An efficient one pot synthesis of carbamate esters through alcoholic tosylates

Article abstract of DOI:10.1081/SCC-120006028

An efficient O-alkylation of alcoholic tosylates with amines in a K₂CO₃/CO₂ system in the presence of tetrabutyl ammonium iodide (TBAI) provides exclusive formation of carbamates.

Full text of DOI:10.1081/SCC-120006028

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AN EFFICIENT ONE POT SYNTHESIS OF CARBAMATE
ESTERS THROUGH ALCOHOLIC TOSYLATES*
Devdutt Chaturvedi a , Atul Kumar a & S. Ray b
a Medicinal Chemistry Division, Central Drug Research Institute, Lucknow, 226 001, India
b Medicinal Chemistry Division, Central Drug Research Institute, Lucknow, 226 001, India
Published online: 20 Aug 2006.
To cite this article: Devdutt Chaturvedi , Atul Kumar & S. Ray (2002) AN EFFICIENT ONE POT SYNTHESIS OF CARBAMATE
ESTERS THROUGH ALCOHOLIC TOSYLATES*, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 32:17, 2651-2655, DOI: 10.1081/SCC-120006028
To link to this article: http://dx.doi.org/10.1081/SCC-120006028
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 17, pp. 2651–2655, 2002
AN EFFICIENT ONE POT SYNTHESIS OF
CARBAMATE ESTERS THROUGH
ALCOHOLIC TOSYLATES*
Devdutt Chaturvedi, Atul Kumar, and S. Rayy
Medicinal Chemistry Division, Central Drug Research
Institute, Lucknow 226 001, India
ABSTRACT
An efficient O-alkylation of alcoholic tosylates with amines in
a K2CO3/CO2 system in the presence of tetrabutyl ammonium
iodide (TBAI) provides exclusive formation of carbamates.
Key Words: O-Alkylation of tosylates; Tetrabutylammonium-
iodide (TBAI); Carbamates
Organic carbamates represent an important class of compounds
having various properties. They have largely found use as agrochemicals[1]
(pesticides, fungicides, herbicides), pharmaceuticals,[2] as intermediates in
organic synthesis,[3] protecting groups in peptide synthesis[4] and as linkers
in combinatorial chemistry.[5] Hence considerable interest has generated in
the recent past for development of an effecient and safe methodology for
carbamate synthesis. Classical syntheses of carbamates involve direct alco-
holysis of phosgene or its derivatives,[6] aminolysis of chloroformates[7] and
*CDRI-Communication no: 6143.
yCorresponding author. E-mail: sraycdri@yahoo.com
2651
DOI: 10.1081/SCC-120006028
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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2652
CHATURVEDI, KUMAR, AND RAY
alcoholysis of isocyanates,[8] thus utilizing phosgene, a harmful chemical,
directly or indirectly.
Recently carbondioxide, a cheap and safe reagent, has been tapped as
an alternative to phosgene for the introduction of a CO group. Preparation
of carbamates has been reported using CO2 electrochemically,[9] super cri-
tically[10] and in combination of metal and non-metal species.[11] CO2 alone
has low reactivity with nucleophiles. With amines it gives unstable carbamic
acid (1). However, with 2 molar equivalence of amine, monoalkylammo-
nium alkyl carbamate ion (2) is formed.
þ À
ð2Þ
RNHCOOH: ½RNH3Š
½OOCNHRŠ
ð1Þ
The alkylammonium carbamate thus formed reacts with alkyl halide
to give rise to N- or O-alkylation (carbamate) products. Formation of
O-alkylation product has been reported in the reaction of primary or
secondary amines, CO2 and alkyl halides in the presence of strong proton
acceptors e.g., DBU,[12] transition metal complexes and crown ether.[13]
It was observed,[14,15,16] that presence of a phase transfer catalyst in the
alkylation of secondary amines with various alkyl halides led to the forma-
tion of carbamates.
Based on the concept of formation of the ionic species 2, we investigated
the carbamate synthesis from alcoholic tosylates. The carbonium ion gener-
ated from the tosyl esters would undergo nucleophilic attack by 2 leading to
the formation of carbamate esters (Scheme 1). Thus, tosyl ester of an alcohol
which is easily synthesized[17] by reacting alcohol with p-toluene sulphonyl
chloride was used as a substrate for the preparation of carbamates. Different
alcoholic tosylates were reacted with the aliphatic/aromatic amines in
dry DMSO in the presence of CO2/K2CO3 and a phase transfer catalyst,
Scheme 1.

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CARBAMATE ESTERS
2653
Table 1.
Entry No.
R
R1
R2
Time (h)
Yields %
1
2
3
4
5
6
7
8
9
10
n-C3H7
C8H17
C8H17
C4H9
Cyclohexyl
C3H7
3-MePhCH2
C6H13
C4H9
C6H13
C3H7
H
H
H
H
H
H
H
H
5–6
5–6
5–6
5–6
5–6
5–6
5–6
5–6
5–6
5–6
90.5
73.16
75.1
88.25
72.26
90.03
82.60
88.65
80.06
71.13
(H3C)2 ꢁ CH ꢁ CH2
H3C(CH2)3
H3C(CH2)4
H3C(CH2)4
H3C(CH2)6
H3C(CH2)8
PhCH2
PhCH2CH2
PhCH2
H
C3H7
tetrabutyl ammonium iodide, to furnish desired carbamate esters in high
yields. The order of yield of carbamates formed from amines was found to
be as follows: RNH2>R2NH>Ar-NH2. In the case of aromatic amines, use
of benzyl triethyl ammonium hydroxide (Triton B) as phase transfer catalyst
and dry HMPAas a solvent gave better results. The yields of various carba-
mates prepared by using different amines and alcoholic tosylates is given in
the Table 1.
TYPICAL METHOD OF PREPARATION
n-Butyl n-octylcarbamate (1): Amixture of anhydrous K CO3 (5 gm),
2
dry DMSO (30 mL), n-octylamine (0.72 mL, 4 mmole), was taken in a 50 mL
two neck flask. The temperature of the reaction was maintained at 90–100ꢀC
and purified CO2 gas was bubbled through it. Reaction was continued for
1 h, tetrabutylammonium iodide (0.20 gm, 5 mmole) was added to it.
The reaction was further continued for 1/2 h, n-butyltosyl ester (0.5 gm,
2.19 mmole) was added to it and reaction continued for another 3–4 h.
The completion of the reaction was checked by TLC. Reaction mixture
was poured in to distilled water (50 mL) and extracted with ethylacetate
thrice. The organic layer was dried over anhydrous Na2SO4 and concen-
trated to get pure oily compound (Yield 0.43 gm, 90.52%, oil)
IR ¼ 1787 cmÀ1 (O-CO-NH). 1H NMR (CDCl3) ꢀ ¼ 0.77–0.87 (t, 6H,
CH3), 0.89–0.99 (m, 4H, CH2), 1.02–1.21 (m, 4H, CH2), 1.25–1.34
(m, 4H, CH2), 1.35–1.39 (m, 2H, CH2), 1.52–1.54 (m, 2H, CH2),
3.87–3.92 (t, 2H, CH2), 4.02–4.06 (t, 2H, CH2O), 4.67–4.71 (bs, H, NH).

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2654
CHATURVEDI, KUMAR, AND RAY
Isoamyl n-Octylcarbamate (2): IR (Neat) ¼ 1702 cmÀ1 (-O-CO-NH).
1H NMR (CDCl3) ꢀ ¼ 0.67–0.75 (d, 6H, CH3), 0.85–0.93 (t, 3H, CH3),
0.95–1.34 (m, 12H, CH2), 1.35–1.37 (m, H, CH), 1.7–1.9 (m, 2H, CH2),
4.02–4.04 (t, 2H, CH2), 4.73–4.75 (bs, H, NH). (Yield 0.36 g, oil).
n-Pentyl n-butylcarbamate (3): IR (Neat) ¼ 1789 cmÀ1 (O-CO-NH).
1H NMR (CDCl3) ꢀ ¼ 0.87–0.95 (t, 6H, CH3), 1.02–1.66 (m, 12H, CH2),
4.05–4.21 (t, 2H, OCH2), 4.65–4.73 (bs, H, NH), (Yield, 0.29 g, oil).
n-Hexyl cyclohexylcarbamate (4): IR (KBr) ¼ 1698 cmÀ1 (O-CO-NH),
1H NMR (CDCl3) ꢀ ¼ 0.85–0.91 (t, 3H, CH3), 0.95–1.71 (m, 6H, CH2),
4.02–4.06 (t, 2H, CH2-O), 4.75–4.78 (bs, H, NH), 1.99–2.10 (m, 10H, cyclo-
hexyl-CH2), 1.91–2.1 (m, CH of cyclohexyl ring) (Yield 0.43 g, m.p.
139–140ꢀC).
n-Hexyl n-propylcarbamate (5): IR (Neat) ¼ 1693 cmÀ1 (O-CO-NH),
1H NMR (CDCl3) ꢀ ¼ 0.85–0.93 (m, 3H, CH3), 1.22–1.66 (m, 12H, CH2),
2.3–2.7 (s, 2H, CH2), 3.7–3.7 (s, 3H, OCH3), 4.73–4.77 (bs, H, NH),
7.12–7.77 (m, 4H, Ar-H) (Yield, 0.26 g, oil).
n-Octyl m-methoxybenzylcarbamate (6): IR (KBr) ¼ 1705 cmÀ1
1
(O-CO-NH) H NMR (CDCl3) ꢀ ¼ 0.87–0.93 (t, 6H, CH3), 1.02–1.77 (m,
10H, CH2), 3.22–3.55 (m, 2H, CH2-NH), 4.05–4.12 (t, 2H, CH2) (Yield
0.45 g, m.p. 137ꢀC).
n-Decyl n-hexylcarbamate (7): IR (Neat): 1693 cmÀ1.1H NMR (CDCl3)
ꢀ ¼ 0.89–0.93 (m, 12H, CH2), 1.55–1.67 (m, 8H, CH2), 2.96–2.99 (t, 2H,
CH2), 4.10–4.32 (t, 2H, CH2-O), (Yield 0.38 g, oil).
2-Phenylethyl n-butylcarbamate (8):[18] IR(neat): 1692 cmÀ1 (O-CO-NH).
1H NMR (CDCl3) ꢀ ¼ 0.87–0.94 (3H, m, CH3), 1.25–1.35 (2H, m, CH2),
1.38–1.44 (2H, m, CH2), 2.13–2.20 (2H, m, CH2NH), 2.3–2.7 (2H, m,
CH2Ar), 3.5–3.8 (2H, t, CH2O), 7.12–7.77 (5H, m, Ar-H) (Yield 0.37 g, oil).
3-Phenylpropyl n-hexylcarbamate (9): IR (Neat) ¼ 1697 cmÀ1 (O-CO-
1
NH). H NMR (CDCl3) ꢀ ¼ 0.92–0.97 (t, 3H, CH3), 1.29–1.32 (m, 10H,
CH2), 2.93–2.85 (t, 2H, CH2-N), 2.87–2.95 (t, 2H, CH2-Ar), 4.22–4.32
(t, 2H, CH2), 7.12–7.77 (m, 5H, Ar-H) (Yield 0.38 g, oil).
2-Phenylethyl di-isopropylcarbamate (10): IR (Neat) ¼ 1695 cmÀ1 (-O-
1
CO-NH). H NMR (CDCl3) ꢀ ¼ 0.89–0.94 (t, 6H, CH3), 1.23–1.44 (m, 8H,
CH2), 2.83–2.86 (t, 4H, CH2), 2.87–2.95 (t, 2H, CH2-Ar), 4.21–4.32 (t, 2H,
CH2-O), 7.13–7.77 (m, 5H, Ar-H) (Yield, 0.38 g, oil).
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CARBAMATE ESTERS
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Received in the Netherlands September 2, 2001

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