An easy access to functionalized allyl dithiocarbamates from Baylis-Hillman adducts in water

Article abstract of DOI:10.1016/j.tetlet.2009.01.023

A facile and direct highly stereoselective synthesis of [E]- and [Z]-allyl dithiocarbamates has been accomplished from acetates of Baylis-Hillman (BH) adducts in catalyst-free one-pot three-component coupling reactions of carbon disulfide and amine in wat

Full text of DOI:10.1016/j.tetlet.2009.01.023

Tetrahedron Letters 50 (2009) 1335–1339
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An easy access to functionalized allyl dithiocarbamates from Baylis–Hillman
adducts in water
*
Lal Dhar S Yadav , Rajesh Patel, Vishnu P. Srivastava
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211 002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile and direct highly stereoselective synthesis of [E]- and [Z]-allyl dithiocarbamates has been accom-
plished from acetates of Baylis–Hillman (BH) adducts in catalyst-free one-pot three-component coupling
reactions of carbon disulfide and amine in water under a mild and green procedure with high yields. The
reaction pathway involves the nucleophilic displacement (SN20) of BH acetates by dithiocarbamate
anions. The utility of these allyl dithiocarbamates has also been demonstrated in heterocyclic chemistry.
Ó 2009 Elsevier Science. All rights reserved
Received 27 November 2008
Revised 4 January 2009
Accepted 9 January 2009
Available online 13 January 2009
Keywords:
Ó 2009 Elsevier Ltd. All rights reserved.
Baylis–Hillman adducts
Stereoselective synthesis
Dithiocarbamates
Nucleophilic displacement
1,3-Thiazines
Green procedure
Carbon–sulfur bond formation is a fundamental approach to
introduce sulfur into organic compounds, and this has received
much attention due to its occurrence in many molecules that are
of biological, pharmaceutical, and material interest.1,2 Organic
dithiocarbamates, ubiquitously found in a variety of biologically
active molecules,3 are of high importance in academia as well as
in industry.4 Besides their numerous biological and medicinal
properties including applications in the treatment of cancer,5 they
play pivotal roles in agriculture6 and act as linkers in solid-phase
organic synthesis.7 They are used in the rubber industry as vulca-
nization accelerators,8 in controlled radical polymerization tech-
niques,9, and recently, in the synthesis of ionic liquids.10 Owing
to their strong metal-binding capacity, dithiocarbamates act as
inhibitors of enzymes and have a profound effect on biological sys-
tems. For these reasons, the synthesis of functionalized dithiocar-
bamates with different substitution patterns at the thiol chain
has become a field of increasing interest in synthetic organic chem-
istry during the past few years. Conventional methods involve
reactions of amines with thiophosgene and its derivatives, which
are not desirable for environmental concerns.11 This has led to a re-
cent surge of several one-pot procedures for the synthesis of S-al-
kyl, aryl, and vinyl dithiocarbamates by the reaction of amine with
is rather limited.12d They are used as synthons for the preparation
of various enals,13 which are important features of many natural
products including macrocyclic antibiotics, such as pyrenophorin,
brefeldin, and cytochalasins.14 In addition, S-allyl dithiocarbamates
also serve as versatile intermediates for other synthetic targets,
such as the prostaglandins,15 coriolic and dismorphecolic acids.16
Herein, Baylis–Hillman (BH) chemistry has been applied for the
synthesis of allyl dithiocarbamates (Scheme 1).
The BH reaction17 has become a popular carbon–carbon bond-
forming reaction, which proceeds with a high atom-economic and
yields densely functionalized molecules. They, in turn, provide
opportunities for developing art in organic synthesis via functional
group manipulation, thereby enabling vast applications as versatile
building blocks to generate either bioactive compounds or useful
synthetic intermediates.18 Acetates of BH adducts have been well
established for the synthesis of trisubstituted alkenes and different
multifunctional molecules en route to heterocycles via a nucleo-
philic displacement protocol either in SN2 or in SN20 fashion with
various C-, N-, and O-centred nucleophiles.18a,c,19,20 However, their
utilization for generating sulfur-containing products with S-centred
nucleophiles has been limited and includes only arenesulfinate,21
thiolates22, and thiocyanate anions.23 Until now, the literature
records no report on the synthesis of dithiocarbamates using BH
chemistry.
carbon disulfide and halides, epoxides, or
a,b-unsaturated com-
pounds.12 However, the one-pot synthesis of S-allyl dithiocarba-
mates, synthetic equivalent of b-formyl/halomethyl vinyl anions,
Reactions in aqueous media have attracted much attention in re-
cent times due to environmental acceptability, natural abundance,
and low cost of water. In addition, water often exhibits unique
reactivity and selectivity that cannot be attained in conventional
* Corresponding author. Tel.: +91 5322500652; fax: +91 5322460533.
E-mail address: ldsyadav@hotmail.com (Lal Dhar S Yadav).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.01.023

1336
Lal Dhar S Yadav et al. / Tetrahedron Letters 50 (2009) 1335–1339
R
S
OAc
S
CS2,
NH
S
N
2
S
N
or
CN
water,
rt
6-10 h
EWG
R
COOMe
R
80-94% yields
1
3
4
EWG
= CN, COOMe; R = H, Cl, NO2
Scheme 1. One-pot synthesis of allyl dithiocarbamates 3 and 4 from BH acetates 1.
Table 1
One-pot synthesis of allyl dithiocarbamates 3 and 4 from BH acetates 1 Scheme 1
Entry
BH acetate
Amine 2
Product 3 or 4
Reaction timea (h)
Yieldb,c (%)
OAc
S
3a
7
84
HN
S
N
CN
OAc
CN
S
3b
4a
7.5
80
87
S
N
HN
HN
CN
CN
Cl
Cl
OAc
S
S
9
S
N
COOMe
OAc
COOMe
NO2
4b
6
91
HN
COOMe
O2N
S
N
S
COOMe
OAc
S
3c
8.5
8
85
87
HN
HN
N
CN
OAc
CN
S
3d
S
N
CN
CN
Cl
Cl
OAc
S
4c
9.5
88
HN
S
N
COOMe
OAc
COOMe
NO2
4d
3e
8.5
92
83
HN
S
COOMe
O2N
S
N
S
COOMe
OAc
S
Ph
9
H2N
NH
Ph
CN
CN

Lal Dhar S Yadav et al. / Tetrahedron Letters 50 (2009) 1335–1339
1337
Table 1 (continued)
Entry
BH acetate
Amine 2
Product 3 or 4
Reaction timea (h)
Yieldb,c (%)
OAc
S
Ph
Ph
3f
9
87
S
NH
Ph
H2N
CN
CN
Cl
Cl
OAc
S
S
4e
10
90
94
H2N
S
COOMe
NO2
NH
Ph
COOMe
OAc
Ph
4f
7.5
H2N
COOMe
Ph
O2N
S
NH
COOMe
a
Time for completion of the reaction at rt as indicated by TLC.
Yields of isolated and purified products.
b
c
All compounds gave C, H, and N analyses within 0.37% and satisfactory 1H NMR, 13C NMR, and EIMS data.
organic solvents. Thus, the development of an efficient procedure
for an organic reaction using water as the reaction medium has re-
ceived high priority in the design of a chemical process, and is a
challenging goal of aqueous chemistry.24
is, acrylonitrile-derived BH acetates (1, EWG = CN) afford E-allyl
dithiocarbamates 3 as the sole product while acrylate ester-de-
rived BH acetates (1, EWG = COOMe) exclusively afford [Z]-allyl
dithiocarbamates 4 under the same reaction conditions. The con-
figuration of allyl dithiocarbamates 3 and 4 was assigned on the
basis of the literature precedent,22b,27 1H NMR chemical shift of vi-
nyl protons, and was confirmed by NOE experiments. The products
3 and 4 were studied by NOE experiments. Product 4 showed NOE
between methylene protons and aromatic protons and showed no
NOE between methylene and vinyl protons confirming the Z con-
figuration, and product 3 showed NOE between methylene protons
and vinyl protons confirming the E configuration. Although no
mechanistic studies have been carried out, related stereochemical
reversals are attributed to differences in relative stabilities of tran-
sition states as explained earlier by considering transition state
models.22b,28
Considering the above valid facts and our continued quest for
the development of environmentally friendly alternatives along
with the recent interest in synthetic applications of BH adducts,25
we report herein a one-pot three-component highly stereoselec-
tive synthesis of hitherto unknown trisubstituted [E]- and [Z]-allyl
dithiocarbamates 3 and 4 in water at rt without using a catalyst
(Scheme 1). The present one-pot procedure was performed simply
by stirring a mixture of an amine, CS2, and an acetate of acryloni-
trile/acrylate ester-derived BH adduct in water at rt for 6–10 h to
afford the corresponding allyl dithiocarbamates 3 and 4 in 80–
94% yields and sole diastereoselectivity (Table 1).26 The reaction
pathway involves nucleophilic displacements (SN20) of BH adducts
by dithiocarbamate anions. Significantly, the reaction is highly
stereoselective for both acrylonitrile/acrylate ester-derived BH
acetates, but with reversed stereochemical directive effect, that
Interestingly, the allyl dithiocarbamates 3e, 3f, 4e, and 4f (Table
1) derived from benzyl amine underwent an intramolecular cycliza-
tion reaction in the presence of K2CO3 in methanol upon warming
Table 2
Cyclization of N-benzyldithiocarbamates 3 and 4 into 1,3-thiazines 5
NH
R
NH
N
EWG = CN
Ph
R
N
Ph
S
S
EWG
K2CO3
S
S
R
NH
5a, b
Ph
o
MeOH
,60 C
O
O
S
S
EWG = COOMe
N
3 e, f: EWG = CN
4 e, f: EWG = COOMe
R
R
N
Ph
Ph
S
S
S
S
5c, d
Product
R
Reaction timea (h)
Yieldb (%)
5a
5b
5c
5d
Ph
4-ClC6H4
Ph
4
4
3
3.5
78
81
76
84
4-O2NC6H4
a
Time for completion of the reaction as indicated by TLC.
Yield of isolated and purified products.
b

1338
Lal Dhar S Yadav et al. / Tetrahedron Letters 50 (2009) 1335–1339
the reaction mixture at 60 oC to yield chemically and pharmaceu-
tically interesting entities 3,5-dibenzyl-1,3-thiazines 5a–d (Table
2).29 This illustrates the potential of these allyl dithiocarbamates
in heterocyclic synthesis.
In summary, we have described a one-pot, efficient, and highly
stereoselective green synthetic protocol for hitherto unknown [E]-
and [Z]-allyl dithiocarbamates via the nucleophilic displacement
(SN20) of BH acetates by dithiocarbamate anions in water. This
one-pot protocol avoids the use of bases and toxic organic solvents
by utilizing water, which plays a dual role, as a solvent and pro-
moter. Furthermore, the utility of these allyl dithiocarbamates in
heterocyclic chemistry is demonstrated by their base-catalyzed
intramolecular cyclization into chemically and pharmaceutically
relevant functionalized 1,3-thiazines.
1990, 31, 4155–4158; (e) Chinchilla, R.; Najera, C. Chem. Rev. 2000, 100, 1891–
1928.
14. (a) Bakuzis, P.; Bakuzis, M. L. F.; Weingartner, T. F. Tetrahedron Lett. 1978, 19,
2371–2374; (b)The Total Synthesis of Natural Products; ApSimon, J., Ed.; John
Wiley: New York, 1988; Vol. 8, p 102.
15. (a) Corey, E. J.; Erickson, B. W.; Noyori, R. J. Am. Chem. Soc. 1971, 93, 1724–
1729; (b)Prostaglandin Synthesis; Bindra, J. S., Bindra, R., Eds.; Academic Press:
New York, 1977.
16. de Montarby, L.; Tourbah, H.; Gree, R. Bull. Soc. Chim. Fr. 1989, 126, 419–431.
17. (a) Baylis, A. B.; Hillaman, M. E. D. Offenlegungsschrift 2155113, U.S. Patent
3,743,669, 1972; Chem. Abstr. 1972, 77, 34174.; (b)Organic Reactions; Ciganek,
E., Ed.; Wiley: New York, NY, 1997; Vol. 51, pp 201–305.
18. (a) Singh, V.; Batra, S. Tetrahedron 2008, 64, 4511–4574; (b) Basavaiah, D.; Rao,
K. V.; Reddy, R. J. Chem. Soc. Rev. 2007, 36, 1581–1588; (c) Basavaiah, D.; Rao, A.
J.; Satyanarayana, T. Chem. Rev. 2003, 103, 811–891; (d) Langer, P. Angew.
Chem., Int. Ed. 2000, 39, 3049–3052; (e) Basavaiah, D.; Rao, P. D.; Hyma, R. S.
Tetrahedron 1996, 52, 8001–8062; (f) Basavaiah, D.; Roy, S. Org. Lett. 2008, 10,
1819–1822; (g) Basavaiah, D.; Reddy, K. R.; Kumaragurubaran, N. Nat. Protoc.
2007, 2, 2665–2676.
19. (a) Basavaiah, D.; Reddy, R. J. Org. Biomol. Chem. 2008, 6, 1034–1039; (b) Yadav,
J. S.; Reddy, B. V. S.; Basak, A. K.; Narsaiah, A. V.; Prabhakar, A.; Jagadeesh, B.
Tetrahedron Lett. 2005, 46, 639–641; (c) Shafiq, Z.; Liu, L.; Liu, Z.; Wang, D.;
Chen, Y.-J. Org. Lett. 2007, 9, 2525–2528; (d) Reddy, C. R.; Kiranmai, N.; Babu, G.
S. K.; Sarma, G. D.; Jagadeesh, B.; Chandrasekhar, S. Tetrahedron Lett. 2007, 48,
215–218; (e) Ollevier, T.; Mwene-Mbeja, T. M. Tetrahedron 2008, 64, 5150–
5155.
Acknowledgment
We sincerely thank SAIF, Punjab University, Chandigarh for
providing microanalyses and spectra.
20. (a) Basavaiah, D.; Satyanarayana, T. Tetrahedron Lett. 2002, 43, 4301–4303; (b)
Yadav, J. S.; Gupta, M. K.; Pandey, S. K.; Reddy, B. V. S.; Sarma, A. V. S.
Tetrahedron Lett. 2005, 46, 2761–2763; (c) Li, J.; Wang, X.; Zhang, Y. Tetrahedron
Lett. 2005, 46, 5233–5237; (d) Paira, M.; Mandal, S. K.; Roy, S. C. Tetrahedron
Lett. 2008, 49, 2432–2434.
21. Kabalka, G. W.; Venkataiah, B.; Dong, G. Tetrahedron Lett. 2003, 44, 4673–4675.
22. (a) Liu, Y.; Xu, D.; Xu, Z.; Zhang, Y. Heteroat. Chem. 2008, 19, 188–198; (b) Das,
B.; Chowdhury, N.; Damodar, K.; Banerjee, J. Chem. Pharm. Bull. 2007, 55, 1274–
1276; (c) Cha, M. J.; Song, Y. S.; Lee, K.-J. Bull. Korean Chem. Soc. 2006, 27, 1900–
1902; (d) Kamimura, A.; Morita, R.; Matsuura, K.; Omata, Y.; Shirai, M.
Tetrahedron Lett. 2002, 43, 6189–6191; (e) Binay, P.; Henary, J. C.; Vidal, V.;
Genet, J. P.; Dellis, P. Fr. Demande FR2772027, 1999, 23 p; Chem. Abstr. 1999,
131, 170171.; (f) Deane, P. O.; Guthrie-Strachan, J. J.; Kaye, P. T.; Whittaker, R. E.
Synth. Commun. 1998, 28, 2601–2611.
References and notes
1. Kondo, T.; Mitsudo, T.-A. Chem. Rev. 2000, 100, 3205–3220.
2. (a) Norcross, R. D.; Paterson, I. Chem. Rev. 1995, 95, 2041–2114; (b) Faulkner, D.
J. Nat. Prod. Rep. 1995, 12, 223–269; (c) Liu, G.; Link, J. T.; Pei, Z.; Reilly, E. B.;
Leitza, S.; Nguyen, B.; Marsh, K. C.; Okasinski, G. F.; von Geldern, T. W.; Ormes,
M.; Fowler, K.; Gallatin, M. J. Med. Chem. 2000, 43, 4025–4040; (d) Sawyer, J. S.;
Schmittling, E. A.; Palkowitz, J. A.; Smith, W. J., III J. Org. Chem. 1998, 63, 6338–
6343; (e) Trost, B. M. Chem. Rev. 1978, 78, 363–382; (f) Kita, Y.; Iio, K.;
Kawaguchi, K.-I.; Fukuda, N.; Takeda, Y.; Ueno, H.; Okunaka, R.; Higuchi, K.;
Tsujino, T.; Fujioka, H.; Akai, S. Chem. Eur. J. 2000, 6, 3897–3905.
3. (a) Dhooghe, M.; De Kimpe, N. Tetrahedron 2006, 62, 513–535; (b) Erian, A. W.;
Sherif, S. M. Tetrahedron 1999, 55, 7957–8024.
4. (a) Mukerjee, A. K.; Ashare, R. Chem. Rev. 1991, 91, 1–24; (b) Boas, U.; Gretz, H.;
Christensen, J. B.; Heegaard, P. M. H. Tetrahedron Lett. 2004, 45, 269–272; (c)
Grainger, R. S.; Innocenti, P. Heteroat. Chem. 2007, 18, 568–571; (d) Rudorf, W.-
D. J. Sulfur Chem. 2007, 28, 295–339; (e) Katritzky, A. R.; Singh, S.; Mohapatra, P.
P.; Clemens, N.; Kirichenko, K. ARKIVOK 2005, ix, 63–79.
23. Shrihari, P.; Singh, A. P.; Jain, R.; Yadav, J. S. Synthesis 2006, 2772–2776.
24. (a) Li, C.-J.; Chan, T.-H. In Organic Reactions in Aqueous Media; Wiley: New York,
1997; (b)Organic Synthesis in Water; Grieco, P. A., Ed.; Blackie Academic and
Professional: London, 1998; (c) Lindstrom, U. M. Chem. Rev. 2002, 102, 2751–
2772; (d) Li, C.-J. Chem. Rev. 2005, 105, 3095–3166.
25. (a) Yadav, L. D. S.; Yadav, S.; Rai, V. K. Green Chem. 2006, 8, 455–458; (b) Yadav,
L. D. S.; Yadav, B. S.; Rai, V. K. Synthesis 2006, 1868–1872; (c) Yadav, L. D. S.;
Patel, R.; Rai, V. K.; Srivastava, V. P. Tetrahedron Lett. 2007, 48, 7793–7795; (d)
Yadav, L. D. S.; Rai, V. K. Synlett 2007, 1227–1230; (e) Yadav, L. D. S.; Patel, R.;
Srivastava, V. P. Synlett 2008, 1789–1792; (f) Yadav, L. D. S.; Srivastava, V. P.;
Patel, R. Tetrahedron Lett. 2008, 49, 5652–5654; (g) Yadav, L. D. S.; Awasthi, C.;
Rai, A. Tetrahedron Lett. 2008, 49, 6360–6363.
5. (a) Caldas, E. D.; Conceicào, M. H.; Miranda, M. C. C.; de Souza, L. C. K. R.; Lima,
J. F. J. Agric. Food Chem. 2001, 49, 4521–4525; (b) Bowden, K.; Chana, R. S. J.
Chem. Soc., Perkin Trans. 2 1990, 2163–2166; (c) Ronconi, L.; Marzano, C.;
Zanello, P.; Corsini, M.; Miolo, G.; Macca, C.; Trevisan, A.; Fregona, D. J. Med.
Chem. 2006, 49, 1648–1657; (d) Elgemeie, G. H.; Sayed, S. H. Synthesis 2001,
1747–1771; (e) Goel, A.; Mazur, S. J.; Fattah, R. J.; Hartman, T. L.; Turpin, J. A.;
Huang, M.; Rice, W. G.; Appella, E.; Inman, J. K. Bioorg. Med. Chem. Lett. 2002,
12, 767–770.
6. (a) Chin-Hsien, W. A. N. G. Synthesis 1981, 622; (b) Mizuno, T.; Nishiguchi, I.;
Okushi, T.; Hirashima, T. Tetrahedron Lett. 1991, 32, 6867–6868; (c) Chen, Y. S.;
Schuphan, I.; Casida, J. E. J. Agric. Food Chem. 1979, 27, 709–712; (d) Rafin, C.;
Veignie, E.; Sancholle, M.; Postel, D.; Len, C.; Villa, P.; Ronco, G. J. Agric. Food
Chem. 2000, 48, 5283–5287; (e) Len, C.; Postel, D.; Ronco, G.; Villa, P.; Goubert,
C.; Jeufrault, E.; Mathon, B.; Simon, H. J. Agric. Food Chem. 1997, 45, 3–6.
7. (a) Morf, P.; Raimondi, F.; Nothofer, H.-G.; Schnyder, B.; Yasuda, A.; Wessels, J.
M.; Jung, T. A. Langmuir 2006, 22, 658–663; (b) McClain, A.; Hsieh, Y.-L. J. Appl.
Polym. Sci. 2004, 92, 218–225; (c) Dunn, A. D.; Rudorf, W.-D. Carbon Disulphide
in Organic Chemistry; Ellis Horwood: Chichester, UK, 1989. pp 226–367.
8. (a) Nieuwenhuizen, P. J.; Ehlers, A. W.; Haasnoot, J. G.; Janse, S. R.; Reedijk, J.;
Baerends, E. J. J. Am. Chem. Soc. 1999, 121, 163–168; (b) Thorn, G. D.; Ludwig, R.
A. The Dithiocarbamates and Related Compounds; Elsevier: Amsterdam, 1962.
9. (a) Wood, M. R.; Duncalf, D. J.; Rannard, S. P.; Perrier, S. Org. Lett. 2006, 8, 553–
556; (b) Crich, D.; Quintero, L. Chem. Rev. 1989, 89, 1413–1432; (c) Barton, D. H.
R. Tetrahedron 1992, 48, 2529–2544; (d) Zard, S. Z. Angew. Chem., Int. Ed. 1997,
36, 672–685.
10. Zhang, D.; Chen, J.; Liang, Y.; Zhou, H. Synth. Commun. 2005, 35, 521–526.
11. (a) Tilles, H. J. Am. Chem. Soc. 1959, 81, 714–727; (b) Sugiyama, H. J. Synth. Org.
Chem. Jpn. 1980, 38, 555–563; (c) Walter, W.; Bode, K.-D. Angew. Chem., Int. Ed.
Engl. 1967, 6, 281–293.
12. (a) Azizi, N.; Aryanasab, F.; Torkiyan, L.; Ziyaei, A.; Saidi, M. R. J. Org. Chem.
2006, 71, 3634–3635; (b) Azizi, N.; Pourhasan, B.; Aryanasab, F.; Saidi, M. R.
Synlett 2007, 1239–1242; (c) Azizi, N.; Ebrahimi, F.; Aakbari, E.; Aryanasab, F.;
Saidi, M. R. Synlett 2007, 2797–2800; (d) Azizi, N.; Pourhasan, B.; Aryanasab, F.;
Saidi, M. R. Org. Lett. 2006, 8, 5275–5277; (e) Bhadra, S.; Saha, A.; Ranu, B. C.
Green Chem. 2008, 10, 1224–1230; (f) Ranu, B. C.; Saha, A.; Banerjee, S. Eur. J.
Org. Chem. 2008, 519–523; (g) Liu, Y.; Bao, W. Tetrahedron Lett. 2007, 48, 4785–
4788; (h) Chaturvedi, D.; Mishra, N.; Mishra, V. J. Sulfur Chem. 2007, 28, 39–44;
(i) Chaturvedi, D.; Ray, S. Monatsh. Chem. 2006, 137, 311–317.
26. General procedure for the synthesis of [E]- and [Z]-allyl dithiocarbamates (3) and
(4): A mixture of BH acetate 1 (1 mmol), carbon disulfide (1.2 mmol), and
amine 2 (1 mmol) was vigorously stirred in 1.5 mL of water at rt for 6–10 h
(Table 1). After completion of the reaction (monitored by TLC), the product
was extracted with ether/ethyl acetate (3 ꢀ 10 mL). The combined organic
phase was dried over Na2SO4, filtered, concentrated under reduced pressure,
and purified by silica gel column chromatography (hexane/ethyl acetate 9:1)
to afford the desired products (3) and (4). Physical data for representative
compounds. Compound 3a: Colorless viscous liquid, yield 84%. IR (neat) mmax
2941, 2925, 2854, 2218, 1608, 1480, 1429, 1232, 1210, 1120, 1015, 820, 760,
710 cmꢁ1 1H NMR (400 MHz; CDCl3/TMS) d: 1.71 (br, 6H, piperidine ring),
.
3.76 (s, 2H, CH2S), 3.90 (br, 2H, NCH2), 4.27 (br, 2H, NCH2), 6.91 (s, 1H, PhCH),
7.49–7.68 (m, 5Harom). 13C NMR (100 MHz; CDCl3/TMS) d: 24.7, 25.9, 42.6,
51.8, 52.8, 108.7, 117.1, 128.1, 128.8, 129.5, 135.2, 144.8, 194.7. EIMS (m/z):
302 (M+). Anal. Calcd for C16H18N2S2: C, 63.54; H, 6.00; N, 9.26. Found: C,
63.81; H, 6.22; N, 9.13. Compound 4c: colorless viscous liquid, yield 88%. IR
(neat) mmax 2983, 2920, 2846, 1709, 1610, 1488, 1269, 1205, 1051, 832, 756,
714 cmꢁ1
.
1H NMR (400 MHz; CDCl3/TMS) d: 1.18–1.30 (m, 6H, 2 ꢀ CH3), 3.57
(q, 2H, J = 7.1 Hz, CH2), 3.71 (s, 3H, OMe), 3.89 (q, 2H, J = 7.1 Hz, CH2), 4.03 (s,
2H, CH2S), 7.35–7.48 (m, 5Harom), 7.90 (s, 1H, PhCH). 13C NMR (100 MHz;
CDCl3/TMS) d: 11.8, 13.3, 31.6, 47.3, 50.2, 52.9, 127.0, 128.7, 129.5, 130.2,
135.4, 141.6, 167.2, 191.9. EIMS (m/z): 323 (M+). Anal. Calcd for C16H21NO2S2:
C, 59.41; H, 6.54; N, 4.33. Found: C, 59.78; H, 6.38; N, 4.61. Compound 4e:
colorless viscous liquid, yield 90%. IR (neat)
m
max 3282, 3008, 1711, 1610, 1508,
1482, 1254, 1203. 1091, 1058, 814, 762, 698 cmꢁ1
.
1H NMR (400 MHz; CDCl3/
TMS) d: 3.71 (s, 3H, OMe), 4.06 (s, 2H, CH2S), 4.88 (s, 2H, PhCH2), 7.19–7.31 (m,
4Harom), 7.42–7.53 (m, 6Harom), 7.91 (s, 1H, PhCH), 8.1 (br, NH, exchangeable
with D2O). 13C NMR (100 MHz; CDCl3/TMS) d: 31.4, 51.6, 53.0, 126,8, 127.6,
128.2, 128.8, 129.3, 129.9, 130.7, 135.4, 136.5, 141.4, 167.4, 196.0. EIMS (m/z):
357 (M+). Anal. Calcd for C19H19NO2S2: C, 63.83; H, 5.36; N, 3.92. Found: C,
63.60; H, 5.25; N, 3.55.
13. (a) Hayashi, T. Tetrahedron Lett. 1974, 15, 339–342; (b) Nakai, T.; Shiono, H.;
Okawara, M. Tetrahedron Lett. 1974, 15, 3625–3628; (c) Nakai, T.; Shiono, H.;
Okawara, M. Chem. Lett. 1975, 4, 249–252; (d) Hayashi, T. Tetrahedron Lett.
27. (a) Basavaiah, D.; Sarma, P. K. S.; Bhavani, A. K. D. J. Chem. Soc., Chem. Commun.
1994, 1091–1092; (b) Minami, I.; Yuhara, M.; Shimizu, I.; Tsuji, J. J. Chem. Soc.,
Chem. Commun. 1986, 118–119.

Lal Dhar S Yadav et al. / Tetrahedron Letters 50 (2009) 1335–1339
1339
28. (a) Buchholz, R.; Hoffmann, H. M. R. Helv. Chim. Acta 1991, 74, 1213–1220; (b)
Das, B.; Banerjee, J.; Ravindranath, N. Tetrahedron 2004, 60, 8357–8361.
29. General procedure for the synthesis of 3,5-dibenzyl-1,3-thiazines (5): A solution of
allyl dithiocarbamates 3e,f or 4e,f (1 mmol) and anhydrous K2CO3 (1.2 mmol)
in 4 mL methanol was heated at 60 oC for 3–4 h with stirring (Table 2). The
reaction progress was monitored by TLC. Upon completion, the reaction
mixture was cooled to rt, and methanol was removed under reduced pressure.
The residue thus obtained was treated with water (20 mL) and extracted with
ethyl acetate (3 ꢀ 15 mL). The combined organic phase was dried over Na2SO4,
filtered, and evaporated under reduced pressure. The resulting crude product
was purified by silica gel column chromatography using hexane/ethyl acetate
(8.5:1.5) as an eluent to give the pure product 5. Physical data for
representative compound. Compound 5a: yellowish viscous liquid, yield 78%.
a
IR (neat) m .
max 3309, 3010, 2971, 2810, 1610, 1580, 1450, 1090, 764, 710 cmꢁ1
1H NMR (400 MHz; CDCl3/TMS) d: 3.73 (s, 2H, PhCH2), 4.68 (s, 2H, PhCH2 N),
5.81 (br, 1H, NH, exchangeable with D2O), 6.80 (s, 1H, CHS), 7.21–7.69 (m,
10Harom). 13C NMR (100 MHz; CDCl3/TMS) d: 31.5, 51.8, 112.7, 126.0, 127.1,
127.9, 128.7, 129.8, 135.5, 136.6, 138.1, 157.2, 192.1. EIMS (m/z): 324 (M+).
Anal. Calcd for C18H16N2S2: C, 66.63; H, 4.97; N, 8.63. Found: C, 66.97; H, 4.74;
N, 8.46.