An efficient one-pot synthesis of carbazates and dithiocarbazates through the corresponding alcohols using Mitsunobu's reagent

Article abstract of DOI:10.1007/BF03249073

A novel Mitsunobu-based protocol has been developed for the synthesis of carbazates and dithiocarbazates through the variety of corresponding primary, secondary and tertiary alcohols and various kinds of substituted hydrazines using Mitsunobu's reagent an

Full text of DOI:10.1007/BF03249073

J. Iran. Chem. Soc., Vol. 8, No. 2, June 2011, pp. 396-400.
JOURNAL OF THE
Iranian
Chemical Society
An Efficient One-Pot Synthesis of Carbazates and Dithiocarbazates through the
Corresponding Alcohols Using Mitsunobu’s Reagent
†
A.K. Chaturvedia, D. Chaturvedib, ,*, N. Mishraa and V. Mishraa
aSynthetic Research Laboratory, Department of Chemistry, B. S. A. P. G. College, Mathura-281004, U. P., India
bBio-Organic Chemistry Division, Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi-180001, J. & K.,
India
†Present address for correspondence: Natural Products Chemistry Division, North-East Institute of Science and
Technology (CSIR), Jorhat-785006, Assam, India
(Received 16 November 2009, Accepted 29 January 2010)
A novel Mitsunobu-based protocol has been developed for the synthesis of carbazates and dithiocarbazates through the variety
of corresponding primary, secondary and tertiary alcohols and various kinds of substituted hydrazines using Mitsunobu’s reagent
and CO2/CS2 system, in good to excellent yields.
Keywords: Alcohols, Carbon dioxide, Carbon Disulfide, Mitsunobu’s reagent, Carbazates, Dithiocarbazates
INTRODUCTION
CO2/CS2. Moreover, their formation using CO2/CS2 employed
harsh reaction conditions such as use of strong bases, higher
reaction temperatures and longer reaction times [10]. Thus, we
were prompted to embark on developing the improved
procedures. Our group [11] has been engaged over the past
several years in the development of new methodologies for the
preparation of carbamates, dithiocarbamates, and related
compounds using cheap, abundantly available, and safe
reagents like CO2 and CS2, respectively.
Recently, we reported [12] the synthesis of carbamates,
dithiocarbamates, carbonates, O,S-dialkyl dithiocarbonates
(xanthates), S-alkyl thiocarbamates, trithiocarbonates and S,S-
dialkyl carbonates, through the variety of starting materials
Organic carbazates and dithiocarbazates constitute an
important and versatile class of compounds for a variety of
industrial, synthetic and medicinal applications [1]. They have
been extensively used as pharmaceuticals [2], agrochemicals
[3], intermediates in organic synthesis [4], for the protection of
amino groups in peptide synthesis [5] and linkers in solid
phase organic synthesis [6] and as donor ligands in
complexation reactions with transition metals [7]. These uses
necessitate their preparation through a convenient and safe
methodology.
To satisfy demand, their synthesis has been changed from
the use of costly and toxic chemicals like phosgene/
thiophosgene [8] and its derivatives [9] directly or indirectly, to
the abundantly available cheap and safe reagents such as
using Mitsunobu’s reagent. We report herein
a
chemoselective, highly efficient and mild synthesis of
carbazates and dithiocarbazates from the corresponding
variety of primary, secondary and tertiary alcohols and
substituted hydrazines using Mitsunobu’s reagent/CO2 and
*
Corresponding author. E-mail: devduttchaturvedi@gmail.com

Chaturvedi et al.
triphenylphosphine (7.56 mmol) and diethyl azodicarboxylate
Mitsunobu’s reagent/CS2 system, respectively.
(7.56 mmol) was added slowly in 2-3 small portions. Next,
corresponding alcohol (7.56 mmol) was added in it with
constant stirring at rt. The reaction was continued until
completion (cf Table 2) as confirmed by TLC. The reaction
mixture was then poured into distilled water (50 ml) and
extracted with ethyl acetate thrice. The organic layer was
separated and dried over anhydrous sodium sulphate and then
concentrated to afford the desired dithiocarbazate compound.
N’-(4-Methoxyphenyl) hydrazine carbodithioc acid
butyl ester (Table 2, entry 1, C12H18N2OS2). IR υ (neat) =
EXPERIMENTAL
Chemicals were procured from Merck, Aldrich and Fluka
chemical companies. Reactions were carried out under Argon.
IR spectra 4000-200 cm-1 were recorded on Bomem MB-104-
FTIR spectrophotometer using neat technique, whereas NMRs
were scanned on an AC-300F, NMR (300 MHz), instrument
using CDCl3 and TMS as internal standard. Elemental analysis
were conducted by means of a Carlo-Erba EA 1110-CNNO-S
analyzer and agreed favorably with calculated values.
1
675, 1210 cm-1; H NMR (300 MHz, CDCl3) δ = 0.85 (t, 3H,
J = 7.2 Hz, CH3), 1.33 (m, 2H, CH2CH3 ), 1.85 (m, 2H,
CH3CH2CH2), 2.0 (s, NH), 2.95 (t, 2H, J = 6.5 Hz), 3.73 (s,
3H, OCH3), 4.05 (m, NH), 6.76-7.64 (m, 4H); 13C NMR
(CDCl3) δ = 13.5, 21.8, 32.4, 33.9, 43.7, 55.6, 112.5, 114.9,
134.5, 152.4, 222.5 (C=S) ppm; MS (EI): m/z = 270; Analysis:
C12H18N2OS2, calcd.: C, 53.30; H, 6.71; N, 10.36; S, 23.72%;
found: C, 53.24; H, 6.65; N, 10.33; S, 23.58%.
Typical Experimental Procedure for the Synthesis of
Carbazates
Substituted hydrazine (7.56 mmol) was taken in dry DMSO
(25 ml) and purified gaseous CO2 was bubbled in it for 30 min
at room temperature. To this, a mixture of triphenylphosphine
(7.56 mmol) and diethyl azodicarboxylate (7.56 mmol) was
added slowly in 2-3 small portions. Next, corresponding
alcohol (7.56 mmol) was added in it with constant stirring at
room temperature. The reaction was continued until
completion (cf Table 1) as confirmed by TLC. The reaction
mixture was then poured into distilled water (50 ml) and
extracted with ethyl acetate thrice. The organic layer was
separated and dried over anhydrous sodium sulphate and then
concentrated to afford the desired carbazate compound.
N’-(4-Methoxyphenyl) hydrazinecarboxylic acid n-
butyl ester (Table 1, entry 1, C12H18N2O3). Yield: 94%;
m.p.: yellow oil; IR (neat) ϋ = 1690 cm-1; 1H NMR (300 MHz,
CDCl3) δ = 0.96 (t, 3H, CH3), 1.35 (m, 2H, CH2CH3), 1.60 (m,
2H, CH2), 3.73 (s, 3H, OCH3), 4.12 (t, 2H, J = 6.5 Hz, OCH2),
5.20 (br, s, NH), 6.75-7.66 (m, 4H, Ar-H), 8.05(s, NH); 13C
NMR (100 MHz, CDCl3) δ = 14.8, 21.8, 32.4, 33.9, 55.6,
112.5, 114.9, 134.5, 153.4, 160.5 (C=O) ppm; MS (EI): m/z =
238; Analysis: C12H18N2O3, calcd.: C, 60.49; H, 7.61; N,
11.76%; found: C, 60.67; H, 7.44; N, 11.56%.
RESULTS AND DISCUSSION
Synthesis of a carbazate compound was achieved through
the reaction of the corresponding alcohol with a suitable
substituted hydrazine using Mitsunobu’s reagent/CO2 system
at room temperature. The product was observed and confirmed
by the various spectroscopic and analytical techniques. Thus, a
variety of primary, secondary and tertiary alcohols underwent
through the Mitsunobu coupling reaction with a variety of
substituted aliphatic/aromatic hydrazines using gaseous carbon
dioxide to afford the corresponding carbazates in high yields
(80-98%) as mentioned in Table 1. To the best of our
knowledge this is the first report for the direct synthesis of
carbazates from the corresponding alcohols using Mitsunobu’s
reagent/CO2 system at room temperature. The reaction-
conditions have been depicted in Scheme 1.
The synthesis of dithiocarbazate compound was achieved
through the direct reaction of an alcohol with a substitiuted
hydrazine using Mitsunobu’s reagent/CS2 system at room
temperature. The structure was further confimed through
various spectroscopic and analytical techniques. It was further
reallized that the reaction of dithiocarbazate formation is faster
as compared to carbazate, perhaps may be due to the greater
Typical Experimental Procedure for the Synthesis of
Dithiocarbazates
Substituted hydrazine (7.56 mmol) was taken in dry
DMSO (25 ml) and CS2 (11.34 mmol) was added dropwise in
it for 30 min at room temperature. To this, a mixture of
397

An Efficient One-Pot Synthesis of Carbazates and Dithiocarbazates
Table 1. Conversion of Various Alcohols into Carbazates of General Formula Ia of Scheme 1
Entry
R1
R2
R3
R
Time (h)
Isolated yield
(%)
94
90
86
92
87
83
82
80
83
88
82
90
92
98
86
85
1
2
3
4
5
6
7
8
n-C3H7
PhCH2CH2
PhCH2
Ph
H
H
H
H
Me
H
H
H
H
H
n-C4H9
H
H
H
n-C3H7
CH3
H
H
H
H
H
H
H
H
H
H
n-C4H9
H
H
H
H
H
4-MeOPh
Ph
Ph
n-C4H9
n-C4H9
3-NO2Ph
4-NO2Ph
2,4-NO2Ph
Naphthyl
Ph
Ph
n-C4H9
Ph
n-C4H9
Ph
Ph
2.5
2.5
3.0
2.5
2.0
3.5
3.5
4.0
3.5
2.5
4.0
2.5
2.5
2.0
2.5
2.5
C2H5
4-MeOPh
n-C3H7
n-C3H7
n-C3H7
n-C4H9
n-C4H9
n-C5H11
n-C7H15
n-C9H19
n-C3H7
Ph
9
10
11
12
13
14
15
16
aAll the products were characterized by IR, NMR and mass spectral data.
O
R1
R3
R1
R3
R
Dry DMSO, DEAD/Ph3P
CO2, RT, 2-4h
R2
OH
R2
O
H2N NH
R
+
N
H
NH
I
Scheme 1
reactivity of CS2 as compared to CO2. Thus, various kinds of
dithiocarbazates were prepared through the reaction of various
kinds of structurally diverse primary, secondary and tertiary
alcohols with variety of substituted hydrazines using
Mitsunobu’s reagent/CS2 system, to afford the corresponding
dithiocarbazates in high yields (82-98%) as mentioned in
Table 2. To the best of our knowledge this is the first report
for the direct synthesis of dithiocarbazates from the
corresponding alcohols using Mitsunobu’s reagent/CS2
system. The whole reaction conditions are depicted in Scheme
2.
chloroform, DMSO, dimethylformamide, hexamethyl-
phosphoric triamide of which dry DMSO proved to be most
suitable at room temperature for caring out the synthesis of
carbazates and dithiocarbazates.
In conclusion, we have developed a convenient and
efficient protocol for one-pot, three components coupling of
various alcohols with variety of substituted hydrazines via
Mitsunobu’s reagent/CO2 and Mitsunobu’s reagent/CS2
system. This reaction generates the corresponding,
carbazates/dithiocarbazates in excellent yields at room
temperature. Furthermore, this method exhibits substrate
versatility, mild reaction conditions and experimental
convenience. This synthetic protocol is believed to offer a
We tried many solvents like, n-heptane, n-hexane,
acetonitrile, benzene, toluene, methanol, dichloromethane,
398

Chaturvedi et al.
Table 2. Conversion of Various Alcohols to Dithiocarbazates of General Formula IIa of Scheme 2
Entry
R1
R2
R3
R
Time (h)
Isolated yield
(%)
95
91
87
91
88
84
83
82
84
89
83
92
94
98
87
86
1
2
3
4
5
6
7
8
n-C3H7
PhCH2CH2
PhCH2
Ph
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
4-MeOPh
Ph
Ph
n-C4H9
n-C4H9
3-NO2Ph
4-NO2Ph
2,4-NO2Ph
Naphthyl
Ph
Ph
n-C4H9
Ph
n-C4H9
Ph
Ph
1.5
1.5
2.0
1.5
1.0
2.5
2.5
3.0
2.5
1.5
2.0
1.5
1.5
1.0
1.5
1.5
C2H5
4-MeOPh
n-C3H7
n-C3H7
n-C3H7
n-C4H9
n-C4H9
n-C5H11
n-C7H15
n-C9H19
n-C3H7
Ph
9
10
11
12
13
14
15
16
n-C4H9 n-C4H9
H
H
H
n-C3H7
CH3
H
H
H
H
H
aAll the products were characterized by IR, NMR and mass spectral data.
S
R1
R3
R1
R3
R
dry DMSO, DEAD/Ph3P
CS2, RT, 1-3h
R2
OH
R2
S
NH2 NH
R
+
NH NH
II
Scheme 2
more general method for the formation of C-O, C-S and C-N
bonds essential to numerous organic syntheses.
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Fehmida, A. Bhattacharya, S. Bhattacharya, A. Azam,
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