Phosphorylacetic acid thioamides as key substances for phosphorylated heterocycles

Article abstract of DOI:10.1080/10426500701807152

Diethoxyphosphorylthioacetamide in a reaction with 2,3-dichloroquinoxaline acted as a thionating reagent, giving diethoxyphosphorylacetonitrile and 2-chloro-3-[(3-chloro-2-quinoxalinyl)-thio]quinoxaline. Base-catalyzed reactions of phosphorythioacetamides with N-methylquinoxalinium iodide proceeded stereoselectively to yield cis-3-phosphoryl-1,3,3a,4,9,9a-hexahydro-2H-pynola[2, 3-b]quinoxaline-2-thiones. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500701807152

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Phosphorylacetic Acid
Thioamides As Key Substances
for Phosphorylated
Heterocycles
V. A. Kozlov a , I. L. Odinets a , D. V. Aleksanyan a ,
P. V. Petrovskii a & T. A. Mastryukova a
a A. N. Nesmeyanov Institute of Organoelement
compounds RAS , Moscow, Russia
Published online: 21 Jun 2008.
To cite this article: V. A. Kozlov , I. L. Odinets , D. V. Aleksanyan , P. V. Petrovskii
& T. A. Mastryukova (2008) Phosphorylacetic Acid Thioamides As Key Substances
for Phosphorylated Heterocycles, Phosphorus, Sulfur, and Silicon and the Related
Elements, 183:2-3, 683-684, DOI: 10.1080/10426500701807152
To link to this article: http://dx.doi.org/10.1080/10426500701807152
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Phosphorus, Sulfur, and Silicon, 183:683–684, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701807152
Phosphorylacetic Acid Thioamides As Key Substances for
Phosphorylated Heterocycles
V. A. Kozlov, I. L. Odinets, D. V. Aleksanyan,
P. V. Petrovskii, and T. A. Mastryukova
A. N. Nesmeyanov Institute of Organoelement compounds RAS,
Moscow, Russia
Diethoxyphosphorylthioacetamide in a reaction with 2,3-dichloroquinoxaline acted
as a thionating reagent, giving diethoxyphosphorylacetonitrile and 2-chloro-3-
[(3-chloro-2-quinoxalinyl)-thio]quinoxaline. Base-catalyzed reactions of phospho-
rythioacetamides with N-methylquinoxalinium iodide proceeded stereoselectively
to yield cis-3-phosphoryl-1,3,3a,4,9,9a-hexahydro-2H-pynola[2,3-b]quinoxaline-2-
thiones.
Keywords 1,3,3a,4,9,9a-hexahydro-2H-pyrrolo[2,3-b]quinoxaline-2-thiones; 2,3-dich-
loroquinoxaline; annulation; N-methylquinoxalinium iodide; phosphorythioacetamides
Thioamides served as building blocks to obtain heterocycles of phar-
maceutical importance. Recently we elaborated the facile synthetic
route to phosphorus-substituted carboxylic acid thioamides1 (PTA)
and demonstrated their application in regioselective heterocyclization
with dimethyl acetylendicarboxylate leading to phosphorus containing
thiazolidin-4-ones as potential drug candidates.2 Since azines contain-
ing two or more heteroatoms undergo annelation with various bisnu-
cleophilic reagents3 leading to annulated heterocycles possessing bi-
ological activity, we investigated the ability of PTA to play a role as
annelating agents in such reactions.
SCHEME 1
683

684
V. A. Kozlov et al.
It was found that interacting with 2,3-dichloroquinoxaline thioamide
1a served as thionation agent, resulting in bis(quinoxalinyl)sulfide
2 and phosphorylacetonitrile instead of the expected thiazolo[4,5-
b]quinoxaline. The interaction of PTA with N-methylquinoxalinium
iodide proceeded as annelation but resulted in 3-phosphorylated
thiolactames, namely cis-1,3,3a,4,9,9a-hexahydro-2H-pyrrolo[2,3-
b]quinoxaline-2-thiones 3a, b, in contrast to the similar reactions of
non-phosphorylated thioamides giving thiazole derivatives.
To compare the reactivity of phosphorylated acetic acid amides and
thioamides we tried to accomplish a similar transformation using
(EtO)2P(O)CH2C(O)NH2. But CH-acidity of the latter was found to be
insufficient for addition to the quinoxaline derivative, and the start-
ing phosphorus containing substrate was retrieved from the reaction
mixture.
Taking into account that derivatives of carboxylic acid thioamides
are inclined to various hetrocyclizations similar to thioamides them-
selves, we attempted to obtain enamine that was useful for further syn-
thesis of phosphorylated pyrimidinethione. However, treatment of 1b
with N(dimethoxymethyl)-N,N-dimethylamine resulted in S-alkylation
product 4, which does not react with phenyl hydrazine.
SCHEME 2
Therefore, research of phosphorylacetic acid thioamides’ reactivity
has revealed that these compounds can serve as thionating agents,
C,N-, S,N-, or S-nucleophiles, depending on the substrate’s structure.
REFERENCES
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Bull., 53, 925 (2004)].
[2] V. A. Kozlov, I. L. Odinets, K. A. Lyssenko, S. G. Churusova, S. V. Yarovenko, P. V.
Petrovskii, and T. A. Mastryukova, Heteroatom. Chem., 2, 159 (2005).
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