Reaction of fluorine-containing acetylenic alcohols with phosphorus trichloride. Brel, V. K.; Chekhlov, A. N.; Ionin, B. I.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1988), 58(4), 750-7.
Treating RC.tplbond.CCMe(OH)CH2F (I; R = Ph) with PCl3 in Et2O gave 45% Cl2P(O)CR:C:CMeCH2F (II; R = Ph) and 24% E- and Z-Cl2P(O)CHPhCCl:CMeCH2F (III). Under the same conditions, I (R = MeOCH2) gave a mixt. of II (R = MeOCH2) and Cl2P(O)C(:CH2)CCl:CMeCH2F. Treating I (R = Ph) with MeOH and then with Br2 gave oxaphospholene IV. The structure of III was detd. by x-ray crystallog.

Synthesis and anticholinesterase activity of fluorochloronitroacetic acid thioesters. Ivanov, Yu. Ya.; Uvarov, V. I.; Brel, V. K.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1988), 22(5), 538-40.
Treating O2NCFClCOX (I; X = OH) with PCl5 gave I (X = Cl), which reacted with RSH (R = Et, Bu) to give 35-55% I (X = SR; same R) (II). II were less effective acetylcholinesterase inhibitors than I (X = OR; same R) but had comparable activity vs. butyrylcholinesterase with lower toxicity.

Synthesis and antiesterase activity of sulfur-containing phosphorylated oximes. Chepakova, L. A.; Bret, V. K.; Makheva, G. F.; Yankovskaya, V. L.; Beznosko, B. K.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1988), 22(2), 143-6.
Reaction of (RS)2POEt (R = Et, Pr, iso-Bu, Bu or amyl) with O:NCFCl2 gave the corresponding (RS)2P(:O)ON:CClF (I). An increase in the hydrophobicity of I did not alter the anticholinesterase activity of I, while the butyrylcholinesterase and carboxylesterase activity were increased.

O-substituted alkylchloroformoximes as substrates and inhibitors of cholinesterases. Ivanov Iu Ia; Sokolov V B; Epishina T A; Martynov I V Doklady Akademii nauk SSSR (1990), 310(5), 1253-5.

Inhibition of cholinesterase activity with fluorine-containing derivatives of alpha-aminophosphonic acid. Kuusk V V; Morozova I V; Agabekian R S; Aksinenko A Iu; Epishina T A; Sokolov V B; Kovaleva N V; Razdol'skiy A N; Fetisov V N; Martynov I V Bioorganicheskaia khimiia (1990 Nov), 16(11), 1500-8.
A series of O,O-diethyl-1-(N-alpha-hydrohexafluoroisobutyryl)aminoalkylphos phonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate constants and the enzyme-inhibitor intermediate dissociation constants are calculated. The quantitative structure-activity relationships including both hydrophobic and calculated steric parameters of substituents are developed for APh--ChE interactions. Molecular mechanics (programme MM2) was used for determining steric parameters (Es). On the basis of QSAR models analysis it was concluded that hydrophobic interactions play an essential role in APh--AChE binding, whereas for APh--BuChE binding steric interactions are essential. Presence of at least two APh binding centres on the surface of AChE and BuChE is suggested.

Reaction of 1,1-dichloro-1-nitrosobutane with (N,N-dimethylamido)dichlorophosphite. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (6), 1416-18.
Reaction of PrCCl2NO with Me2NPCl2 in Et2O or in SO2 gave 36% Me2NPCl4 or 30% Me2NP(O)ClON:CClPr, resp. Treating Me2NPCl4 with SO2 gave 91% Me2NP(O)Cl2. Reaction of PrCCl2NO with Me2NPCl2 in Et2O, and then with Ph3P and distn. gave Ph3PO and PrCN.

Alkyl chlorofluoroformimino perfluoroalkylphosphonates. Chepakova, L. A.; Brel, V. K.; Martynov, I. V.; Maslennikov, I. G. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Zhurnal Obshchei Khimii (1989), 59(6), 1455-6.
Treating RP(OR1)2 (R = CF3, R1 = Pr, Bu; R = CF3CF2, R1 = Me, Bu) with CFCl2NO in Et2O gave 76-88% title compds. R1OP(O)RON:CFCl.

Synthesis of dialkyl (3-alkyl-1,3-alkadien-2-yl)phosphonates. Brel, V. K.; Abramkin, E. V.; Martynov, I. V.; Ionin, B. I. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1989), 59(9), 2142-3.
(RO)2P(O)C(:CH2)CR1:CMe2 (R = Et, Pr; R1 = Me, Et) were prepd. in 41-73% yields by the Grignard reaction of (RO)2P(O)C(CH2OMe):C:CMe2 with R1X (X = halo).

Synthesis and antiesterase activity of O,O-dialkyl S-(ethoxycarboxyl)chloromethyl thiophosphates. Khaskin, B. A.; Makhaeva, G. F.; Torgasheva, N. A.; Ishmuratov, A. S.; Yankovskaya, V. L.; Fetisov, V. I.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovko, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (12), 2741-6.
The title compds. (RO)2P(O)SCHClCO2Et (I; R = alkyl homologs) were prepd. in 82-95% yields in the reaction of (RO)2P(O)SCl with N2CHCO2Et at -25 (in Et2O) or 6-7 (in benzene), presumably via a noncarbene mechanism. I irreversibly inhibited acetylcholinesterase, butyrylcholinesterase, and carboxylesterase; antibutyrylcholinesterase activity increased in the homologous series of R, with max. at R = Bu. An antiesterase MSBAR of I was fulfilled with parameters representing hydrophobicity and steric properties of R.

Synthesis and cholinesterase hydrolysis of O-acylated alkylchloroformoximes. Sokolov, V. B.; Ivanov, Yu. Ya.; Epishina, T. A.; Agabekyan, R. S.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1989), 23(11), 1317-20.
The title compds., RCO2N:CClR1 (R = Me, Et, Pr or CH2Cl and R1 = Me, Et, Pr, or iso-Pr) were prepd. e.g., by the reaction of 1,1-dichloro-1-nitrosobutane with AcCl in the presence of Zn. These compds. were good substrates for acetyl- and butyrylcholinesterases. The kinetic parameters (Km, Vmax and ac) of these compds. in the hydrolysis reactions were comparable to those with acetylcholine. The acute toxicity was 79-381 mg/kg in mice given drugs orally.

Synthesis and structure of O,O-dialkyl 2-[(ethoxycarbonyl)amino]hexafluoroisopropylphosphonates. Aksinenko, A. Yu.; Chekhlov, A. N.; Korenchenko, O. V.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1990), 60(1), 61-5.
The title compds. (RO)2P(O)C(CF3)2NHCO2Et (I; R = Me, Et, CHMe2) were prepd. in 54-76% yields in the reaction of (RO)2P(O)H with (CF3)2C:NCO2Et. The crystal and mol. structure of I (R = Et) was detd.

O-Substituted alkylchloroformoximes as substrates and inhibitors of cholinesterases. Ivanov, Yu. Ya.; Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1990), 310(5), 1253-5 [Biochem.].
The ability of O-substituted alkylchloroformoximes to serve as substrates for acetylcholinesterase (ACE, EC 3.1.1.7) and butyrylcholinesterase (BCE, EC 3.1.1.8) and to inhibit acetylcholine hydrolysis by these enzymes was detd., along with the LD50 of these compds. in mice. The compds. tested were O-acylated alkylchloroformoximes of the general formula R1C(O)ON:C(Cl)R2 [R1 = R2 = Me; R1 = Me, R2 = Et; R1 = Me, R2 = Pr; R1 = Et, R2 = Me; R1 = Et, R2 = iso-Pr; R1 = Pr, R2 = iso-Pr; R1 = CH2Cl, R2 = Pr (I); R1 = CH2Cl, R2 = iso-Pr (II)], O-carbonylated alkylchloroformoximes of the general formula EtOC(O)ON:C(Cl)R [R = Me (III), iso-Pr (IV)], and O-carbamoylated alkylchloroformoximes of the general formula (Me)2NC(O)ON:C(Cl)R [R = Me (V), iso-Pr (VI)]. All of the compds. except for I and II were good substrates for the enzymes, with Km values for ACE ranging (0.3-11.0)  10-4M and for BCE ranging (0.5-13.0)  10-4M (the Km values of ACE and BCE with acetylcholine were 1.3  10-4 and 5.4  10-4M, resp.). III and IV were competitive (Ki 1.6  10-4M) and mixed-type (Ki 4.2  10-4M) inhibitors, resp., of ACE. V and VI were effective inhibitors of both ACE and BCE, with bimol. rate consts. for inhibition (kII) of 5.7  103 and 1.4  105 M-1 min-1, resp., for ACE, and 9.8  103 and 5.4  106 M-1 min-1, resp., for BCE. The LD50 values for the tested compds. ranged 60-381 mg/kg body wt.

O-(alkylchloroformimino)(methyl)thiophosphonic acid chlorides. Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (12), 2865-6.
Treating the adduct from RCCl2NO and MePCl2 with H2S gave 21-35% MeP(S)ClON:CRCl.

Interaction of 1,1-dichloro-1-nitrosoalkanes with S-ethylmethylphosphonous chloride in the presence of sulfur dioxide. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1990), (2), 464-5.
EtSP(O)MeON:CClR (R = Me, Et, Pr) were prepd. in 42-47% yields by treating RCCl2NO with EtSPMeCl in the presence of SO2.

O-(alkylchloroformimino)-O-alkylphosphoric acid chlorides. Sokolov, V. B.; Ivanov, A. N.; Goreva, T. V.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1990), (5), 1122-5.
Reaction of (ON)CCl2R with (R'O)2PCl (R, R' = alkyl) afforded the title compds. (R'O)ClP(O)ON:CRCl (I) in up to 69% yield. Hydrolysis of I led to substitution of P-, and not C-bound Cl, resulting in (R'O)(NH4O)P(O)ON:CRCl.

Reaction of the adduct of methyldichlorophosphine and 1,1-dichloro-1-nitrosoethane with thioacetic acid. Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1990), 60(8), 1923-4.
Treating MePCl2 with MeCCl2NO in PhMe, followed by addn of 1 or 2 equiv AcSH gave 56% MeP(S)ClON:CMeCl or 32% MeP(S)ClON:CMeSAc, resp.

Inhibition of cholinesterase activity by fluorine-containing derivatives of -aminoalkylphosphonic acids. Kuusk, V. V.; Morozova, I. V.; Agabekyan, R. S.; Aksinenko, A. Yu.; Epishina, T. A.; Sokolov, V. B.; Kovaleva, N. V.; Razdol'skii, A. N.; Fetisov, V. I.; Martynov, I. V.. Inst. Physiol. Act. Subst., Chernogolovka, USSR. Bioorganicheskaya Khimiya (1990), 16(11), 1500-8.
A series of O,O-diethyl-1-(N--hydrohexafluoroisobutyryl)aminoalkylphosphonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate consts. and the enzyme-inhibitor intermediate dissocn. consts. are calcd. The quant. structure-activity relationships including both hydrophobic and calcd. steric parameters of substituents are developed for APh-ChE interactions. Mol. mechanics (program MM2) was used for detg. steric parameters (Es). On the basis of QSAR models anal. it was concluded that hydrophobic interactions play an essential role in APh-AChE binding, whereas for APh-BuChE binding steric interactions are essential. Presence of at least two APh binding centers on the surface of AChE and BuChE is suggested.

Synthesis and anticholinesterase activity of O-carbamoylated alkylchloroform oximes. Sokolov, V. B.; Ivanov, Yu. Ya.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshestva, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1991), 25(4), 33-4.
Treating ClCO2N:CClR (R = Me, Et, Pr, CHMe2) with NHR1R2 (R1 = R2 = H, Me, Et; R1 = H, R2 = Me) in Et2O gave 50-69% R1R2NCO2N:CClR (same R-R3), which are acetyl- and butyrylcholinesterase inhibitors (k11 = 1.1  10-2 to 5.4  10-6 M-1 min-1). Acute oral toxicity in mice ranged from 32 to 565 mg/kg.

O-Alkyl O-methylchloroformimino phenylphosphonates - effective inhibitors of the hen brain neurotoxic esterase. Makhaeva, G. F.; Kononova, I. V.; Malygin, V. V.; Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1991), 317(4), 1009-12 [Biochem.].
The title phosphonates were effective inhibitors of neurotoxic esterase; with increasing hydrophobicity the compds. showed pronounced and selective biol. activity towards brain neurotoxic esterase compared to acetylcholinesterase. Thus, the structure of phenylphosphonate played a major role in the inhibitory effects of these potential pesticides towards neurotoxic esterase or acetylcholinesterase.

Synthesis and anticholinesterase activity of fluorine-containing -aminophosphoryl compounds. Korenchenko, O. V.; Ivanov, Yu. Ya.; Aksinenko, A. Yu.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Khimiko-Farmatsevticheskii Zhurnal (1992), 26(6), 21-3.
Reaction of R2P(O)H (R = MeO, EtO, PrO, Me2CHO, Ph) with (CF3)2C:NCOR1 (R1 = OEt, OCH2Ph, OPr, OBu, OCH2CH2CHMe2, CF3) in Et2O gave 44-93% R2P(O)C(CF3)2NHCOR1. Treating a 1,4,2-oxazaphospholine deriv. with alcs. gave Me(R)P(O)C(CF3)2NHCO2Et (R = BuO, Me2CHO). Bimol. rate consts. for inhibition of cholinesterases by these compds. were detd.

Synthesis and insecticidal and acaricidal activity of O-alkylchloroformimine O,O-dialkyl phosphates and O,O-dialkylthiophosphates. Ivanov, A. M.; Ivanova, G. B.; Sokolova, V. B.; Epishina, T. N.; Goreva, T. V.; Beznosko, B. K.; Martynov, I. V.. Inst. Fiziol. Okl. Veshchestv., Chernogolovka, Russia. Fiziologicheski Aktivnye Veshchestva (1991), 23 58-62.
Of 26 title compds., those having ethoxy group at P were both insecticides and acaricides, whereas those having their methoxy group showed insecticidal activity only. Increasing hydrophobicity of the alkoxy substituents decreased i.m. toxicity to mice, but also the effectiveness. O replacement by S also decreased toxicity. Synthesis is indicated.

Paradoxical toxic effect and calcium antagonism of the cholinesterase inhibitors O-(N-arylcarbamoyl)acylhydroximoyl chlorides. Ivanov, Yu. Ya.; Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Doklady Akademii Nauk (1993), 328(6), 744-6 [Biochem.].
N-phenylcarbamates and aliph. analogs of the formula R R1N(O)ON::C(Cl)R2 [where R = Et, Me, and Ph; R1 = H, Me; R2 = Et, Pr, iso-Pr] were examd. for their acetylcholinesterase and butyrylcholinesterase inhibition, for their acute toxicity and their action on selective organs. The enzyme inhibition depended on their mol. structure. Paradoxical effects (higher dose and low toxicity and vice versa) were noted.

Similar sensitivity of rat and hen brain neurotoxic esterase to inhibition by O-alkyl-O-alkylchloroformiminophenylphosphonates. Makhaeva, G. F.; Filonenko, I. V.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Doklady Akademii Nauk (1993), 332(5), 650-3.
Quant. structure-neurotoxic esterase (NTE)-inhibiting activity relationship of the title phosphonates was examd. against both rat and chicken enzyme. The phosphonates effectively inhibited the enzyme from both the sources. The anti-NTE activity of the compds. increased with the length of alkyl radical in the phosphoryl portion. The introduction of branched substituent, esp. in the -position, decreased the antienzyme activity. Math. equations are derived to describe the effects of steric factors on the NTE inhibition. PI50 = -lg I50, where I50 is the concn. of the inhibitor required to cause 50% inhibition, was calcd. for these compds.; the values are tabulated.

Crystal and molecular structures and synthesis of O,O-diisopentyl 1-(phenylsulfonamido)-1-(trifluoromethyl)-2,2,2-trifluoroethylphosphonate. Chekhlov, A. N.; Aksinenko, A. Yu.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Ross. Akad. Nauk, Chernogolovka, Russia. Doklady Akademii Nauk (1995), 345(3), 360-363.
Reaction of (CF3)2C:NSO2Ph and (Me2CHCH2CH2O)2P(O)H in Et2O gave 85% title compd. (Me2CHCH2CH2O)2P(O)C(CF3)2NHSO2Ph, the structure of which was detd. by x-ray crystallog.

Assessment of the neurotoxic potential of some methyl- and phenylphosphonates using a stable preparation of neuropathy target esterase from chicken brain. Makhaeva G F; Malygin V V; Martynov I V Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Moscow Oblast, 142432 Russia Doklady. Biochemistry and biophysics (2001 Mar-Apr), 377 68-71.

megalomania
April 15th, 2005, 05:49 PM
It has occured to me that a little social networking is in order to track down all possible scientific articles about Novichok agents and chemical weapons in general. Thanks to the papers provided by Samosa and Fritz I have used the names of the authors in those articles as a basis for a search for all of their respective articles.

The theory is whoever publishes an article about a chemical weapon has probably published other articles on chemical weapons. The theory also stipulates whoever he co-authored these papers with also probably work in chemical weapons, so their articles are likely to be related to chemical weapons research.

The end result is I have nearly 1000 articles published by the top dozen names, leading me to dozens more authors. I now have to sift through the first batch of all the articles to weed out any unrelated publications, and to find out who the co-authors of the good articles are.

I also read a tidbit in Tobiasons Scientific Principles, the chemical weapons volume, that the Soviets intentionally published large amounts of chemical weapons information in the open literature in the 1950s and 1960s with the hope some rogue nation would use the information to attack the US. The goal here was for the rogue state to finish the job for the Soviet Union, or at least inflict massive American casualities. Now all I need to do is find out what journals they published this stuff in. Zhurnal Obshchei Khimii is probably a good place to start since it has an English translation.

Also, in the paper by Mr Samosa the molecular structures for the two examples of Novichok compounds are incorrect. I donít know if the CAS numbers are wrong for the right structures, or if the structures are wrong for the right CAS number. I think the wrong structures were used for the right CAS numbers.
(see attached image)

One name that seems to pop up a lot is I. V. Martynov. He has published about 500 journal articles in his lifetime to date. Indeed there are many about phosphorus compounds, but those type of articles cease after 1972. He publishes many articles about molecular refraction after that. In 1984 he resumes publication of phosphorus related articles.

One article in particular caught my eye:
Synthesis and anticholinesterase activity of fluorochloronitroacetic acid esters. Ivanov, Yu. Ya.; Brel, V. K.; Postnova; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1985), 19(8), 968-71.

There are a few earlier articles about fluorochloronitroacetic acid esters. These are important in the systhesis of Novichoks I would imagine. Samosa did mention in his paper (NovDAGVGP.doc attached earlier) that dihaloformaldoxime are critical parts of Novichok agents, and fluorochloronitroacetic acid should form those.

Another article Martynov published related to bicyclic phosphates. There is another thread Samosa started about those. I donít know enough about them to say if this article is of interest. The abstract mentions this compound is a chloride blocker, it blocks GABA-independent Cl- channels specificially. Perhaps someone with knowledge of biology can say if blocking those is lethal. The article is:
4-Methyl- and 4-ethylbicyclophosphates, blockers of chloride channels. Fetisov, V. I.; Redkozubov, A. E.; Lyubimov, V. S.; Sokolov, V. S.; Martynov, I. V.. USSR. Biologicheskie Membrany (1986), 3(9), 968-70.
4-Methyl- (I; R = Me) [1449-89-4] and 4-ethylbicyclophosphate (I; R = Et) [1005-93-2] were effective blockers of GABA-independent Cl- channels (of Limnaea stagnalis giant neurons). Both potential and thermoregulation of the Cl- channels were affected.


Here is another article of potential use in the preparation of Novichok agents. This compound is similar to fluorochloronitroacetic acid from which this substance is made:
Synthesis of chlorofluoronitronitrosomethane. Martynov, I. V.; Brel, V. K.; Uvarova, L. V. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1986), (4), 952-3.
Decarboxylation-nitrosation of ClFC(NO2)CO2H with HNO3 gave 52% ClFC(NO)NO2

Here is another possible tidbit as it relates to insecticides and plant growth regulation. We know they disguised their research under the guise of agrichemicals:
Synthesis and pesticidal activity of chloronitroacetic acid esters. Martynov, I. V.; Yurtanov, A. I.; Ivanov, Yu. J.; Kulish, E. V.; Uvarova, L. V.; Andreeva, E. I.; Rozhkova, N. G.; Zhirmunskaya, N. M. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1986), 289(1), 109-13 [Chem.].
A series of 31 O2NCRR1CO2R [e.g., R, R1, R2 = H, Cl, n-C7H15 (I); F, Cl, ClCH2CH2; Br, Cl, Et] was tested for insecticidal and, in some cases, plant growth regulatory activity. Eight of the compds., e.g., I, were active insecticides. Twelve of the compds. were new but no prepn. details were given.

Here is another possible Novichok variant:
Reaction of phosphorus trichloride with 1,1,2-trichloro-1-nitrosoethane in sulfur dioxide. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1986), (9), 2158.
Reaction of ClCH2CCl2NO with PCl3 in SO2 gave 58% ClCH2CCl:NOP(O)Cl2.


Here is yet another possible Novichok variant:
Reaction of dialkyl phosphites with 1,1-dichloronitrosoalkanes. Ivanov, A. N.; Epishina, T. A.; Goreva, T. V.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (1), 226-8.
(RO)2P(O)ON:CClR1 (R = Bu, Me2CHCH2, pentyl, Me, Et; R1 = Me, Et, Pr, Me2CH, Bu, Me2CHCH2) were prepd. in 44-67% yields by treating (RO)2POH with ONCCl2R1 in EtOH at 20.

Here is a toxicity study done on animals and humans for some pesticides. Yeah, pesticides, thatís the ticket:
Delayed neurotoxicity from organophosphorus pesticides. Makhaeva, G. F.; Malygin, V. V.; Martynov, I. V.. USSR. Agrokhimiya (1987), (12), 103-24.
A review with 123 refs. on 8 clin. intoxication symptoms, pathmorphol., mechanisms of initiation of delayed neurotoxicity by organophosphorus pesticides (OPP) structure-activity relations of OPP, monitoring of the delayed neurotoxicity of OPP in animals and humans, etc.

Here is another possible Novichok variant:
Reaction of O-alkyl methylphosphonites with 1,1-dichloro-1-nitrosopropane. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(4), 952-3.
Reaction of ROP(O)HMe (R = Me2CH, Bu, pentyl) with EtCCl2NO in Et2O gave 50-52% ROP(O)MeON:CClEt (I; same R). Treating MeP(OR)2 with EtCCl2NO also gave I.

Here is an interesting reference, although I doubt this would have very high human toxicity due to the two large aryl groups attached to phosphorus. Still, it gives enlightenment as to where they are headed:
Reaction of diphenylphosphinous acid with 1,1-dichloro-1-nitrosoalkanes. Sokolov, V. B.; Epishina, T. A.; Ivanov, A. N.; Kharitonov, A. V.; Brel, V. K.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(7), 1658-9.
Treating Ph2P(O)H with RCCl2NO (R = Et, Pr, Me2CH) in Et2O gave 62-75% Ph2P(O)ON:CClR (same R).


Another Novichok possibility:
Synthesis and the structure of dialkylfluoroformiminophosphates. Martynov, I. V.; Brel, V. K.; Uvarov, V. I.; Yarkov, A. V.; Novikov, V. P.; Chepakova, L. A.; Raevskii, O. A. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (4), 857-60.
Syn- And anti-(RO)2P(O)N:CHF (R = Me, Et, Pr, Bu) were prepd. in 11-25% yields by treating (RO)3P with ClCHFNO2.

Here is some nasty looking stuff that may be of interest:
Reaction of (-aminoalkyl)phosphonates with perfluoro-2-azapropene. Aksinenko, A. Yu.; Pushin, A. N.; Sokolov, V. B.; Gontar, A. F.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (5), 1177-9.
(RO)2P(O)CMeR1N:C:NCF3 (R = Me, R1 = Et; R = Et, R1 = Et, Pr, Bu; R = Me2CHCH2, R1 = Et) were prepd. in 40-60% yields by condensing CF2:NCF3 with (RO)2P(O)CMeR1(NH2) in the presence of KF.

Here is another variant:
Reaction of polychloronitrosoethanes with phosphorous acid derivatives. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (5), 1086-9.
The title reaction gave 20-93% of 22 o-phosphorylated alkyl chloroformimines. Thus, treating ONCCl2R (R = Me, CH2Cl, CHCl2) with (R1O)3P (R1 = Me, Pr, Bu, Me2CHCH2, pentyl, ClCH2CH2) gave (R1O)2P(O)ON:CClR.

Of all the other compounds I have previously referenced this particular compound looks like it may be the deadliest. It has some similarities to most other nerve gasses in that it uses the simplest alkyl groups, and has a direct alkyl and a direct halogen attachment to phosphorus. I would replace those chlorines with fluorine to increase the toxicity:
Reaction of dichloromethylphosphine with 1,1-dichloro-1-nitrosoalkanes. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(7), 1659-60.
MePCl2 reacted with RCCl2NO (R = Et, Pr, Me2CH) in SO2 to give 27-37% RCCl:NOP(O)ClMe.

This compound looks like a good precursor for organophosphorus agents like the previous compound. The chlorines can be replaced by F, and one of the fluorines can form an ester or something else. The second compound is an example of what could be made, and I just bet that stuff is pretty toxic.
Interaction of 2,2,3,3-tetrafluoropropyl dichlorophosphite with 1,1,2-trichloro-1-nitrosoethane. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (6), 1422-3.
Refluxing CHF2CF2CH2OPCl2 (I) with CH2ClCCl2NO (II) in Et2O gave 67.8% Cl2P(O)ON:CClCH2Cl. Treating I with II in SO2 at 20 gave 48.2% (CHF2CF2CH2O)ClP(O)ON:CClCH2Cl.

We might have a real winner with this one as it has similarities with VX nerve gas. The second compound in particular has a =S group. If that could be isomerized, like it is done in making VX, then we have a thioester. The two isobutyl groups are probably too large to make this particular compound all that toxic. I am sure they could be replaced with methyls instead.
Reaction of diisobutylchlorophosphine with 1,1-dichloro-1-nitrosoalkanes in presence of sulfur dioxide and ethyl mercaptan. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (11), 2586-8.
Treating (Me2CHCH2)2PCl with RCCl2NO (R = Me, Et, Pr, Me2CH) in Et2O contg. SO2 gave 61-74% (Me2CHCH2)2P(O)ON:CRCl (same R). When Et2SH was used instead of SO2, 44% (Me2CHCH2)2P(S)ON:CRCl (R = Me) was obtained.

Another phenyl attached compound:
Synthesis and molecular structure of (O-isopropylchloroformimino) diphenylphosphinate. Martynov, I. V.; Chekhlov, A. N.; Ivanov, A. N.; Epishina, T. A.; Makhaev, V. D.; Sokolov, V. B. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (11), 2595-7.
Treating Ph2PH with Me2CHCCl2NO in C6H6 gave 58% Ph2P(O)ON:CClCHMe2, the structure of which was detd. by x-ray crystallog.

This compound has some VX similarities too:
O,O-Dialkyl O-(dialkylformimino) thiophosphates. Chepakova, L. A.; Brel, V. K.; Pushin, A. N.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(12), 2716-19.
Twelve (R1O)2P(S)ON:CMeR (R = Me, Et, Pr; R1 = Me, Et, Pr, Bu) were prepd. in 41-62% yields by treating (R1O)2PHS with ONCClMeR or HON:CMeR.

These compounds are similar to the last journal reference except the R and Rí groups are switched. Isomerize that S and we may have something far more toxic.
O-(Alkylchloroformimino) O,O-dialkyl thiophosphates. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (12), 2854-5.
Seven (RO)2P(S)ON:CClR1 (R = Et, Me2CH; R1 = Me, Et, Pr, Me2CH, ClCH2) were prepd. in 33-54% yields by condensing (RO)2PSH with R1Cl2CNO in THF.

Martynov has 64 publications in 1988 alone, his best year. In no particular order here are some highlights:

Molecular and crystal structure of O,O-diethyl 1-[N2-(trifluoromethyl)fluoroformamidino]-1-methylethylphosphonate. Chekhlov, A. N.; Aksinenko, A. Yu.; Sokolov, V. B.; Korenchenko, O. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1988), 302(4), 855-8 [Chem.].
The crystal and mol. structure of (EtO)2P(O)CMe2NHCFNCF3 was detd.

Reaction of (N-acetyl-N-ethylamido)alkylphosphonic acid chlorides with cesium fluoride. Krolevets, A. A.; Adamov, A. V.; Popov, A. G.; Martynov, I. V.. USSR. Zhurnal Obshchei Khimii (1988), 58(11), 2628-9.
RP(O)F(NEtCH:CH2) (R = Me, Me2CH) were prepd. in 45, 50% yields, resp., by treating RPCl(NEtAc) (I) with CsF. I were prepd. in 60, 65% yields, resp., by treating RPCl2 with Me3SiNEtAc.

Stable alkoxyfluorophosphoranes. Krolevets, A. A.; Popov, A. G.; Adamov, A. V.; Martynov, I. V.. USSR. Zhurnal Obshchei Khimii (1988), 58(11), 2626-7.
RPF2(OR1)2 (R = BuCHClCH2, R1 = Me3C; R = Me2CClCH2, R1 = Et) were prepd. in 45, 40% yields, resp., by treating RPF4 with Me3SiOR1.

O-(Alkylchloroformimidoyl) o-alkyl methylphosphonates. Sokolov, V. B.; Ivanov, A. N.; Goreva, T. V.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (5), 1128-30.
Nine (RO)MeP(O)ON:CClR1 (R = Et, Pr, Bu, Me2CH, pentyl; R1 = Me, Et, Pr, Bu, Me2CH) were prepd. in 41-67% yields by treating R1CCl2NO with MeP(OR)2 or MeP(O)H(OR).

Reaction of 1,1-dichloro-1-nitrosoalkanes with phosphorus(III) chlorides. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (9), 2128-32.
The title reaction was studied. Thus, R1R2P(O)ON:CRCl (R = Me, Et, Pr, Me2CH; R1 = R2 = Cl, Me2CHCH2; R1 = Cl, R2 = Me) were prepd. in 34-74% yields by reaction of RCCl2NO with R1R2PCl in the presence of SO2.

Synthesis and x-ray diffraction study of N-(diisopropoxythiophosphoryl)thioacetamide. Solov'ev, V. N.; Chekhlov, A. N.; Zabirov, N. G.; Cherkasov, R. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1988), 300(6), 1386-9 [Chem.].
Treating MeCSNH2 with Me3COK in MeCN and then with ClP(S)(OCHMe2)2 gave 15% MeCSNHP(S)(OCHMe2)2, the structure of which was detd. by x-ray crystallog.

Reaction of 1,1-dichloro-1-nitrosoethane with phosphorus oxychloride in the presence of zinc. Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (7), 1691.
Cl2P(O)ON:CClMe was prepd. in 26.6% yield by treating MeCCl2NO with POCl3 in the presence of Zn.

Comparative studies on the interaction of acetylcholinesterases from human erythrocytes and housefly heads with phosphorylated alkylchloroformoxims. Shataeva, G. A.; Makhaeva, G. F.; Yankovskaya, V. L.; Sokolov, V. B.; Ivanov, A. N.; Martynov, I. V.. Inst. Physiol. Act. Subst., Chernogolovka, USSR. Zhurnal Evolyutsionnoi Biokhimii i Fiziologii (1988), 24(6), 791-6.
Among Valexon analogs, 6 (RO)2P(O)ON:CClMe (I), 6 (RO)2P(O)ON:C(Cl)CH2Cl (II), and 5 (RO)2P(O)ON:C(Cl)CHCl2 (III, R = Me, Et, Pr, iso-Bu, Bu, amyl), and 4 (EtO)2P(O)ON:C(Cl)R1 (IV, R1 = Me, Et, Pr, Bu), I-III (R = Et) were highly selective insecticides, having rate consts. of bimol. reaction with acetylcholinesterase (KII) of human erythrocytes (HE) lower by 1 magnitude order than with that from housefly heads (FL). Inhibition of both HE and FL followed the order I < II < III. Phosphorylation capacity of II 1.6-fold exceeded that of I. Replacing Me by Et, increased the effect of I-III on FL 3-8-fold and decreased that on HE 1.7-4-fold. Further increases in hydrophobicity abolished the specificity of I-III. The selectivity of IV decreased in order of R1: Me > Et > Bu; IV (R1 = Pr) showed no selectivity.

Fluorination of some phosphoric acid derivatives. Zavorin, S. I.; Lermontov, S. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka., USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (5), 1174-6.
Dialkyl fluorophosphates were prepd. by the title fluorination with Et3N.3HF (I). Thus, fluorination of (EtO)2P(O)ON:CCl2 with I in MeCN gave 83.5% (EtO)2P(O)F.

Reaction of fluorine-containing acetylenic alcohols with phosphorus trichloride. Brel, V. K.; Chekhlov, A. N.; Ionin, B. I.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1988), 58(4), 750-7.
Treating RC.tplbond.CCMe(OH)CH2F (I; R = Ph) with PCl3 in Et2O gave 45% Cl2P(O)CR:C:CMeCH2F (II; R = Ph) and 24% E- and Z-Cl2P(O)CHPhCCl:CMeCH2F (III). Under the same conditions, I (R = MeOCH2) gave a mixt. of II (R = MeOCH2) and Cl2P(O)C(:CH2)CCl:CMeCH2F. Treating I (R = Ph) with MeOH and then with Br2 gave oxaphospholene IV. The structure of III was detd. by x-ray crystallog.

Synthesis and anticholinesterase activity of fluorochloronitroacetic acid thioesters. Ivanov, Yu. Ya.; Uvarov, V. I.; Brel, V. K.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1988), 22(5), 538-40.
Treating O2NCFClCOX (I; X = OH) with PCl5 gave I (X = Cl), which reacted with RSH (R = Et, Bu) to give 35-55% I (X = SR; same R) (II). II were less effective acetylcholinesterase inhibitors than I (X = OR; same R) but had comparable activity vs. butyrylcholinesterase with lower toxicity.

Synthesis and antiesterase activity of sulfur-containing phosphorylated oximes. Chepakova, L. A.; Bret, V. K.; Makheva, G. F.; Yankovskaya, V. L.; Beznosko, B. K.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1988), 22(2), 143-6.
Reaction of (RS)2POEt (R = Et, Pr, iso-Bu, Bu or amyl) with O:NCFCl2 gave the corresponding (RS)2P(:O)ON:CClF (I). An increase in the hydrophobicity of I did not alter the anticholinesterase activity of I, while the butyrylcholinesterase and carboxylesterase activity were increased.

O-substituted alkylchloroformoximes as substrates and inhibitors of cholinesterases. Ivanov Iu Ia; Sokolov V B; Epishina T A; Martynov I V Doklady Akademii nauk SSSR (1990), 310(5), 1253-5.

Inhibition of cholinesterase activity with fluorine-containing derivatives of alpha-aminophosphonic acid. Kuusk V V; Morozova I V; Agabekian R S; Aksinenko A Iu; Epishina T A; Sokolov V B; Kovaleva N V; Razdol'skiy A N; Fetisov V N; Martynov I V Bioorganicheskaia khimiia (1990 Nov), 16(11), 1500-8.
A series of O,O-diethyl-1-(N-alpha-hydrohexafluoroisobutyryl)aminoalkylphos phonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate constants and the enzyme-inhibitor intermediate dissociation constants are calculated. The quantitative structure-activity relationships including both hydrophobic and calculated steric parameters of substituents are developed for APh--ChE interactions. Molecular mechanics (programme MM2) was used for determining steric parameters (Es). On the basis of QSAR models analysis it was concluded that hydrophobic interactions play an essential role in APh--AChE binding, whereas for APh--BuChE binding steric interactions are essential. Presence of at least two APh binding centres on the surface of AChE and BuChE is suggested.

Reaction of 1,1-dichloro-1-nitrosobutane with (N,N-dimethylamido)dichlorophosphite. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (6), 1416-18.
Reaction of PrCCl2NO with Me2NPCl2 in Et2O or in SO2 gave 36% Me2NPCl4 or 30% Me2NP(O)ClON:CClPr, resp. Treating Me2NPCl4 with SO2 gave 91% Me2NP(O)Cl2. Reaction of PrCCl2NO with Me2NPCl2 in Et2O, and then with Ph3P and distn. gave Ph3PO and PrCN.

Alkyl chlorofluoroformimino perfluoroalkylphosphonates. Chepakova, L. A.; Brel, V. K.; Martynov, I. V.; Maslennikov, I. G. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Zhurnal Obshchei Khimii (1989), 59(6), 1455-6.
Treating RP(OR1)2 (R = CF3, R1 = Pr, Bu; R = CF3CF2, R1 = Me, Bu) with CFCl2NO in Et2O gave 76-88% title compds. R1OP(O)RON:CFCl.

Synthesis of dialkyl (3-alkyl-1,3-alkadien-2-yl)phosphonates. Brel, V. K.; Abramkin, E. V.; Martynov, I. V.; Ionin, B. I. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1989), 59(9), 2142-3.
(RO)2P(O)C(:CH2)CR1:CMe2 (R = Et, Pr; R1 = Me, Et) were prepd. in 41-73% yields by the Grignard reaction of (RO)2P(O)C(CH2OMe):C:CMe2 with R1X (X = halo).

Synthesis and antiesterase activity of O,O-dialkyl S-(ethoxycarboxyl)chloromethyl thiophosphates. Khaskin, B. A.; Makhaeva, G. F.; Torgasheva, N. A.; Ishmuratov, A. S.; Yankovskaya, V. L.; Fetisov, V. I.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovko, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (12), 2741-6.
The title compds. (RO)2P(O)SCHClCO2Et (I; R = alkyl homologs) were prepd. in 82-95% yields in the reaction of (RO)2P(O)SCl with N2CHCO2Et at -25 (in Et2O) or 6-7 (in benzene), presumably via a noncarbene mechanism. I irreversibly inhibited acetylcholinesterase, butyrylcholinesterase, and carboxylesterase; antibutyrylcholinesterase activity increased in the homologous series of R, with max. at R = Bu. An antiesterase MSBAR of I was fulfilled with parameters representing hydrophobicity and steric properties of R.

Synthesis and cholinesterase hydrolysis of O-acylated alkylchloroformoximes. Sokolov, V. B.; Ivanov, Yu. Ya.; Epishina, T. A.; Agabekyan, R. S.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1989), 23(11), 1317-20.
The title compds., RCO2N:CClR1 (R = Me, Et, Pr or CH2Cl and R1 = Me, Et, Pr, or iso-Pr) were prepd. e.g., by the reaction of 1,1-dichloro-1-nitrosobutane with AcCl in the presence of Zn. These compds. were good substrates for acetyl- and butyrylcholinesterases. The kinetic parameters (Km, Vmax and ac) of these compds. in the hydrolysis reactions were comparable to those with acetylcholine. The acute toxicity was 79-381 mg/kg in mice given drugs orally.

Synthesis and structure of O,O-dialkyl 2-[(ethoxycarbonyl)amino]hexafluoroisopropylphosphonates. Aksinenko, A. Yu.; Chekhlov, A. N.; Korenchenko, O. V.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1990), 60(1), 61-5.
The title compds. (RO)2P(O)C(CF3)2NHCO2Et (I; R = Me, Et, CHMe2) were prepd. in 54-76% yields in the reaction of (RO)2P(O)H with (CF3)2C:NCO2Et. The crystal and mol. structure of I (R = Et) was detd.

O-Substituted alkylchloroformoximes as substrates and inhibitors of cholinesterases. Ivanov, Yu. Ya.; Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1990), 310(5), 1253-5 [Biochem.].
The ability of O-substituted alkylchloroformoximes to serve as substrates for acetylcholinesterase (ACE, EC 3.1.1.7) and butyrylcholinesterase (BCE, EC 3.1.1.8) and to inhibit acetylcholine hydrolysis by these enzymes was detd., along with the LD50 of these compds. in mice. The compds. tested were O-acylated alkylchloroformoximes of the general formula R1C(O)ON:C(Cl)R2 [R1 = R2 = Me; R1 = Me, R2 = Et; R1 = Me, R2 = Pr; R1 = Et, R2 = Me; R1 = Et, R2 = iso-Pr; R1 = Pr, R2 = iso-Pr; R1 = CH2Cl, R2 = Pr (I); R1 = CH2Cl, R2 = iso-Pr (II)], O-carbonylated alkylchloroformoximes of the general formula EtOC(O)ON:C(Cl)R [R = Me (III), iso-Pr (IV)], and O-carbamoylated alkylchloroformoximes of the general formula (Me)2NC(O)ON:C(Cl)R [R = Me (V), iso-Pr (VI)]. All of the compds. except for I and II were good substrates for the enzymes, with Km values for ACE ranging (0.3-11.0)  10-4M and for BCE ranging (0.5-13.0)  10-4M (the Km values of ACE and BCE with acetylcholine were 1.3  10-4 and 5.4  10-4M, resp.). III and IV were competitive (Ki 1.6  10-4M) and mixed-type (Ki 4.2  10-4M) inhibitors, resp., of ACE. V and VI were effective inhibitors of both ACE and BCE, with bimol. rate consts. for inhibition (kII) of 5.7  103 and 1.4  105 M-1 min-1, resp., for ACE, and 9.8  103 and 5.4  106 M-1 min-1, resp., for BCE. The LD50 values for the tested compds. ranged 60-381 mg/kg body wt.

O-(alkylchloroformimino)(methyl)thiophosphonic acid chlorides. Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (12), 2865-6.
Treating the adduct from RCCl2NO and MePCl2 with H2S gave 21-35% MeP(S)ClON:CRCl.

Interaction of 1,1-dichloro-1-nitrosoalkanes with S-ethylmethylphosphonous chloride in the presence of sulfur dioxide. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1990), (2), 464-5.
EtSP(O)MeON:CClR (R = Me, Et, Pr) were prepd. in 42-47% yields by treating RCCl2NO with EtSPMeCl in the presence of SO2.

O-(alkylchloroformimino)-O-alkylphosphoric acid chlorides. Sokolov, V. B.; Ivanov, A. N.; Goreva, T. V.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1990), (5), 1122-5.
Reaction of (ON)CCl2R with (R'O)2PCl (R, R' = alkyl) afforded the title compds. (R'O)ClP(O)ON:CRCl (I) in up to 69% yield. Hydrolysis of I led to substitution of P-, and not C-bound Cl, resulting in (R'O)(NH4O)P(O)ON:CRCl.

Reaction of the adduct of methyldichlorophosphine and 1,1-dichloro-1-nitrosoethane with thioacetic acid. Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1990), 60(8), 1923-4.
Treating MePCl2 with MeCCl2NO in PhMe, followed by addn of 1 or 2 equiv AcSH gave 56% MeP(S)ClON:CMeCl or 32% MeP(S)ClON:CMeSAc, resp.

Inhibition of cholinesterase activity by fluorine-containing derivatives of -aminoalkylphosphonic acids. Kuusk, V. V.; Morozova, I. V.; Agabekyan, R. S.; Aksinenko, A. Yu.; Epishina, T. A.; Sokolov, V. B.; Kovaleva, N. V.; Razdol'skii, A. N.; Fetisov, V. I.; Martynov, I. V.. Inst. Physiol. Act. Subst., Chernogolovka, USSR. Bioorganicheskaya Khimiya (1990), 16(11), 1500-8.
A series of O,O-diethyl-1-(N--hydrohexafluoroisobutyryl)aminoalkylphosphonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate consts. and the enzyme-inhibitor intermediate dissocn. consts. are calcd. The quant. structure-activity relationships including both hydrophobic and calcd. steric parameters of substituents are developed for APh-ChE interactions. Mol. mechanics (program MM2) was used for detg. steric parameters (Es). On the basis of QSAR models anal. it was concluded that hydrophobic interactions play an essential role in APh-AChE binding, whereas for APh-BuChE binding steric interactions are essential. Presence of at least two APh binding centers on the surface of AChE and BuChE is suggested.

Synthesis and anticholinesterase activity of O-carbamoylated alkylchloroform oximes. Sokolov, V. B.; Ivanov, Yu. Ya.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshestva, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1991), 25(4), 33-4.
Treating ClCO2N:CClR (R = Me, Et, Pr, CHMe2) with NHR1R2 (R1 = R2 = H, Me, Et; R1 = H, R2 = Me) in Et2O gave 50-69% R1R2NCO2N:CClR (same R-R3), which are acetyl- and butyrylcholinesterase inhibitors (k11 = 1.1  10-2 to 5.4  10-6 M-1 min-1). Acute oral toxicity in mice ranged from 32 to 565 mg/kg.

O-Alkyl O-methylchloroformimino phenylphosphonates - effective inhibitors of the hen brain neurotoxic esterase. Makhaeva, G. F.; Kononova, I. V.; Malygin, V. V.; Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1991), 317(4), 1009-12 [Biochem.].
The title phosphonates were effective inhibitors of neurotoxic esterase; with increasing hydrophobicity the compds. showed pronounced and selective biol. activity towards brain neurotoxic esterase compared to acetylcholinesterase. Thus, the structure of phenylphosphonate played a major role in the inhibitory effects of these potential pesticides towards neurotoxic esterase or acetylcholinesterase.

Synthesis and anticholinesterase activity of fluorine-containing -aminophosphoryl compounds. Korenchenko, O. V.; Ivanov, Yu. Ya.; Aksinenko, A. Yu.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Khimiko-Farmatsevticheskii Zhurnal (1992), 26(6), 21-3.
Reaction of R2P(O)H (R = MeO, EtO, PrO, Me2CHO, Ph) with (CF3)2C:NCOR1 (R1 = OEt, OCH2Ph, OPr, OBu, OCH2CH2CHMe2, CF3) in Et2O gave 44-93% R2P(O)C(CF3)2NHCOR1. Treating a 1,4,2-oxazaphospholine deriv. with alcs. gave Me(R)P(O)C(CF3)2NHCO2Et (R = BuO, Me2CHO). Bimol. rate consts. for inhibition of cholinesterases by these compds. were detd.

Synthesis and insecticidal and acaricidal activity of O-alkylchloroformimine O,O-dialkyl phosphates and O,O-dialkylthiophosphates. Ivanov, A. M.; Ivanova, G. B.; Sokolova, V. B.; Epishina, T. N.; Goreva, T. V.; Beznosko, B. K.; Martynov, I. V.. Inst. Fiziol. Okl. Veshchestv., Chernogolovka, Russia. Fiziologicheski Aktivnye Veshchestva (1991), 23 58-62.
Of 26 title compds., those having ethoxy group at P were both insecticides and acaricides, whereas those having their methoxy group showed insecticidal activity only. Increasing hydrophobicity of the alkoxy substituents decreased i.m. toxicity to mice, but also the effectiveness. O replacement by S also decreased toxicity. Synthesis is indicated.

Paradoxical toxic effect and calcium antagonism of the cholinesterase inhibitors O-(N-arylcarbamoyl)acylhydroximoyl chlorides. Ivanov, Yu. Ya.; Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Doklady Akademii Nauk (1993), 328(6), 744-6 [Biochem.].
N-phenylcarbamates and aliph. analogs of the formula R R1N(O)ON::C(Cl)R2 [where R = Et, Me, and Ph; R1 = H, Me; R2 = Et, Pr, iso-Pr] were examd. for their acetylcholinesterase and butyrylcholinesterase inhibition, for their acute toxicity and their action on selective organs. The enzyme inhibition depended on their mol. structure. Paradoxical effects (higher dose and low toxicity and vice versa) were noted.

Similar sensitivity of rat and hen brain neurotoxic esterase to inhibition by O-alkyl-O-alkylchloroformiminophenylphosphonates. Makhaeva, G. F.; Filonenko, I. V.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Doklady Akademii Nauk (1993), 332(5), 650-3.
Quant. structure-neurotoxic esterase (NTE)-inhibiting activity relationship of the title phosphonates was examd. against both rat and chicken enzyme. The phosphonates effectively inhibited the enzyme from both the sources. The anti-NTE activity of the compds. increased with the length of alkyl radical in the phosphoryl portion. The introduction of branched substituent, esp. in the -position, decreased the antienzyme activity. Math. equations are derived to describe the effects of steric factors on the NTE inhibition. PI50 = -lg I50, where I50 is the concn. of the inhibitor required to cause 50% inhibition, was calcd. for these compds.; the values are tabulated.

Crystal and molecular structures and synthesis of O,O-diisopentyl 1-(phenylsulfonamido)-1-(trifluoromethyl)-2,2,2-trifluoroethylphosphonate. Chekhlov, A. N.; Aksinenko, A. Yu.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Ross. Akad. Nauk, Chernogolovka, Russia. Doklady Akademii Nauk (1995), 345(3), 360-363.
Reaction of (CF3)2C:NSO2Ph and (Me2CHCH2CH2O)2P(O)H in Et2O gave 85% title compd. (Me2CHCH2CH2O)2P(O)C(CF3)2NHSO2Ph, the structure of which was detd. by x-ray crystallog.

Assessment of the neurotoxic potential of some methyl- and phenylphosphonates using a stable preparation of neuropathy target esterase from chicken brain. Makhaeva G F; Malygin V V; Martynov I V Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Moscow Oblast, 142432 Russia Doklady. Biochemistry and biophysics (2001 Mar-Apr), 377 68-71.

megalomania
April 15th, 2005, 05:49 PM
It has occured to me that a little social networking is in order to track down all possible scientific articles about Novichok agents and chemical weapons in general. Thanks to the papers provided by Samosa and Fritz I have used the names of the authors in those articles as a basis for a search for all of their respective articles.

The theory is whoever publishes an article about a chemical weapon has probably published other articles on chemical weapons. The theory also stipulates whoever he co-authored these papers with also probably work in chemical weapons, so their articles are likely to be related to chemical weapons research.

The end result is I have nearly 1000 articles published by the top dozen names, leading me to dozens more authors. I now have to sift through the first batch of all the articles to weed out any unrelated publications, and to find out who the co-authors of the good articles are.

I also read a tidbit in Tobiasons Scientific Principles, the chemical weapons volume, that the Soviets intentionally published large amounts of chemical weapons information in the open literature in the 1950s and 1960s with the hope some rogue nation would use the information to attack the US. The goal here was for the rogue state to finish the job for the Soviet Union, or at least inflict massive American casualities. Now all I need to do is find out what journals they published this stuff in. Zhurnal Obshchei Khimii is probably a good place to start since it has an English translation.

Also, in the paper by Mr Samosa the molecular structures for the two examples of Novichok compounds are incorrect. I donít know if the CAS numbers are wrong for the right structures, or if the structures are wrong for the right CAS number. I think the wrong structures were used for the right CAS numbers.
(see attached image)

One name that seems to pop up a lot is I. V. Martynov. He has published about 500 journal articles in his lifetime to date. Indeed there are many about phosphorus compounds, but those type of articles cease after 1972. He publishes many articles about molecular refraction after that. In 1984 he resumes publication of phosphorus related articles.

One article in particular caught my eye:
Synthesis and anticholinesterase activity of fluorochloronitroacetic acid esters. Ivanov, Yu. Ya.; Brel, V. K.; Postnova; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1985), 19(8), 968-71.

There are a few earlier articles about fluorochloronitroacetic acid esters. These are important in the systhesis of Novichoks I would imagine. Samosa did mention in his paper (NovDAGVGP.doc attached earlier) that dihaloformaldoxime are critical parts of Novichok agents, and fluorochloronitroacetic acid should form those.

Another article Martynov published related to bicyclic phosphates. There is another thread Samosa started about those. I donít know enough about them to say if this article is of interest. The abstract mentions this compound is a chloride blocker, it blocks GABA-independent Cl- channels specificially. Perhaps someone with knowledge of biology can say if blocking those is lethal. The article is:
4-Methyl- and 4-ethylbicyclophosphates, blockers of chloride channels. Fetisov, V. I.; Redkozubov, A. E.; Lyubimov, V. S.; Sokolov, V. S.; Martynov, I. V.. USSR. Biologicheskie Membrany (1986), 3(9), 968-70.
4-Methyl- (I; R = Me) [1449-89-4] and 4-ethylbicyclophosphate (I; R = Et) [1005-93-2] were effective blockers of GABA-independent Cl- channels (of Limnaea stagnalis giant neurons). Both potential and thermoregulation of the Cl- channels were affected.


Here is another article of potential use in the preparation of Novichok agents. This compound is similar to fluorochloronitroacetic acid from which this substance is made:
Synthesis of chlorofluoronitronitrosomethane. Martynov, I. V.; Brel, V. K.; Uvarova, L. V. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1986), (4), 952-3.
Decarboxylation-nitrosation of ClFC(NO2)CO2H with HNO3 gave 52% ClFC(NO)NO2

Here is another possible tidbit as it relates to insecticides and plant growth regulation. We know they disguised their research under the guise of agrichemicals:
Synthesis and pesticidal activity of chloronitroacetic acid esters. Martynov, I. V.; Yurtanov, A. I.; Ivanov, Yu. J.; Kulish, E. V.; Uvarova, L. V.; Andreeva, E. I.; Rozhkova, N. G.; Zhirmunskaya, N. M. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1986), 289(1), 109-13 [Chem.].
A series of 31 O2NCRR1CO2R [e.g., R, R1, R2 = H, Cl, n-C7H15 (I); F, Cl, ClCH2CH2; Br, Cl, Et] was tested for insecticidal and, in some cases, plant growth regulatory activity. Eight of the compds., e.g., I, were active insecticides. Twelve of the compds. were new but no prepn. details were given.

Here is another possible Novichok variant:
Reaction of phosphorus trichloride with 1,1,2-trichloro-1-nitrosoethane in sulfur dioxide. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1986), (9), 2158.
Reaction of ClCH2CCl2NO with PCl3 in SO2 gave 58% ClCH2CCl:NOP(O)Cl2.


Here is yet another possible Novichok variant:
Reaction of dialkyl phosphites with 1,1-dichloronitrosoalkanes. Ivanov, A. N.; Epishina, T. A.; Goreva, T. V.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (1), 226-8.
(RO)2P(O)ON:CClR1 (R = Bu, Me2CHCH2, pentyl, Me, Et; R1 = Me, Et, Pr, Me2CH, Bu, Me2CHCH2) were prepd. in 44-67% yields by treating (RO)2POH with ONCCl2R1 in EtOH at 20.

Here is a toxicity study done on animals and humans for some pesticides. Yeah, pesticides, thatís the ticket:
Delayed neurotoxicity from organophosphorus pesticides. Makhaeva, G. F.; Malygin, V. V.; Martynov, I. V.. USSR. Agrokhimiya (1987), (12), 103-24.
A review with 123 refs. on 8 clin. intoxication symptoms, pathmorphol., mechanisms of initiation of delayed neurotoxicity by organophosphorus pesticides (OPP) structure-activity relations of OPP, monitoring of the delayed neurotoxicity of OPP in animals and humans, etc.

Here is another possible Novichok variant:
Reaction of O-alkyl methylphosphonites with 1,1-dichloro-1-nitrosopropane. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(4), 952-3.
Reaction of ROP(O)HMe (R = Me2CH, Bu, pentyl) with EtCCl2NO in Et2O gave 50-52% ROP(O)MeON:CClEt (I; same R). Treating MeP(OR)2 with EtCCl2NO also gave I.

Here is an interesting reference, although I doubt this would have very high human toxicity due to the two large aryl groups attached to phosphorus. Still, it gives enlightenment as to where they are headed:
Reaction of diphenylphosphinous acid with 1,1-dichloro-1-nitrosoalkanes. Sokolov, V. B.; Epishina, T. A.; Ivanov, A. N.; Kharitonov, A. V.; Brel, V. K.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(7), 1658-9.
Treating Ph2P(O)H with RCCl2NO (R = Et, Pr, Me2CH) in Et2O gave 62-75% Ph2P(O)ON:CClR (same R).


Another Novichok possibility:
Synthesis and the structure of dialkylfluoroformiminophosphates. Martynov, I. V.; Brel, V. K.; Uvarov, V. I.; Yarkov, A. V.; Novikov, V. P.; Chepakova, L. A.; Raevskii, O. A. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (4), 857-60.
Syn- And anti-(RO)2P(O)N:CHF (R = Me, Et, Pr, Bu) were prepd. in 11-25% yields by treating (RO)3P with ClCHFNO2.

Here is some nasty looking stuff that may be of interest:
Reaction of (-aminoalkyl)phosphonates with perfluoro-2-azapropene. Aksinenko, A. Yu.; Pushin, A. N.; Sokolov, V. B.; Gontar, A. F.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (5), 1177-9.
(RO)2P(O)CMeR1N:C:NCF3 (R = Me, R1 = Et; R = Et, R1 = Et, Pr, Bu; R = Me2CHCH2, R1 = Et) were prepd. in 40-60% yields by condensing CF2:NCF3 with (RO)2P(O)CMeR1(NH2) in the presence of KF.

Here is another variant:
Reaction of polychloronitrosoethanes with phosphorous acid derivatives. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (5), 1086-9.
The title reaction gave 20-93% of 22 o-phosphorylated alkyl chloroformimines. Thus, treating ONCCl2R (R = Me, CH2Cl, CHCl2) with (R1O)3P (R1 = Me, Pr, Bu, Me2CHCH2, pentyl, ClCH2CH2) gave (R1O)2P(O)ON:CClR.

Of all the other compounds I have previously referenced this particular compound looks like it may be the deadliest. It has some similarities to most other nerve gasses in that it uses the simplest alkyl groups, and has a direct alkyl and a direct halogen attachment to phosphorus. I would replace those chlorines with fluorine to increase the toxicity:
Reaction of dichloromethylphosphine with 1,1-dichloro-1-nitrosoalkanes. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(7), 1659-60.
MePCl2 reacted with RCCl2NO (R = Et, Pr, Me2CH) in SO2 to give 27-37% RCCl:NOP(O)ClMe.

This compound looks like a good precursor for organophosphorus agents like the previous compound. The chlorines can be replaced by F, and one of the fluorines can form an ester or something else. The second compound is an example of what could be made, and I just bet that stuff is pretty toxic.
Interaction of 2,2,3,3-tetrafluoropropyl dichlorophosphite with 1,1,2-trichloro-1-nitrosoethane. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (6), 1422-3.
Refluxing CHF2CF2CH2OPCl2 (I) with CH2ClCCl2NO (II) in Et2O gave 67.8% Cl2P(O)ON:CClCH2Cl. Treating I with II in SO2 at 20 gave 48.2% (CHF2CF2CH2O)ClP(O)ON:CClCH2Cl.

We might have a real winner with this one as it has similarities with VX nerve gas. The second compound in particular has a =S group. If that could be isomerized, like it is done in making VX, then we have a thioester. The two isobutyl groups are probably too large to make this particular compound all that toxic. I am sure they could be replaced with methyls instead.
Reaction of diisobutylchlorophosphine with 1,1-dichloro-1-nitrosoalkanes in presence of sulfur dioxide and ethyl mercaptan. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (11), 2586-8.
Treating (Me2CHCH2)2PCl with RCCl2NO (R = Me, Et, Pr, Me2CH) in Et2O contg. SO2 gave 61-74% (Me2CHCH2)2P(O)ON:CRCl (same R). When Et2SH was used instead of SO2, 44% (Me2CHCH2)2P(S)ON:CRCl (R = Me) was obtained.

Another phenyl attached compound:
Synthesis and molecular structure of (O-isopropylchloroformimino) diphenylphosphinate. Martynov, I. V.; Chekhlov, A. N.; Ivanov, A. N.; Epishina, T. A.; Makhaev, V. D.; Sokolov, V. B. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (11), 2595-7.
Treating Ph2PH with Me2CHCCl2NO in C6H6 gave 58% Ph2P(O)ON:CClCHMe2, the structure of which was detd. by x-ray crystallog.

This compound has some VX similarities too:
O,O-Dialkyl O-(dialkylformimino) thiophosphates. Chepakova, L. A.; Brel, V. K.; Pushin, A. N.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1987), 57(12), 2716-19.
Twelve (R1O)2P(S)ON:CMeR (R = Me, Et, Pr; R1 = Me, Et, Pr, Bu) were prepd. in 41-62% yields by treating (R1O)2PHS with ONCClMeR or HON:CMeR.

These compounds are similar to the last journal reference except the R and Rí groups are switched. Isomerize that S and we may have something far more toxic.
O-(Alkylchloroformimino) O,O-dialkyl thiophosphates. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1987), (12), 2854-5.
Seven (RO)2P(S)ON:CClR1 (R = Et, Me2CH; R1 = Me, Et, Pr, Me2CH, ClCH2) were prepd. in 33-54% yields by condensing (RO)2PSH with R1Cl2CNO in THF.

Martynov has 64 publications in 1988 alone, his best year. In no particular order here are some highlights:

Molecular and crystal structure of O,O-diethyl 1-[N2-(trifluoromethyl)fluoroformamidino]-1-methylethylphosphonate. Chekhlov, A. N.; Aksinenko, A. Yu.; Sokolov, V. B.; Korenchenko, O. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1988), 302(4), 855-8 [Chem.].
The crystal and mol. structure of (EtO)2P(O)CMe2NHCFNCF3 was detd.

Reaction of (N-acetyl-N-ethylamido)alkylphosphonic acid chlorides with cesium fluoride. Krolevets, A. A.; Adamov, A. V.; Popov, A. G.; Martynov, I. V.. USSR. Zhurnal Obshchei Khimii (1988), 58(11), 2628-9.
RP(O)F(NEtCH:CH2) (R = Me, Me2CH) were prepd. in 45, 50% yields, resp., by treating RPCl(NEtAc) (I) with CsF. I were prepd. in 60, 65% yields, resp., by treating RPCl2 with Me3SiNEtAc.

Stable alkoxyfluorophosphoranes. Krolevets, A. A.; Popov, A. G.; Adamov, A. V.; Martynov, I. V.. USSR. Zhurnal Obshchei Khimii (1988), 58(11), 2626-7.
RPF2(OR1)2 (R = BuCHClCH2, R1 = Me3C; R = Me2CClCH2, R1 = Et) were prepd. in 45, 40% yields, resp., by treating RPF4 with Me3SiOR1.

O-(Alkylchloroformimidoyl) o-alkyl methylphosphonates. Sokolov, V. B.; Ivanov, A. N.; Goreva, T. V.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (5), 1128-30.
Nine (RO)MeP(O)ON:CClR1 (R = Et, Pr, Bu, Me2CH, pentyl; R1 = Me, Et, Pr, Bu, Me2CH) were prepd. in 41-67% yields by treating R1CCl2NO with MeP(OR)2 or MeP(O)H(OR).

Reaction of 1,1-dichloro-1-nitrosoalkanes with phosphorus(III) chlorides. Martynov, I. V.; Ivanov, A. N.; Epishina, T. A.; Sokolov, V. B. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (9), 2128-32.
The title reaction was studied. Thus, R1R2P(O)ON:CRCl (R = Me, Et, Pr, Me2CH; R1 = R2 = Cl, Me2CHCH2; R1 = Cl, R2 = Me) were prepd. in 34-74% yields by reaction of RCCl2NO with R1R2PCl in the presence of SO2.

Synthesis and x-ray diffraction study of N-(diisopropoxythiophosphoryl)thioacetamide. Solov'ev, V. N.; Chekhlov, A. N.; Zabirov, N. G.; Cherkasov, R. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1988), 300(6), 1386-9 [Chem.].
Treating MeCSNH2 with Me3COK in MeCN and then with ClP(S)(OCHMe2)2 gave 15% MeCSNHP(S)(OCHMe2)2, the structure of which was detd. by x-ray crystallog.

Reaction of 1,1-dichloro-1-nitrosoethane with phosphorus oxychloride in the presence of zinc. Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (7), 1691.
Cl2P(O)ON:CClMe was prepd. in 26.6% yield by treating MeCCl2NO with POCl3 in the presence of Zn.

Comparative studies on the interaction of acetylcholinesterases from human erythrocytes and housefly heads with phosphorylated alkylchloroformoxims. Shataeva, G. A.; Makhaeva, G. F.; Yankovskaya, V. L.; Sokolov, V. B.; Ivanov, A. N.; Martynov, I. V.. Inst. Physiol. Act. Subst., Chernogolovka, USSR. Zhurnal Evolyutsionnoi Biokhimii i Fiziologii (1988), 24(6), 791-6.
Among Valexon analogs, 6 (RO)2P(O)ON:CClMe (I), 6 (RO)2P(O)ON:C(Cl)CH2Cl (II), and 5 (RO)2P(O)ON:C(Cl)CHCl2 (III, R = Me, Et, Pr, iso-Bu, Bu, amyl), and 4 (EtO)2P(O)ON:C(Cl)R1 (IV, R1 = Me, Et, Pr, Bu), I-III (R = Et) were highly selective insecticides, having rate consts. of bimol. reaction with acetylcholinesterase (KII) of human erythrocytes (HE) lower by 1 magnitude order than with that from housefly heads (FL). Inhibition of both HE and FL followed the order I < II < III. Phosphorylation capacity of II 1.6-fold exceeded that of I. Replacing Me by Et, increased the effect of I-III on FL 3-8-fold and decreased that on HE 1.7-4-fold. Further increases in hydrophobicity abolished the specificity of I-III. The selectivity of IV decreased in order of R1: Me > Et > Bu; IV (R1 = Pr) showed no selectivity.

Fluorination of some phosphoric acid derivatives. Zavorin, S. I.; Lermontov, S. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka., USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1988), (5), 1174-6.
Dialkyl fluorophosphates were prepd. by the title fluorination with Et3N.3HF (I). Thus, fluorination of (EtO)2P(O)ON:CCl2 with I in MeCN gave 83.5% (EtO)2P(O)F.

Reaction of fluorine-containing acetylenic alcohols with phosphorus trichloride. Brel, V. K.; Chekhlov, A. N.; Ionin, B. I.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1988), 58(4), 750-7.
Treating RC.tplbond.CCMe(OH)CH2F (I; R = Ph) with PCl3 in Et2O gave 45% Cl2P(O)CR:C:CMeCH2F (II; R = Ph) and 24% E- and Z-Cl2P(O)CHPhCCl:CMeCH2F (III). Under the same conditions, I (R = MeOCH2) gave a mixt. of II (R = MeOCH2) and Cl2P(O)C(:CH2)CCl:CMeCH2F. Treating I (R = Ph) with MeOH and then with Br2 gave oxaphospholene IV. The structure of III was detd. by x-ray crystallog.

Synthesis and anticholinesterase activity of fluorochloronitroacetic acid thioesters. Ivanov, Yu. Ya.; Uvarov, V. I.; Brel, V. K.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1988), 22(5), 538-40.
Treating O2NCFClCOX (I; X = OH) with PCl5 gave I (X = Cl), which reacted with RSH (R = Et, Bu) to give 35-55% I (X = SR; same R) (II). II were less effective acetylcholinesterase inhibitors than I (X = OR; same R) but had comparable activity vs. butyrylcholinesterase with lower toxicity.

Synthesis and antiesterase activity of sulfur-containing phosphorylated oximes. Chepakova, L. A.; Bret, V. K.; Makheva, G. F.; Yankovskaya, V. L.; Beznosko, B. K.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1988), 22(2), 143-6.
Reaction of (RS)2POEt (R = Et, Pr, iso-Bu, Bu or amyl) with O:NCFCl2 gave the corresponding (RS)2P(:O)ON:CClF (I). An increase in the hydrophobicity of I did not alter the anticholinesterase activity of I, while the butyrylcholinesterase and carboxylesterase activity were increased.

O-substituted alkylchloroformoximes as substrates and inhibitors of cholinesterases. Ivanov Iu Ia; Sokolov V B; Epishina T A; Martynov I V Doklady Akademii nauk SSSR (1990), 310(5), 1253-5.

Inhibition of cholinesterase activity with fluorine-containing derivatives of alpha-aminophosphonic acid. Kuusk V V; Morozova I V; Agabekian R S; Aksinenko A Iu; Epishina T A; Sokolov V B; Kovaleva N V; Razdol'skiy A N; Fetisov V N; Martynov I V Bioorganicheskaia khimiia (1990 Nov), 16(11), 1500-8.
A series of O,O-diethyl-1-(N-alpha-hydrohexafluoroisobutyryl)aminoalkylphos phonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate constants and the enzyme-inhibitor intermediate dissociation constants are calculated. The quantitative structure-activity relationships including both hydrophobic and calculated steric parameters of substituents are developed for APh--ChE interactions. Molecular mechanics (programme MM2) was used for determining steric parameters (Es). On the basis of QSAR models analysis it was concluded that hydrophobic interactions play an essential role in APh--AChE binding, whereas for APh--BuChE binding steric interactions are essential. Presence of at least two APh binding centres on the surface of AChE and BuChE is suggested.

Reaction of 1,1-dichloro-1-nitrosobutane with (N,N-dimethylamido)dichlorophosphite. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (6), 1416-18.
Reaction of PrCCl2NO with Me2NPCl2 in Et2O or in SO2 gave 36% Me2NPCl4 or 30% Me2NP(O)ClON:CClPr, resp. Treating Me2NPCl4 with SO2 gave 91% Me2NP(O)Cl2. Reaction of PrCCl2NO with Me2NPCl2 in Et2O, and then with Ph3P and distn. gave Ph3PO and PrCN.

Alkyl chlorofluoroformimino perfluoroalkylphosphonates. Chepakova, L. A.; Brel, V. K.; Martynov, I. V.; Maslennikov, I. G. Inst. Fiziol. Akt. Veshchestv., Chernogolovka, USSR. Zhurnal Obshchei Khimii (1989), 59(6), 1455-6.
Treating RP(OR1)2 (R = CF3, R1 = Pr, Bu; R = CF3CF2, R1 = Me, Bu) with CFCl2NO in Et2O gave 76-88% title compds. R1OP(O)RON:CFCl.

Synthesis of dialkyl (3-alkyl-1,3-alkadien-2-yl)phosphonates. Brel, V. K.; Abramkin, E. V.; Martynov, I. V.; Ionin, B. I. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1989), 59(9), 2142-3.
(RO)2P(O)C(:CH2)CR1:CMe2 (R = Et, Pr; R1 = Me, Et) were prepd. in 41-73% yields by the Grignard reaction of (RO)2P(O)C(CH2OMe):C:CMe2 with R1X (X = halo).

Synthesis and antiesterase activity of O,O-dialkyl S-(ethoxycarboxyl)chloromethyl thiophosphates. Khaskin, B. A.; Makhaeva, G. F.; Torgasheva, N. A.; Ishmuratov, A. S.; Yankovskaya, V. L.; Fetisov, V. I.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovko, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (12), 2741-6.
The title compds. (RO)2P(O)SCHClCO2Et (I; R = alkyl homologs) were prepd. in 82-95% yields in the reaction of (RO)2P(O)SCl with N2CHCO2Et at -25 (in Et2O) or 6-7 (in benzene), presumably via a noncarbene mechanism. I irreversibly inhibited acetylcholinesterase, butyrylcholinesterase, and carboxylesterase; antibutyrylcholinesterase activity increased in the homologous series of R, with max. at R = Bu. An antiesterase MSBAR of I was fulfilled with parameters representing hydrophobicity and steric properties of R.

Synthesis and cholinesterase hydrolysis of O-acylated alkylchloroformoximes. Sokolov, V. B.; Ivanov, Yu. Ya.; Epishina, T. A.; Agabekyan, R. S.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1989), 23(11), 1317-20.
The title compds., RCO2N:CClR1 (R = Me, Et, Pr or CH2Cl and R1 = Me, Et, Pr, or iso-Pr) were prepd. e.g., by the reaction of 1,1-dichloro-1-nitrosobutane with AcCl in the presence of Zn. These compds. were good substrates for acetyl- and butyrylcholinesterases. The kinetic parameters (Km, Vmax and ac) of these compds. in the hydrolysis reactions were comparable to those with acetylcholine. The acute toxicity was 79-381 mg/kg in mice given drugs orally.

Synthesis and structure of O,O-dialkyl 2-[(ethoxycarbonyl)amino]hexafluoroisopropylphosphonates. Aksinenko, A. Yu.; Chekhlov, A. N.; Korenchenko, O. V.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1990), 60(1), 61-5.
The title compds. (RO)2P(O)C(CF3)2NHCO2Et (I; R = Me, Et, CHMe2) were prepd. in 54-76% yields in the reaction of (RO)2P(O)H with (CF3)2C:NCO2Et. The crystal and mol. structure of I (R = Et) was detd.

O-Substituted alkylchloroformoximes as substrates and inhibitors of cholinesterases. Ivanov, Yu. Ya.; Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Aktivn. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1990), 310(5), 1253-5 [Biochem.].
The ability of O-substituted alkylchloroformoximes to serve as substrates for acetylcholinesterase (ACE, EC 3.1.1.7) and butyrylcholinesterase (BCE, EC 3.1.1.8) and to inhibit acetylcholine hydrolysis by these enzymes was detd., along with the LD50 of these compds. in mice. The compds. tested were O-acylated alkylchloroformoximes of the general formula R1C(O)ON:C(Cl)R2 [R1 = R2 = Me; R1 = Me, R2 = Et; R1 = Me, R2 = Pr; R1 = Et, R2 = Me; R1 = Et, R2 = iso-Pr; R1 = Pr, R2 = iso-Pr; R1 = CH2Cl, R2 = Pr (I); R1 = CH2Cl, R2 = iso-Pr (II)], O-carbonylated alkylchloroformoximes of the general formula EtOC(O)ON:C(Cl)R [R = Me (III), iso-Pr (IV)], and O-carbamoylated alkylchloroformoximes of the general formula (Me)2NC(O)ON:C(Cl)R [R = Me (V), iso-Pr (VI)]. All of the compds. except for I and II were good substrates for the enzymes, with Km values for ACE ranging (0.3-11.0)  10-4M and for BCE ranging (0.5-13.0)  10-4M (the Km values of ACE and BCE with acetylcholine were 1.3  10-4 and 5.4  10-4M, resp.). III and IV were competitive (Ki 1.6  10-4M) and mixed-type (Ki 4.2  10-4M) inhibitors, resp., of ACE. V and VI were effective inhibitors of both ACE and BCE, with bimol. rate consts. for inhibition (kII) of 5.7  103 and 1.4  105 M-1 min-1, resp., for ACE, and 9.8  103 and 5.4  106 M-1 min-1, resp., for BCE. The LD50 values for the tested compds. ranged 60-381 mg/kg body wt.

O-(alkylchloroformimino)(methyl)thiophosphonic acid chlorides. Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1989), (12), 2865-6.
Treating the adduct from RCCl2NO and MePCl2 with H2S gave 21-35% MeP(S)ClON:CRCl.

Interaction of 1,1-dichloro-1-nitrosoalkanes with S-ethylmethylphosphonous chloride in the presence of sulfur dioxide. Sokolov, V. B.; Ivanov, A. N.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1990), (2), 464-5.
EtSP(O)MeON:CClR (R = Me, Et, Pr) were prepd. in 42-47% yields by treating RCCl2NO with EtSPMeCl in the presence of SO2.

O-(alkylchloroformimino)-O-alkylphosphoric acid chlorides. Sokolov, V. B.; Ivanov, A. N.; Goreva, T. V.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1990), (5), 1122-5.
Reaction of (ON)CCl2R with (R'O)2PCl (R, R' = alkyl) afforded the title compds. (R'O)ClP(O)ON:CRCl (I) in up to 69% yield. Hydrolysis of I led to substitution of P-, and not C-bound Cl, resulting in (R'O)(NH4O)P(O)ON:CRCl.

Reaction of the adduct of methyldichlorophosphine and 1,1-dichloro-1-nitrosoethane with thioacetic acid. Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Zhurnal Obshchei Khimii (1990), 60(8), 1923-4.
Treating MePCl2 with MeCCl2NO in PhMe, followed by addn of 1 or 2 equiv AcSH gave 56% MeP(S)ClON:CMeCl or 32% MeP(S)ClON:CMeSAc, resp.

Inhibition of cholinesterase activity by fluorine-containing derivatives of -aminoalkylphosphonic acids. Kuusk, V. V.; Morozova, I. V.; Agabekyan, R. S.; Aksinenko, A. Yu.; Epishina, T. A.; Sokolov, V. B.; Kovaleva, N. V.; Razdol'skii, A. N.; Fetisov, V. I.; Martynov, I. V.. Inst. Physiol. Act. Subst., Chernogolovka, USSR. Bioorganicheskaya Khimiya (1990), 16(11), 1500-8.
A series of O,O-diethyl-1-(N--hydrohexafluoroisobutyryl)aminoalkylphosphonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate consts. and the enzyme-inhibitor intermediate dissocn. consts. are calcd. The quant. structure-activity relationships including both hydrophobic and calcd. steric parameters of substituents are developed for APh-ChE interactions. Mol. mechanics (program MM2) was used for detg. steric parameters (Es). On the basis of QSAR models anal. it was concluded that hydrophobic interactions play an essential role in APh-AChE binding, whereas for APh-BuChE binding steric interactions are essential. Presence of at least two APh binding centers on the surface of AChE and BuChE is suggested.

Synthesis and anticholinesterase activity of O-carbamoylated alkylchloroform oximes. Sokolov, V. B.; Ivanov, Yu. Ya.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshestva, Chernogolovka, USSR. Khimiko-Farmatsevticheskii Zhurnal (1991), 25(4), 33-4.
Treating ClCO2N:CClR (R = Me, Et, Pr, CHMe2) with NHR1R2 (R1 = R2 = H, Me, Et; R1 = H, R2 = Me) in Et2O gave 50-69% R1R2NCO2N:CClR (same R-R3), which are acetyl- and butyrylcholinesterase inhibitors (k11 = 1.1  10-2 to 5.4  10-6 M-1 min-1). Acute oral toxicity in mice ranged from 32 to 565 mg/kg.

O-Alkyl O-methylchloroformimino phenylphosphonates - effective inhibitors of the hen brain neurotoxic esterase. Makhaeva, G. F.; Kononova, I. V.; Malygin, V. V.; Lyashenko, Yu. E.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, USSR. Doklady Akademii Nauk SSSR (1991), 317(4), 1009-12 [Biochem.].
The title phosphonates were effective inhibitors of neurotoxic esterase; with increasing hydrophobicity the compds. showed pronounced and selective biol. activity towards brain neurotoxic esterase compared to acetylcholinesterase. Thus, the structure of phenylphosphonate played a major role in the inhibitory effects of these potential pesticides towards neurotoxic esterase or acetylcholinesterase.

Synthesis and anticholinesterase activity of fluorine-containing -aminophosphoryl compounds. Korenchenko, O. V.; Ivanov, Yu. Ya.; Aksinenko, A. Yu.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Khimiko-Farmatsevticheskii Zhurnal (1992), 26(6), 21-3.
Reaction of R2P(O)H (R = MeO, EtO, PrO, Me2CHO, Ph) with (CF3)2C:NCOR1 (R1 = OEt, OCH2Ph, OPr, OBu, OCH2CH2CHMe2, CF3) in Et2O gave 44-93% R2P(O)C(CF3)2NHCOR1. Treating a 1,4,2-oxazaphospholine deriv. with alcs. gave Me(R)P(O)C(CF3)2NHCO2Et (R = BuO, Me2CHO). Bimol. rate consts. for inhibition of cholinesterases by these compds. were detd.

Synthesis and insecticidal and acaricidal activity of O-alkylchloroformimine O,O-dialkyl phosphates and O,O-dialkylthiophosphates. Ivanov, A. M.; Ivanova, G. B.; Sokolova, V. B.; Epishina, T. N.; Goreva, T. V.; Beznosko, B. K.; Martynov, I. V.. Inst. Fiziol. Okl. Veshchestv., Chernogolovka, Russia. Fiziologicheski Aktivnye Veshchestva (1991), 23 58-62.
Of 26 title compds., those having ethoxy group at P were both insecticides and acaricides, whereas those having their methoxy group showed insecticidal activity only. Increasing hydrophobicity of the alkoxy substituents decreased i.m. toxicity to mice, but also the effectiveness. O replacement by S also decreased toxicity. Synthesis is indicated.

Paradoxical toxic effect and calcium antagonism of the cholinesterase inhibitors O-(N-arylcarbamoyl)acylhydroximoyl chlorides. Ivanov, Yu. Ya.; Sokolov, V. B.; Epishina, T. A.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Doklady Akademii Nauk (1993), 328(6), 744-6 [Biochem.].
N-phenylcarbamates and aliph. analogs of the formula R R1N(O)ON::C(Cl)R2 [where R = Et, Me, and Ph; R1 = H, Me; R2 = Et, Pr, iso-Pr] were examd. for their acetylcholinesterase and butyrylcholinesterase inhibition, for their acute toxicity and their action on selective organs. The enzyme inhibition depended on their mol. structure. Paradoxical effects (higher dose and low toxicity and vice versa) were noted.

Similar sensitivity of rat and hen brain neurotoxic esterase to inhibition by O-alkyl-O-alkylchloroformiminophenylphosphonates. Makhaeva, G. F.; Filonenko, I. V.; Malygin, V. V.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Chernogolovka, Russia. Doklady Akademii Nauk (1993), 332(5), 650-3.
Quant. structure-neurotoxic esterase (NTE)-inhibiting activity relationship of the title phosphonates was examd. against both rat and chicken enzyme. The phosphonates effectively inhibited the enzyme from both the sources. The anti-NTE activity of the compds. increased with the length of alkyl radical in the phosphoryl portion. The introduction of branched substituent, esp. in the -position, decreased the antienzyme activity. Math. equations are derived to describe the effects of steric factors on the NTE inhibition. PI50 = -lg I50, where I50 is the concn. of the inhibitor required to cause 50% inhibition, was calcd. for these compds.; the values are tabulated.

Crystal and molecular structures and synthesis of O,O-diisopentyl 1-(phenylsulfonamido)-1-(trifluoromethyl)-2,2,2-trifluoroethylphosphonate. Chekhlov, A. N.; Aksinenko, A. Yu.; Sokolov, V. B.; Martynov, I. V.. Inst. Fiziol. Akt. Veshchestv, Ross. Akad. Nauk, Chernogolovka, Russia. Doklady Akademii Nauk (1995), 345(3), 360-363.
Reaction of (CF3)2C:NSO2Ph and (Me2CHCH2CH2O)2P(O)H in Et2O gave 85% title compd. (Me2CHCH2CH2O)2P(O)C(CF3)2NHSO2Ph, the structure of which was detd. by x-ray crystallog.

Assessment of the neurotoxic potential of some methyl- and phenylphosphonates using a stable preparation of neuropathy target esterase from chicken brain. Makhaeva G F; Malygin V V; Martynov I V Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Moscow Oblast, 142432 Russia Doklady. Biochemistry and biophysics (2001 Mar-Apr), 377 68-71.

simply RED
April 16th, 2005, 06:16 AM
The sulphur, like nitrogen, phosphorous ..... exists in quaternized form.
Anyway, strong methylating agent like dimethy sulphate is needed to quaternize it.

NH3 + BrCH3 = CH3NH3+Br-

CH3SH + (CH3)2SO4 = (CH3)2SH+ CH3SO4-

It is not a type mistake!
Anyway, these compound are sold as pesticides

http://environmentalchemistry.com/yogi/chemicals/cn/Demeton.html
http://www.inchem.org/documents/pds/pds/pest60_e.htm
http://www.inchem.org/documents/jmpr/jmpmono/v065pr15.htm
http://www.hclrss.demon.co.uk/demeton-s.html

systox, demeton ....

So we have VX with only one reaction. Just buy the pesticide, purify the
main ingredient, dissolve in THF or ether and add the dimethyl sulphate.
(C2H5O)2P=OSC2H4-S-C2H5 + (CH3)2SO4 =
(C2H5O)2P=OSC2H4-(S+)-(C2H5)(CH3) CH3SO4(-)
Toxicity LD50 = 0,017 mg/kg !!!!!!!!!!!!!!!!
With dietyl sulphate LD50 = 0,01 !
If the solvent contains no OH groups... Add the dimethyl sulphate directly!

" Quaternizing the sulphur we have structure maximal near "choline with quaternized nitrogen". Sulphur does the task of fluorine as it is easily hydrolisable by the enzyme . (my colegues tried to explain why it works so good - hahahaha ) "

Actually i never tried it, but everything elese in this report was 100% true plus things i tried myself ....


" THE PARTICULAR SULPHUR VX COMPOUNDS WERE 100-1000 TIMES MORE EASILY ABSORBED THROUGH THE SKIN THAN ESERINE AND SOMAN. 100MG SOMAN CAUSED DEATH AS WE COMPLETED WITH 5MG GD - 42 "
{{{{{{hm.... it is only 20 heh...}}}}}}

" BEWARE ! 5 MILIGRAMS VX ON THE SKIN CAUSES DEATH ! THIS PARTICULAR VX DOES NOT HYDROLISE BEFORE PH 10 !!! "

" THE BEST ANTIDOTE WE TRIED DEMINISHED THE TOXICITY ONLY TWO TIMES - SO - WE CONSIDER NO ANTIDOTE EXISTS FOR THE UPPER COMPOUNDS "


" INJECTING MEDETFK INTER-VEINS OR INTER-MUSCULAR CAUSED IMMEDIATE DEATH "
{{{{{ sure, I tried BI - 58 (dimetoate) with the same resault }}}}}

p.s. The report continues with psycho chemical experiments but i found nothing of any interest there ... (the trivial compounds - LSD, mescaline, neavy amfetamine molecules ... )

simply RED
April 16th, 2005, 06:16 AM
The sulphur, like nitrogen, phosphorous ..... exists in quaternized form.
Anyway, strong methylating agent like dimethy sulphate is needed to quaternize it.

NH3 + BrCH3 = CH3NH3+Br-

CH3SH + (CH3)2SO4 = (CH3)2SH+ CH3SO4-

It is not a type mistake!
Anyway, these compound are sold as pesticides

http://environmentalchemistry.com/yogi/chemicals/cn/Demeton.html
http://www.inchem.org/documents/pds/pds/pest60_e.htm
http://www.inchem.org/documents/jmpr/jmpmono/v065pr15.htm
http://www.hclrss.demon.co.uk/demeton-s.html

systox, demeton ....

So we have VX with only one reaction. Just buy the pesticide, purify the
main ingredient, dissolve in THF or ether and add the dimethyl sulphate.
(C2H5O)2P=OSC2H4-S-C2H5 + (CH3)2SO4 =
(C2H5O)2P=OSC2H4-(S+)-(C2H5)(CH3) CH3SO4(-)
Toxicity LD50 = 0,017 mg/kg !!!!!!!!!!!!!!!!
With dietyl sulphate LD50 = 0,01 !
If the solvent contains no OH groups... Add the dimethyl sulphate directly!

" Quaternizing the sulphur we have structure maximal near "choline with quaternized nitrogen". Sulphur does the task of fluorine as it is easily hydrolisable by the enzyme . (my colegues tried to explain why it works so good - hahahaha ) "

Actually i never tried it, but everything elese in this report was 100% true plus things i tried myself ....


" THE PARTICULAR SULPHUR VX COMPOUNDS WERE 100-1000 TIMES MORE EASILY ABSORBED THROUGH THE SKIN THAN ESERINE AND SOMAN. 100MG SOMAN CAUSED DEATH AS WE COMPLETED WITH 5MG GD - 42 "
{{{{{{hm.... it is only 20 heh...}}}}}}

" BEWARE ! 5 MILIGRAMS VX ON THE SKIN CAUSES DEATH ! THIS PARTICULAR VX DOES NOT HYDROLISE BEFORE PH 10 !!! "

" THE BEST ANTIDOTE WE TRIED DEMINISHED THE TOXICITY ONLY TWO TIMES - SO - WE CONSIDER NO ANTIDOTE EXISTS FOR THE UPPER COMPOUNDS "


" INJECTING MEDETFK INTER-VEINS OR INTER-MUSCULAR CAUSED IMMEDIATE DEATH "
{{{{{ sure, I tried BI - 58 (dimetoate) with the same resault }}}}}

p.s. The report continues with psycho chemical experiments but i found nothing of any interest there ... (the trivial compounds - LSD, mescaline, neavy amfetamine molecules ... )

simply RED
April 16th, 2005, 06:16 AM
The sulphur, like nitrogen, phosphorous ..... exists in quaternized form.
Anyway, strong methylating agent like dimethy sulphate is needed to quaternize it.

NH3 + BrCH3 = CH3NH3+Br-

CH3SH + (CH3)2SO4 = (CH3)2SH+ CH3SO4-

It is not a type mistake!
Anyway, these compound are sold as pesticides

http://environmentalchemistry.com/yogi/chemicals/cn/Demeton.html
http://www.inchem.org/documents/pds/pds/pest60_e.htm
http://www.inchem.org/documents/jmpr/jmpmono/v065pr15.htm
http://www.hclrss.demon.co.uk/demeton-s.html

systox, demeton ....

So we have VX with only one reaction. Just buy the pesticide, purify the
main ingredient, dissolve in THF or ether and add the dimethyl sulphate.
(C2H5O)2P=OSC2H4-S-C2H5 + (CH3)2SO4 =
(C2H5O)2P=OSC2H4-(S+)-(C2H5)(CH3) CH3SO4(-)
Toxicity LD50 = 0,017 mg/kg !!!!!!!!!!!!!!!!
With dietyl sulphate LD50 = 0,01 !
If the solvent contains no OH groups... Add the dimethyl sulphate directly!

" Quaternizing the sulphur we have structure maximal near "choline with quaternized nitrogen". Sulphur does the task of fluorine as it is easily hydrolisable by the enzyme . (my colegues tried to explain why it works so good - hahahaha ) "

Actually i never tried it, but everything elese in this report was 100% true plus things i tried myself ....


" THE PARTICULAR SULPHUR VX COMPOUNDS WERE 100-1000 TIMES MORE EASILY ABSORBED THROUGH THE SKIN THAN ESERINE AND SOMAN. 100MG SOMAN CAUSED DEATH AS WE COMPLETED WITH 5MG GD - 42 "
{{{{{{hm.... it is only 20 heh...}}}}}}

" BEWARE ! 5 MILIGRAMS VX ON THE SKIN CAUSES DEATH ! THIS PARTICULAR VX DOES NOT HYDROLISE BEFORE PH 10 !!! "

" THE BEST ANTIDOTE WE TRIED DEMINISHED THE TOXICITY ONLY TWO TIMES - SO - WE CONSIDER NO ANTIDOTE EXISTS FOR THE UPPER COMPOUNDS "


" INJECTING MEDETFK INTER-VEINS OR INTER-MUSCULAR CAUSED IMMEDIATE DEATH "
{{{{{ sure, I tried BI - 58 (dimetoate) with the same resault }}}}}

p.s. The report continues with psycho chemical experiments but i found nothing of any interest there ... (the trivial compounds - LSD, mescaline, neavy amfetamine molecules ... )

simply RED
April 16th, 2005, 05:48 PM
GD-42 was found in the net also ...

http://www.rand.org/publications/MR/MR1018.5/MR1018.5.chap4.html

Gd-42 (O-ethyl S-2-(S'S'-methylethylsulphonio)ethyl methylphosphonothiolate methosulphate)

(C2H50)(CH3)(P=O)-S-CH2-CH2-(S+)(CH3)(C2H5) SO4CH3(-)
Right :) ...