Solvent-free synthesis of 2H-pyrans: One-pot reactions of dithiocarbamates, alkyl propiolates, and isocyanides

Article abstract of DOI:10.1002/jhet.809

A novel, convenient, and an efficient approach to the synthesis of 2H-pyrans has been reported based on the multicomponent reaction. Solvent-free condition for the reaction of dithiocarbamates, alkyl propiolates and isocyanides lead to the formation of 2H-pyrans in good yields. In these reactions, synthesis of 2H-pyrans is possible based on the one-pot reaction and without using any catalyst. The mild reaction conditions and high yields of the products exhibit the good synthetic advantage of these methods. Copyright

Full text of DOI:10.1002/jhet.809

402
Solvent-Free Synthesis of 2H-Pyrans: One-Pot Reactions of
Dithiocarbamates, Alkyl Propiolates, and Isocyanides
Vol 49
Zinatossadat Hossaini,a* Faramarz Rostami-Charatib,b Rahimeh Hajinasiria,a
Hojatollah Jafaryanc,c and Mehdi Shahrakidd
aDepartment of Chemistry, Islamic Azad University, Qaemshahr Branch, Mazandaran, Iran
bDepartment of Chemistry, Faculty of Science, Gonbad Kavous University, P.O.Box 163, Gonbad, Iran
cDepartment of Fishery, Gonbad University of Agricultural Sciences and Natural Resources,
Gonbad, Iran
dDepartment of Chemistry, Islamic Azad University, Zahedan Branch, Zahedan, Iran
*E-mail: zshossaini@yahoo.com
Received November 7, 2010
DOI 10.1002/jhet.809
Published online 10 November 2011 in Wiley Online Library (wileyonlinelibrary.com).
A novel, convenient, and an efficient approach to the synthesis of 2H-pyrans has been reported based
on the multicomponent reaction. Solvent-free condition for the reaction of dithiocarbamates, alkyl pro-
piolates and isocyanides lead to the formation of 2H-pyrans in good yields. In these reactions, synthesis
of 2H-pyrans is possible based on the one-pot reaction and without using any catalyst. The mild reac-
tion conditions and high yields of the products exhibit the good synthetic advantage of these methods.
J. Heterocyclic Chem., 49, 402 (2012).
INTRODUCTION
addition reaction under solvent-free conditions at 50ꢀC to
produce 2H-pyran derivatives 4 in 87–92% yields
(Scheme 1). Structures of compounds 4a–4f were deduced
from their IR, 1H NMR, and 13C NMR spectra. The mass
spectra of these compounds displayed molecular ion
peaks at the appropriate m/z values. The 1H NMR spec-
trum of 4a exhibited a triplet at d ¼ 1.31 (3J ¼ 7.5 Hz)
for the methyl group and four singlets for the tert-butyl
(d 1.25 ppm), methoxy (d 3.78 ppm), and olefinic (d 6.57
and 6.64 ppm) protons. The proton decoupled 13C NMR
spectrum of 4a showed 12 distinct resonances in agree-
ment with the proposed structure. Two single resonances
at d ¼ 161.2 and 162.3 ppm are observed in the 13C
NMR spectrum of 4a, which are attributed to the carbonyl
groups. Although we have not established the mechanism
of the reactions in an experimental manner, a possible ex-
planation is proposed in Scheme 2. Dithiocarbamates 1
were produced from the reaction of secondary amines,
carbon disulfide, and alkyl bromides under solvent-free
conditions. On the basis of the well-established chemistry
of isocyanides [12–17], it is reasonable to assume that the
compound 5 apparently results from initial addition of the
isocyanide to the alkyl propiolates that adds to dithiocar-
bamate 1 resulting in the formation of 6, which undergoes
cyclization to generate the 2H-pyrans 4a–f.
The methods of green chemistry continue to grow in im-
portance. Alternate processes help to conserve resources
and can even reduce costs. The replacement of convention
solvents with water or solvent-free conditions, which is
harmless to health and is available in large quantities, is
one of the most interesting basic approaches along these
lines. Multicomponent reactions (MCRs) have been gener-
ally used by synthetic chemists as a basic means to gener-
ate molecular diversity from bifunctional substrates that
react repeatedly in an intramolecular method [1–4]. Devis-
ing such types of MCRs that inclusive the formation of
multiple bonds in a single action is one of the main chal-
lenges in new organic synthesis [5–9]. They afford a great
tool toward the one pot synthesis of various and complex
compounds as well as small and drug-like heterocycles
[10]. MCRs that involve isocyanides are by far the most
flexible reactions in terms of scaffolds and number of
handy compounds [1–5,11]. Here, we describe an efficient
synthesis of 2H-pyran derivatives via the reaction of a
dithiocarbamates, alkyl propiolates and isocyanides under
solvent-free conditions at 50ꢀC (Scheme 1).
RESULT AND DISCUSSION
In conclusion, we have developed the most useful and
dependable procedure currently available for the synthe-
sis of 2H-pyrans by using low cost and readily available
As indicated in Scheme 1, dithiocarbamates 1, alkyl
propiolates 2, and isocyanides 3 undergo a smooth 1:1:1
C
V
2011 HeteroCorporation

March 2012
Solvent-Free Synthesis of 2H-Pyrans: One-Pot Reactions of Dithiocarbamates,
Alkyl Propiolates, and Isocyanides
403
Scheme 1
(CAN), 63.2 (CH2O), 118.4 (CH), 119.5 (CH), 135.2 (C),
143.7 (C), 148.6 (C¼¼N), 161.2 (C¼¼O), 162.3 (C¼¼O) ppm.
Methyl 2-(tert-butylimino)-6-(4-methylpheny)l-2H-pyran-
4-carboxylate (4b). Yellow powder, mp 138–140ꢀC, yield:
0.54 g (90%). IR (KBr) (mmax/cmꢁ1): 1732, 1687, 1567, 1525
and 1248 cmꢁ1. 1H NMR: d ¼ 1.27 (9 H, s, CMe3), 2.36 (3
H, s, Me), 3.76 (3 H, s, MeO), 6.67 (1 H, s, CH), 6.92 (1 H, s,
CH), 7.45 (2 H, d, 3J ¼ 7.5 Hz, 2 CH), 7.82 (2 H, d, 3J ¼ 7.5
Hz, 2 CH) ppm. 13C NMR: d ¼ 21.6 (Me), 31.0 (CMe3),
51.7 (MeO), 57.4 (CAN), 108.6 (CH), 112.4 (CH), 125.5 (2
CH), 129.6 (2 CH), 133.4 (C), 134.2 (C), 137.3 (C), 155.5
(C¼¼N), 156.3 (C), 164.2 (C¼¼O) ppm.
starting materials in one-pot. This method represents a
simple and green procedure, uses mild reaction condi-
tions, and has general applicability. It avoids hazardous
organic solvents and toxic catalysts and gives nearly
quantitative yields without any byproducts in most
cases.
EXPERIMENTAL
All chemicals were obtained from commercial sources.
Melting points were measured on a Kofler hot stage apparatus
and are uncorrected. 1H NMR and 13C NMR spectra were
obtained with a Bruker FT-500 spectrometer in chloroform-d1,
and tetramethylsilane was used as an internal standard. Mass
spectra were recorded with a Finnigan Mat TSQ-70 spectrome-
ter. Infrared (IR) spectra were acquired on a Nicollet Magna
550-FT spectrometer. Elemental analyses were carried out
with a Perkin-Elmer model 240-C apparatus. The results of
elemental analyses (C, H, N) were within 60.4% of the calcu-
lated values.
Typical procedure for the preparation of 2H-pyran
derivatives 4. A mixture of dithiocarbamates (2 mmol) and
alkyl propiolates (2 mmol) was warmed at about 50ꢀC for 2 h.
Then, the isocyanide (2 mmol) was added slowly. The reaction
mixture was stirred for 8 h at room temperature, and then
poured into water (15 mL). The resulting precipitate was sepa-
rated by filtration and was purified from diethyl ether (Et2O)
to afford the pure title compounds.
Eethyl 2-(tert-butylimino)-6-(4-nitropheny)l-2H-pyran-4-
carboxylate (4c). Pale yellow powder, mp 138–140ꢀC, yield:
0.60g (87%). IR (KBr) (mmax/cmꢁ1): 1730, 1687, 1645, 1545
and 1257 cmꢁ1. 1H NMR: d ¼ 1.29 (9 H, s, CMe3), 1.30 (3
H, t, 3J ¼ 7.3 Hz, Me), 4.10 (2 H, q, 3J ¼ 7.3 Hz, CH2O),
6.58 (1 H, s, CH), 6.86 (1 H, s, CH), 8.12 (2 H, d, 3J ¼ 8.2
Hz, 2 CH), 8.35 (2 H, d, 3J ¼ 8.2 Hz, 2 CH) ppm. 13C NMR:
d ¼ 14.2 (Me), 30.5 (CMe3), 58.2 (CAN), 61.4 (CH2O),
108.7 (CH), 121.4 (CH), 126.5 (2 CH), 130.7 (2 CH), 138.5
(C), 141.6 (C), 147.6 (C), 158.4 (C), 159.2 (C¼¼N), 162.4
(C¼¼O) ppm. Anal. Calc. for C18H20N2O7 (344.36): C,
62.78; H, 5.85; N, 8.13 found: C, 62.65; H, 5.76; N, 8.04%.
Ethyl 2-(cyclohexylimino)-6-(4-nitropheny)l-2H-pyran-4-
carboxylate (4d). Yellow powder, mp 142–144ꢀC, yield: 0.85
g (894%). IR (KBr) (mmax/cmꢁ1): 1728, 1695, 1663, 1554 and
1232 cmꢁ1. 1H NMR: d ¼ 1.28 (3 H, t, 3J ¼ 7.4 Hz, Me),
1.32 (2 H, m, CH2), 1.38 (2 H, m, CH2), 1.45 (2 H, m, CH2),
1.65 (2 H, m, CH2), 1.83 (2 H, m, CH2), 3.76 (1 H, m,
N-CH), 4.24 (2 H, q, 3J ¼ 7.4 Hz, CH2O), 6.52 (1 H, s, CH),
6.74 (1 H, s, CH), 7.72 (2 H, d, 3J ¼ 7.6 Hz, 2 CH), 7.87 (2
H, d, 3J ¼ 7.6 Hz, 2 CH) ppm. 13C NMR: d ¼ 14.2 (Me),
24.5 (CH2), 24.7 (CH2), 25.8 (CH2), 34.3 (CH2), 35.0 (CH2),
57.0 (CAN), 61.8 (CH2O), 108.3 (CH), 118.4 (CH), 126.2
(2 CH), 130.7 (2 CH), 136.2 (C), 142.5 (C), 148.6 (C), 154.0
(C¼¼N), 159.7 (C), 162.8 (C¼¼O) ppm. Anal. Calc. for
6-Ethyl 4-methyl-2-(tert-butylimino)-2H-pyran-4,6-dicar-
boxylate (4a). Pale yellow powder, mp 118–120ꢀC, yield:
0.52 g (92%). IR (KBr) (mmax/cmꢁ1): 1730, 1728, 1587, 1524
and 1224 cmꢁ1. 1H NMR: d ¼ 1.25 (9 H, s, Me3C), 1.31
(3 H, t, 3J ¼ 7.5 Hz, Me), 3.78 (3 H, s, MeO), 4.34 (2 H, q, 3J
¼ 7.5 Hz, CH2O), 6.57 (1 H, s, CH), 6.64 (1 H, s, CH) ppm.
13C NMR: d ¼ 14.1 (Me), 29.5 (Me3C), 52.4 (MeO), 55.5
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

404
Z. Hossaini, F. Rostami-Charatib, R. Hajinasiria, H. Jafaryanc, and M. Shahrakid
Vol 49
C20H22N2O5 (370.39): C, 64.85; H, 5.99; N, 7.56 found: C,
64.76; H, 5.84; N, 7.46%.
Acknowledgment. It would be acknowledged that this work was
financial supported by the Nation Elite Foundation.
6-Ethyl
4-methyl-2-(1,1,3,3-tetramethylbutylimino)-2H-
pyran-4,6-tricarboxylate (4e). Pale yellow powder, mp 132–
134ꢀC, yield: 0.62 g (92%). IR (KBr) (mmax/cmꢁ1): 1725,
1720, 1685, 1584, 1423 and 1257 cmꢁ1. 1H NMR: d ¼ 1.12
(9 H, s, CMe3), 1.24 (3 H, t, 3J ¼ 7.5 Hz, Me), 1.52 (3 H, s,
Me), 1.55 (3 H, s, Me), 1.84 (2 H, s, CH2), 3.78 (3 H, s,
MeO), 4.20 (2 H, q, 3J ¼ 7.5 Hz, Me), 6.84 (1 H, s, CH),
6.92 (1 H, s, CH) ppm. 13C NMR: d ¼ 14.0 (Me), 29.5 (C),
30.2 (Me), 31.8 (CMe3), 32.3 (Me), 51.5 (MeO), 55.6 (CH2),
59.2 (CAN), 61.5 (CH2O), 109.4 (CH), 116.8 (CH), 133.5
(C), 144.5 (C), 158.6 (C), 161.5 (C¼¼O), 163.5 (C¼¼O) ppm.
Anal. Calc. for C18H27NO5 (337.41): C, 64.08; H, 8.07; N,
4.15 found: C, 63.94; H, 7.96; N, 4.02%.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet