Dithiophosphoric and dithiophosphonic acids and their derivatives on the basis of thymol: Synthesis and antimicrobial activity

Article abstract of DOI:10.1080/10426507.2012.740697

Biologically active dithiophosphoric and dithiophosphonic acids, their ammonium salts as well as S-silyl and S-plumbyl derivatives were prepared by the reaction of thymol with tetraphosphorus decasulfide and 2,4-diaryl 1,3,2,4-dithiadiphosphetane-2,4-disu

Full text of DOI:10.1080/10426507.2012.740697

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Phosphorus, Sulfur, and Silicon and the Related
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Dithiophosphoric and Dithiophosphonic Acids and Their
Derivatives on the Basis of Thymol: Synthesis and
Antimicrobial Activity
Rafael A. Cherkasov a , Ilyas S. Nizamov a b , Gulnara T. Gabdullina a , Lyubov A. Almetkina a
, Radik R. Shamilov a & Artem V. Sofronov a
a Kazan Federal University, Kazan, Russia
b State Budgetary-Funded Institution of Science, A. E. Arbuzov Institute of Organic and
Physical Chemistry of Kazan, Scientific Center of Russian Academy of Sciences, Kazan,
Russia
Accepted author version posted online: 01 Nov 2012.
To cite this article: Rafael A. Cherkasov, Ilyas S. Nizamov, Gulnara T. Gabdullina, Lyubov A. Almetkina, Radik R.
Shamilov & Artem V. Sofronov (2012): Dithiophosphoric and Dithiophosphonic Acids and Their Derivatives on the
Basis of Thymol: Synthesis and Antimicrobial Activity, Phosphorus, Sulfur, and Silicon and the Related Elements,
DOI:10.1080/10426507.2012.740697
To link to this article: http://dx.doi.org/10.1080/10426507.2012.740697
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ACCEPTED MANUSCRIPT
DITHIOPHOSPHORIC AND DITHIOPHOSPHONIC ACIDS AND THEIR
DERIVATIVES ON THE BASIS OF THYMOL: SYNTHESIS AND
ANTIMICROBIAL ACTIVITY
Rafael A. Cherkasov,1 Ilyas S. Nizamov*,1,2 Gulnara T. Gabdullina,1 Lyubov A. Almetkina,1
Radik R. Shamilov1 and Artem V. Sofronov1
1 Kazan Federal University, Kazan, Russia
2 State Budgetary-Funded Institution of Science, A. E. Arbuzov Institute of Organic and Physical
Chemistry of Kazan, Scientific Center of Russian Academy of Sciences, Kazan, Russia
*Address correspondence to Ilyas S. Nizamov, Kazan Federal University, Kremlievskaya, 18,
Kazan 420008, Russia. Email: isnizamov@mail.ru
Keywords: Thymol; tetraphosphorus decasulfide; 2,4-diaryl 1,3,2,4-dithiadiphosphetane-2,4-di-
sulfides; dithiophosphoric acids; dithiophosphonic acids
Abstract: Biologically active dithiophosphoric and dithiophosphonic acids, their ammonium
salts as well as S-silyl and S-plumbyl derivatives were prepared by the reaction of thymol with
tetraphosphorus decasulfide and 2,4-diaryl 1,3,2,4-dithiadiphosphetane-2,4-disulfides.
1
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INTRODUCTION
Organothiophosphorus compounds containing pharmacophoric functionalities in O-
aromatic substituents at the tetracoordinated phosphorus atom seem to possess appreciable
biological activity. Phenols and its homologues are known to act and are used as antiseptic
agents. We have studied thiophosphorylation reaction of thymol as one the most accessible
aromatic terpeniol by tetraphosphorus decasulfide and 2,4-diaryl 1,3,2,4-dithiadiphosphetane-
2,4-disulfides.
RESULTS AND DISCUSSION
Tetraphosphorus decasulfide was allowed to react with thymol in benzene at 50 °C for 2
h to form O,O-bis(2-iso-propyl-5-methylphen-1-yl) dithiophosphoric acid (Р = 77 ppm), which
was transformed into the corresponding ammonium salt (Р = 106 ppm, m.p.: 51 °C), Scheme 1.
To prepare biologically active ammonium dithiophosphates the O,O-bis(2-iso-propyl-5-
methylphen-1-yl) dithiophosphoric acid obtained was treated with enantiopure (S)-(-)--
phenylethylamine (Scheme 2), its racemate as well as with bisphenyleneamine.
2
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2,4-Diaryl 1,3,2,4-dithiadiphosphetane-2,4-disulfides react with thymol at 50 °C during 1
h to yield corresponding aryldithiophosphonic acids (Р = 86 ppm). These thioacids were
transformed into the corresponding ammonium salts (Р = 108 – 109 ppm) by reaction with
ammonia or racemic -phenylethylamine.
NH3
S
S
S
S
P
+
S
P
S
SH
NH4
HO
P
P
+ 2
OH
2
O
O
OH
S
OH
OH
S-Silyl and S-plumbyl dithiophosphates (Р = 76 and 93 – 100 ppm, respectively) were
prepared by reaction of the corresponding ammonium salt with triethyl chloroplumbane,
triphenyl chloroplumbane, dimethyl dichlorosilane, diphenyl dichloroplumbane, and tetrachloro-
silane in benzene at 80 °C during 2 – 3 h.
R3PbCl
S
R2ECl2
S
_
S
+
O
PS NH4
PS ER2
PSPbR3
O
O
- NH4Cl
2
- 2 NH4Cl
2
2
2
R = Et, Ph
E = Si, R = Me;
E = Pb, R = Ph
SiCl4
- 4 NH4Cl
S
S
_
+
NH4
4
PS
O
PS Si
O
2
2
n
4
Triethyl chloroplumbane and diphenyl dichloroplumbane were also involved in the
reaction with ammonium aryldithiophosphonates in benzene at 80 °C for 2 h to give the
corresponding S-plumbyl dithiophosphonates and bis(aryldithiophosphonato) plumbanes (Р =
100 ppm).
3
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Ph
Ph
S
_
S
Ph2PbCl2
- 2 NH4Cl
S-Pb-S
+
Et3PbCl
- NH4Cl
S
S
O-P
Et3PbS
Ar
NH4 S
P-O
P-O
Ar
Ar
P-O
Ar
Ar = HO
The ammonium dithiophosphates and S-plumbyl dithiophosphonates prepared possess
antimicrobial activity towards Staphylococcus aureus, Escherichia coli and Candida.
ACKNOWLEDGEMENT
The study was performed with financial support of the Russian Foundation for Basic
Researches (Grant No. 11-03-00264-a).
S
NH3
P4S10
S
P
+
4
8
O
P
O
OH
O
O
- 2 H2S
HS
NH4
S
Scheme 1
Ph
+
Ph
H
S
+
S
*
H3N
_
C
*
H3N
C
PS
PSH
O
+
H
O
Me
(S)-(-)-
2
2
Me
(S)-(-)-
Scheme 2
4
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