Synthesis and characterization of asymmetric substituted dicarbamates

Article abstract of DOI:10.1016/j.cclet.2011.05.009

Several new asymmetric substituted dicarbamates were synthesized with a convenient route. Firstly, tolylene-2, 4-diisocyanate dimmer was obtained from monomer with tributylphosphine as catalyst. Then, the dimmer reacted with alcohol (R¹OH) to p

Full text of DOI:10.1016/j.cclet.2011.05.009

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 1167–1170
www.elsevier.com/locate/cclet
Synthesis and characterization of asymmetric substituted
dicarbamates
*
Chao Zhao, Peng Fei Yang , Shun Ping Wang, Jun Ying Li, Tian Duo Li
*
Shandong Provincial Key Laboratory of Fine Chemicals, Shandong Polytechnic University, Jinan 250353, China
Received 21 January 2011
Available online 20 July 2011
Abstract
Several new asymmetric substituted dicarbamates were synthesized with a convenient route. Firstly, tolylene-2, 4-diisocyanate
dimmer was obtained from monomer with tributylphosphine as catalyst. Then, the dimmer reacted with alcohol (R1OH) to prepare
carbamate substituted uretidione. Finally, uretidione ring was opened and the released isocyanate reacted with another alcohol
(R2OH, R1 ¼ R2).
# 2011 Tian Duo Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Asymmetric substituted dicarbamates; Tolylene-2, 4-diisocyanate; Uretidione
Carbamates are a kind of significant compounds which have been used in many areas, such as intermediates of
organic synthesis, pesticides and weedicides [1,2]. As a kind of special carbamate, asymmetric substituted
dicarbamate has been continuously investigated [3–5]. There are two traditional routes to synthesize asymmetric
substituted dicarbamate (Scheme 1). In the early days, they were prepared from 2, 4-dinitrotolylene and carbon
monoxide. Lick [6] used 2, 4-dinitrotolylene and carbon monoxide to react with ethanol (125 8C, 3000 psi) and
methanol (175 8C, 4775 psi) in the presence of amorphous rhodium sesquioxide, respectively. The mixture of 4a and
4b was acquired with that method. However, it was very difficult to separate those two compounds and the reaction
condition was very harsh. Afterwards, Schulze [7,8] prepared asymmetric substituted dicarbamates with 2-nitro-4-
aminotolylene. Firstly, amido was transformed into isocyanate and reacted with R1OH, or amido reacted with
R1OCOCl directly, through which the first carbamate group was introduced; secondly, nitryl was reduced to amido,
transformed into isocyanate and reacted with R2OH, or the amino reacted with R2OCOCl directly, through which the
second carbamate group was introduced. Pure compounds could be obtained, but it was very inconvenient in procedure
and harsh in reaction conditions.
In this paper, we synthesized several asymmetric substituted dicarbamates with a convenient route (Scheme 2). It
was divided into three steps. Firstly, tolylene-2, 4-diisocyanate was dimerized with tributylphosphine as catalyst.
Then, tolylene-2, 4-diisocyanate dimmer reacted with alcohol (R1OH) to prepare carbamate substituted uretidione.
Finally, uretidione ring was opened with tributylphosphine as catalyst, in order that the released isocyanate reacted
* Corresponding authors.
E-mail addresses: ypfyyh@gmail.com (P.F. Yang), litianduo@163.com (T.D. Li).
1001-8417/$ – see front matter # 2011 Tian Duo Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.05.009

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C. Zhao et al. / Chinese Chemical Letters 22 (2011) 1167–1170
CH3
NO2
CH3
NO2
NH2
COCl2
CO, R1OH
Red.
NHCOOR1
CH3
CH3
CH3
NH2
NCO
NO2
R1OCOCl
NO2
R2OCOCl
NHCOOR1
NHCOOR1
CH3
CH3
R2OH
R1OH
CO, R2OH
NHCOOR2
NO2
COCl2
NHCOOR1
NCO
Scheme 1. Traditional synthetic routes of asymmetric substituted dicarbamate.
CH3
CH3
NCO
O
NHCOOR1
CH3
CH3
NHCOOR1
NCO
R2OH
P(Bu)3
R1OH
P(Bu)3
N
N
O
C
C
O
C
C O
N
N
NHCOOR2
NCO
2
1
4
3
NCO
NHCOOR1
CH3
CH3
Scheme 2. New synthetic route of asymmetric substituted dicarbamate.
with another alcohol (R2OH, R1 ¼ R2). A series of asymmetric substituted dicarbamates was prepared, four of which
was not reported before.
Tolylene-2, 4-diisocyanate dimmer 2 was obtained from monomers 1. Dimerization of isocyanate was a reversible
reaction in the presence of catalysts or elevated temperature [9]. In order to get a better yield, tributylphosphine was
used as catalyst and the reaction was carried on at relatively low temperature. The dimerization reaction was used to
protect one active isocyanate group, and make the other isocyanate reacted with R1OH. IR, NMR and elemental
analysis showed that the protected isocyanate could not react with R1OH [10].
After dimmerization and carbamation with R1OH, uretidione ring must be opened to generate asymmetric
substituted dicarbamate. It was reported that [11] uretidione ring could broken at above 150 8C. In the presence of
catalyst, such as trialkylphosphines, the dissociation temperature maybe decreased. For example, uretidione
dissociated slightly at 25 8C and completely dissociated at 80 8C in the presence of trialkylphosphines [12]. Thus,
tributylphosphine was used once again, yet the purpose was to open uretidione ring at elevated temperature after 3a–3c
were synthesized. The blocked isocyanate could be set free and react with R2OH to synthesize 4a–4i (Table 1). 4f, 4g,
4h, 4i were not reported before.
Tolylene-di-(2-isopropyl-4-ethyl)-carbamate (4f): colorless crystal, yield 89%, mp 142–143 8C. Calcd. C, 59.96;
H, 7.18; N, 9.99. Found: C, 59.86; H, 7.07; N, 10.04. H NMR (400 MHz, DMSO-d6): d 1.22 (d, 6H, J = 6.5 Hz),
1

C. Zhao et al. / Chinese Chemical Letters 22 (2011) 1167–1170
1169
Table 1
Asymmetric substituted dicarbamates (4f, 4g, 4h, 4i were not reported before).
Compound Structure
Compound Structure
Compound Structure
NHCOOCH2CH3
NHCOOCH3
CH3
CH3
4a
4d
4g
NHCOOCH2
CH3
CH3OCOHN
(CH3)2CHOCOHN
CH3OCOHN
NHCOOCH(CH3)2
NHCOOCH3
CH3
CH3
4b
4e
4f
4h
CH3CH2OCOHN
CH3CH2OCOHN
NHCOOCH2
CH3
CH3CH2OCOHN
NHCOOCH(CH3)2
NHCOOCH2CH3
CH3
CH3
4c
4i
(CH3)2CHOCOHN
CH3OCOHN
NHCOOCH2
CH3
(CH3)2CHOCOHN
2.09(s, 3H), 4.06(q, 2H, J = 7.1 Hz), 4.83(m, 1H, J = 6.2 Hz), 7.02–7.48(m, 3H), 8.66(s, 1H), 9.47(s, 1H). 13C NMR
(100 MHz, DMSO-d6): d 13.99, 16.57, 21.45, 59.44, 66.79, 114.43, 114.47, 125.06, 129.57, 136.02, 136.66, 152.98,
153.36. IR (KBr, cmꢀ1): 3331.07, 3302.13, 1695.43.
Tolylene-di-(2-methyl-4-benzyl)-carbamate (4g): colorless crystal, yield 72%, mp 129–130 8C. Calcd. C, 64.96; H,
5.77; N, 8.91. Found: C, 64.88; H, 5.72; N, 9.03. 1H NMR (400 MHz, DMSO-d6): d 2.03(s, 3H), 3.56(s, 3H), 5.05(s,
2H), 6.97–7.44 (m, 8H), 8.74(s, 1H), 9.60(s, 1H). 13C NMR (100 MHz, DMSO-d6): d 16.53, 51.05, 65.07, 114.37,
114.53, 125.16, 127.43, 127.45, 127.88, 129.69, 135.94, 136.20, 136.56, 152.80, 154.18. IR (KBr, cmꢀ1): 3259.70,
1712.79, 1693.50.
Tolylene-di-(2-ethyl-4-benzyl)-carbamate (4h): colorless crystal, yield 68%, mp 119–120 8C. Calcd. C, 65.84; H,
6.14; N, 8.53. Found: C, 65.62; H, 6.14; N, 8.55. 1H NMR (400 MHz, DMSO-d6): d 1.15 (t, 3H, J = 6.9 Hz), 2.04 (s,
3H), 4.02 (q, 2H, J = 6.9 Hz,), 5.05 (s, 2H), 6.97–7.44 (m, 8H), 8.68 (s, 1H), 9.59 (s, 1H). 13C NMR (100 MHz,
DMSO-d6): d 14.06, 16.56, 59.55, 65.06, 114.40, 114.46, 125.16, 127.42, 127.44, 127.87, 129.66, 136.01, 136.20,
136.53, 152.80, 153.73. IR (KBr, cmꢀ1): 3271.27, 1710.86, 1693.50.
Tolylene-di-(2-isopropyl-4-benzyl)-carbamate (4i): colorless crystal, yield 78%, mp 130–131 8C. Calcd. C, 66.65;
H, 6.48; N, 8.18. Found: C, 66.62; H, 6.44; N, 8.17. 1H NMR (400 MHz, DMSO-d6): d 1.15 (d, 6H, J = 6.2 Hz), 2.04 (s,
3H), 4.78 (m, 1H, J = 6.2 Hz, 12.5 Hz), 5.06 (s, 2H), 6.97–7.45 (m, 3H), 8.62 (s, 1H), 9.60 (s, 1H). 13C NMR
(100 MHz, DMSO-d6): d 16.59, 21.45, 65.06, 66.81, 114.41, 125.16, 126.02, 127.42, 127.44, 127.87, 129.64, 136.09,
136.21, 136.51, 152.81, 153.36. IR (KBr, cmꢀ1): 3331.07, 3302.13, 1695.43.
1. Experimental
IR: Bruker TENSOR27. NMR: Bruker AVANCE II 400. Elemental analysis: Elementar VARIOE III.
Tolylene-2, 4-diisocyanate was purchased from Sigma–Aldrich Co., Ltd. and used after vacuum distillation.
Tributylphosphine was purchased from TCI (Shanghai) Development Co., Ltd. and used received. Other organic
solvents were purchased from Sinopharm Chemical Reagent Co. Ltd. and used after distillation or vacuum distillation.
Synthesis of tolylene-2, 4-diisocyanate dimmer (2): Tolylene-2, 4-diisocyanate 1 (8.708 g, 50 mmol) was fully
dissolved in toluene (50 mL), to this was added tributylphosphine (3% m/m). The reaction was carried on with
magnetic stirrer at 0 8C for 3 h. After that, the mixture was filtered, washed for three times and dried. The product 2
was recrystallized from petroleum ether and dried in vacuum for 24 h.
Synthesis of 1, 3-Diazetidine-2, 4-dione, 1, 3-bis(3-lcarbamato-4-methylphenyl) (3): Tolylene-2, 4-diisocyanate
dimer 2 (0.696 g, 2.0 mmol) was fully dissolved in chlorobenzene (50 mL), to this was added R1OH (10 mmol). The

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C. Zhao et al. / Chinese Chemical Letters 22 (2011) 1167–1170
reaction was carried on with magnetic stirrer at 60 8C for 3 h. The mixture was filtered and the residue 3 was washed
with chlorobenzene, dried under vacuum at 60 8C for 24 h.
Synthesis of asymmetric substituted dicarbamates (4): 3 (1.0 mmol) was fully dissolved in DMF (15 mL). R2OH
(R1 ¼ R2) (10 mmol) and tributylphosphine (3% m/m) was added. The reaction was carried on with magnetic stirrer at
60 8C for 3 h. The mixture was filtered and the filtrate 4 was dried under vacuum at 90 8C for 48 h to remove the
solvent. The remaining solid was recrystallized in DMF/H2O (3:7).
Acknowledgment
The authors are grateful for the financial support from the National Natural Science Foundation of China (No.
20676074).
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(400 MHz, DMSO-d6): d 2.18 (s, 3H), 3.67 (s, 3H), 7.11–7.57 (m, 3H), 8.94 (s, 1H). IR (KBr, cmꢀ1): 3295.96, 1779.55, 1703.32. 3b: white
powder, yield 94%. Calcd. C, 59.97; H, 5.50; N, 12.73. Found: C, 59.71; H, 5.37; N, 12.57. 1H NMR (400 MHz, DMSO-d6): d 1.24 (t, 3H,
J = 7.0 Hz), 2.17 (s, 3H), 4.09 (q, 2H, J = 6.9 Hz), 7.10–7.57 (m, 3H), 8.92 (s, 1H). IR (KBr, cmꢀ1): 3296.51, 1780.50, 1699.14. 3c: white
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J = 6.2 Hz), 2.17 (s, 3H), 4.85 (m, 1H, J = 12.4), 7.07–7.57 (m, 3H), 8.83 (s, 1H). IR (KBr, cmꢀ1): 3288.72, 1785.85, 1695.95.
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