A synthetic strategy for novel organothiophosphates incorporating a pyridine ring

Article abstract of DOI:10.1080/10426500600634624

Eight novel amidothiophosphates have been successfully achieved using cycloiminium salts of pyridine as the starting material. Phosphorylation was done using phosphorus trichloride, and the resulting functionalized iminohalophosphines in situ were further

Full text of DOI:10.1080/10426500600634624

This article was downloaded by: [University of California, San Diego]
On: 05 June 2015, At: 04:16
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
A Synthetic Strategy for
Novel Organothiophosphates
Incorporating a Pyridine Ring
Vijaya Kabra a , Suneeta Ojha a , Priti Kaushik a &
Arpana Meel a
a Department of Chemistry , University of
Rajasthan , Jaipur, India
Published online: 22 Sep 2006.
To cite this article: Vijaya Kabra , Suneeta Ojha , Priti Kaushik & Arpana Meel (2006)
A Synthetic Strategy for Novel Organothiophosphates Incorporating a Pyridine Ring,
Phosphorus, Sulfur, and Silicon and the Related Elements, 181:10, 2337-2344, DOI:
10.1080/10426500600634624
To link to this article: http://dx.doi.org/10.1080/10426500600634624
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or

indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 181:2337–2344, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600634624
A Synthetic Strategy for Novel Organothiophosphates
Incorporating a Pyridine Ring
Vijaya Kabra
Suneeta Ojha
Priti Kaushik
Arpana Meel
Department of Chemistry, University of Rajasthan, Jaipur, India
Eight novel amidothiophosphates have been successfully achieved using cycloi-
minium salts of pyridine as the starting material. Phosphorylation was done us-
ing phosphorus trichloride, and the resulting functionalized iminohalophosphines
in situ were further oxidized and substituted through sulfur and a suitable sec-
ondary amine (alkyl, alicyclic, and aryl). The reactions were carried out in a dry
nitrogen atmosphere. The synthesized products were characterized using different
1
31
spectroscopic techniques ( H and P NMR). The pyridine nucleus incorporating a
phosphoryl group is highly bioactive. Hence, the synthesized organothiophosphates
should be potential pesticidal molecules.
Keywords Amidothiophosphate; cycloiminium salts; iminohalophosphines
INTRODUCTION
The importance of the phosphoryl group has been reported in the lit-
erature, as it regulates important biological functions of both plants
and animals.1−3 It is conceivable that its attachment to a pyridine nu-
cleus, which itself exhibits a wide spectrum of biological activity,4−8 will
enhance the biological activity of the synthesized product.
In the literature, several synthetic routes for these derivatives have
been reported by different workers.9−12 In our research group, we have
evolved an economical synthetic route where thiazole, benzothiazole,
and pyrimidine nuclei have been incorporated with a thiophosphate
moiety. In this novel synthetic strategy, corresponding cycloiminium
Received November 20, 2005; accepted February 3, 2006.
We are grateful to the head, of the Department of Chemistry, University of Rajasthan,
Jaipur, for providing necessary facilities. We are also highly indebted to the Department
of Chemistry, Punjab University, Chandigarh, for carrying out NMR spectra.
Address correspondence to Vijaya Kabra, University of Rajasthan, Department of
Chemistry, Jaipur 302 004, India. E-mail: sgkabra@sancharnet.in
2337

2338
V. Kabra et al.
salts of these heterocyclic nuclei were phosphorylated with phosphorus
trichloride in the presence of a weak base.13−16 Viewing the importance
of the pyridine nucleus in the proposed work, the similar synthetic
strategy was extended on the cycloiminium salts of pyridine nucleus,
which on phosphorylation achieved the desired title compounds.
RESULTS AND DISCUSSION
Under nitrogen, the N-alkyl-2-aminopyridinium halides (2) have been
reacted with an equimolar amount of phosphorus trichloride and two
equivalents of triethylamine at 0–5◦C in methylene chloride to gener-
ate corresponding iminodichlorophosphines. These intermediates have
been oxidized in situ with elemental sulfur (1/8 equivalents) at an
ambient temperature generating cycloiminylidenamidothiophosphoric
dichlorides (3) in a good yield. These were stable, cream-to-yellow, sharp
melting crystalline solids (Scheme 1).
SCHEME 1
3a–c were subsequently subjected to nucleophilic substitution
with different secondary amines viz. diethylamine, diphenylamine,
and N-methylcyclohexylamine (Scheme 2). Thus, through this syn-
thetic strategy, 8 novel representatives of 2 series of alkylidenamidot-
hiophosphoric esters, namely cycloiminylidenamidothiophosphoric
dichlorides (3a–c) and cycloiminyldenamidobis(dialkyl/diaryl/alkylali-

Novel Organothiophosphates
2339
SCHEME 2
cyclicamido)thiophosphates (4a–c, 5a, and 6c), have been obtained in a
good yield.
All products were crystalline, sharp melting solids; stable under a ni-
trogen atmosphere; and were characterized through elemental analysis
and 1H and 31P NMR techniques. The results have been represented in
Table I.
The N CH2 protons of 3a&c and 4a&c appear as a singlet in the
range δ3.50 to δ5.32 ppm, whereas N CH2 protons of 3b and 4b show a
quartet (3J = 7.1 Hz) at δ4.09–.δ4.27 ppm. The deshielding of the H-6
proton of the pyridine ring is highest as an amino nitrogen is situated
nearby to it. Thus, the H-6 proton appears as an unresolved triplet or
multiplet at δ 7.61–7.82 ppm.
The H-5 proton appears as a doublet of a triplet or a merged triplet
(3 J = 6.0–8.0, 4 J = 1.8 Hz) at δ6.60–6.82 ppm showing vicinal cou-
HH
HH
pling with both the H-4 and H-6 and m-coupling with H-3 protons. A
doublet of doublet is observed for the H-3 proton showing vicinal cou-
pling with H-4 and m-coupling with H-5. The N CH2 protons of the
1
PNCH2CH3 (4a–c) moieties exhibit diastereotopicity; in the H NMR
spectra a doublet of a doublet of a quartet has been observed in 4a–c
due to geminal coupling, coupling with phosphorus, and vicinal cou-
1
pling with adjacent methyl protons. Furthermore, H NMR spectra of
compound 6c exhibited interesting behavior due to the presence of a cy-
clohexyl ring at a nitrogen of an amido moiety, which, as expected, has

2340

2341

2342
V. Kabra et al.
acquired the chair conformation. As reported in the literature17 here
also, the equatorial and axial protons on the same carbon of a locked
6-membered ring forms the AB part of the ABX system. The HA (equa-
torial) protons are relatively deshielded than the HB (axial) protons by
about 0.10 to 0.91 ppm. Five bunches of protons appear as a multiplet
due to geminal (2 J = 10–14 Hz) and vicinal (aX − aX, 3 J = 7.0–9.2)
HH
HH
(ax − ex, 3 J = 2–3 Hz) couplings, respectively.
HH
All physical and spectral details of synthesized products have been
presented in Table I.
EXPERIMENTAL
All solvents and commercial reagents were purified prior to use. The
glasswares, syringes, and needles used in these moisture-sensitive reac-
tions were oven dried at 140◦C. Upon work, solvents were evaporated
under reduced pressure, using a high vacuum. Melting points were
measured by the capillary method on an electric tempo m.p. appara-
tus and are uncorrected. 31P spectra were recorded on Jeol AL 300 at
121.50 MHz (Obset 156 KHz) using 85% H3PO4 as an external stan-
dard, and 1H spectra were recorded on Jeol AL 300 at 300.4 MHz (Obset
130 KHz) using TMS as an internal standard. Elemental analyses were
carried out on Heraeus Carlo Erba 1108 analyzer.
N-Alkyl-2-pyridinylidenamidothiophosphoric dichlorides
(3a–c): General Procedure
To a well-stirred suspension of N-alkyl-2-aminopyridinium halides
(3.0 g, 12.7 mmoles) in methylene chloride (20 mL) at 0–5◦C was added
phosphorus trichloride (1.4 mL, 12.6 mmoles) followed by a dropwise
addition of a solution of triethylamine (3.5 mL, 25.4 mmoles) in methy-
lene chloride (30 ml) under a N2 atmosphere. After 5–6 h of stirring
at r.t. sulfur powder (4.4 g, 12.7 mmoles) was added to it. The result-
ing mixture was left for stirring for 24–30 h after which the solvent
was removed under vacuo and the residue was extracted with ether
(2 × 30 mL). The combined extract was concentrated to 30 mL and kept
in the refrigerator (0◦C), whereupon cream to pale yellow solids sepa-
rated, which were filtered and dried.
N-Alkyl-2-pyridinylidenamidobis(diethylamido)-
thiophosphates (4a–c): General Procedure
A similar procedure that was used for 3a–c was followed, and after
24–30 h of stirring, a solution of diethylamine (4.7 g, 50.8 mmoles) in

Novel Organothiophosphates
2343
methylene chloride was added dropwise at 0–5◦C, and the resulting
mixture was further stirred for 24–30 h. The solvent was removed un-
der vacuo, and the residue was extracted with ether (2 × 30 mL). The
combined etheral extract was concentrated and kept in a refrigerator.
Cream-to-yellow crystals separated out, which were filtered and dried.
In the present procedure, two excess equivalents of diethylamine acted
as base.
N-Alkyl-2-pyridinylidenamido bis(diphenylamido)-
thiophosphates (5a): General Procedure
The previously stated procedure was followed using diphenylamine
(2.2 g, 12.7 mmoles) in place of diethylamine, alongwith the dropwise
addition of a solution of two equivalents of triethylamine (3.5 mL,
25.4 mmoles) in methylene chloride (20 mL) (which was serving as
base). On keeping the concentrated ether extract in refrigerator (0◦C),
white flakes were obtained, which were filtered and dried.
N-Alkyl-2-pyridinylidenamidobis(N-methyl cyclohexylamido)
thiophosphates (6c): General Procedure
The previously stated procedure was followed using N-methyl cyclo-
hexylamine (3.0 mL, 22.6 mmoles) in place of earlier stated amines
with the dropwise addition of a solution of two equivalents of triethy-
lamine (3.5 mL 25.4 mmoles) in methylene chloride (20 mL) (which was
serving as a base). On keeping the concentrated ether extract in a re-
frigerator (0◦C), yellow crystals were obtained, which were filtered and
dried.
CONCLUSION
An economical synthetic route has been developed for the synthesis of
organothiophosphates including a pyridine nucleus. These molecules
are expected to be highly bioactive, and, hence, in our further research
work, bioscreening of these molecules will be done.
REFERENCES
[1] G. Tomlin, Ed., Pesticide Manual, 10th ed. (British Crop Protection Pub. Survey,
London, 1991).
[2] S. P. Singh, S. S. Parmar, K. Raman, and V. I. Stenberg, Chem. Rev., 81, 175 (1981).
[3] G. Danila, Rev. Chem. (Bucharest), 29, 1152 (979); Chem. Abstr., 90, 52037 (1979).
[4] G. J. Atwell, B. F. Cain, and R. N. Seeley, J. Med. Chem., 15, 611 (1972).

2344
V. Kabra et al.
[5] B. F. Cain, G. J. Atwell, and R. N. Seeley, J. Med. Chem., 12, 199 (1969).
[6] A. L. Black and L. A. Summers, J. Chem. Soc., C, 4, 610 (1969).
[7] J. W. McFarland and H. L. Howes, Jr., J. Med. Chem., 12, 1079 (1969).
[8] D. H. Wheeler and J. Gross, J. Amer. Oil Chem. Soc., 42, 924 (1965).
[9] B. A. Arbuzov, V. M. Zoroatrove, and M. P. Osipora, Izv. Akad. Nauk. SSSR, Otdel.
Khim. Nauk, 55, 2163 (1961).
[10] A. P. Marchenko, A. M. Pinchuk, and N. G. Fashchanko, Zh. Obshch. Khim., 43,
1900 (1973).
[11] H. Dorn, H. Graubaum, V. Zeigan, and R. Radeglia, Z. Chem., 15, 485 (1975).
[12] R. M. Kamalov, N. A. Khailova, and M. A. Pudovik, Zh. Obshch. Khim., 64, 1994
(1994).
[13] R. K. Bansal, V. Kabra, R. Munjal, and N. Gupta, Phosphorus, Sulfur, and Silicon,
97, 141 (1994).
[14] V. Kabra, N. Gupta, and R. Mathur, J. Indian. Chem. Soc., 81, 338 (2004).
[15] V. Kabra, N. Gupta, S. Jain, and V. Saxena, Heteroatom Chemistry, 14(6), 498 (2003).
[16] N. Gupta, V. Kabra, V. Saxena, S. Jain, and K. Bhatnagar, Phosphorus, Sulfur, and
Silicon, 178, 851 (2003).
[17] R. M. Silverstein and F. X. Webster, Spectrometric Identification of Organic Com-
pounds, 6th Ed. (John Wiley, New York, 1998).