Synthesis of isocyanates from carbamate esters employing boron trichloride

Article abstract of DOI:10.1039/a807287f

The conversion of carbamate esters to isocyanates and diisocyanates of industrial importance is possible using BCl₃ in the presence of Et₃N; the reaction is simple in execution and work-up, occurring under mild conditions and affording isocyanates in excellent yields.

Full text of DOI:10.1039/a807287f

Synthesis of isocyanates from carbamate esters employing boron trichloride
D. C. D. Butler and H. Alper*
Department of Chemistry, University of Ottawa, 10, Marie Curie, Ottawa, Ontario, Canada K1N 6N5
Received (in Corvallis, OR, USA) 17th September 1998, Accepted 21st October 1998
The conversion of carbamate esters to isocyanates and
diisocyanates of industrial importance is possible using BCl3
in the presence of Et3N; the reaction is simple in execution
and work-up, occurring under mild conditions and affording
isocyanates in excellent yields.
Table 1 Conversions of carbamate esters to the corresponding isocyanates
using BCl3
Yield
(%)c
Substratea
Productb
R
Me 87 (72)d
Presently, isocyanates are manufactured on a commercial scale
by reaction of phosgene with amine or amine salt precursors.1
As restrictions upon the use of very toxic materials such as
phosgene and other chlorine-containing compounds within the
chemical industry have become more rigorously enforced, there
has been increasing interest in developing alternative methods
for isocyanate production.2 One such method (Scheme 1)
Et
Pr
93
88
RO2CHN
RO2CHN
NHCO2R OCN
NCO
Me 90 (79)d
Et
Pr
100
100
NHCO2R
OCN
OCN
NCO
NHCO2R
NCO
Me
Me 92 (70)d
Et
Pr
90
94
RO2CHN
Me
H2O
RNH2
+
CO
+
1/2 O2
+
R′OH
NHCO2R
NCO
Me 98
Et
100
RNHCO2R′
NHCO2R
NCO
RNO2
+ 3CO
+
R′OH
Me
Me
Me
Me
2CO2
Me 91
Et
100
Scheme 1
RO2CHN
NHCO2R
OCN
NCO
involves the catalytic production of carbamate esters (by
reductive carbonylation of nitro derived compounds,3 or
oxidative carbonylation of amines4,3b), dealcoholysis of which
gives isocyanates. One of us showed recently that elimination of
alcohol from carbamate esters to yield isocyanates can be
facilitated using chlorocatecholborane in toluene, in the pres-
ence of Et3N (Scheme 2).5 This paper demonstrated that the way
in which the alcohol product is irreversibly removed from the
reaction solution, in the form of an alkyl catecholborate, is
pertinent to the significance of this method compared with those
which employ the thermal decomposition of carbamate esters,
in which recombination of the resulting isocyanate with alcohol
is possible.
Me 93 (57)d
RO2CHN
OCN
Et
94
Cl
Cl
Me 87
Et 97
RO2CHN
Cl
OCN
O
Cl
O
S
Me 92
RO2CHN
Me
OCN
S
Me
Et
100
O
O
NHCO2R
NCO
Et
100
O
O
O
O
+
B
Cl
Scheme 2
B
OR′ + RNCO
RNHCO2R′
Me 71
Et 86
NHCO2R
NCO
NHCO2R
Me
NCO
Having demonstrated the use of chlorocatecholborane in this
type of reaction, we reasoned that simple boron halides, BX3 (X
= Cl, Br), may also be active as cheap alternatives. Addition-
ally, it has previously been shown that BX3 can be generated in
the production of benzyl esters by reaction of trialkyl borates
with benzylic halides and CO in the presence of catalytic
quantities of Pd0 or RhI.6 This offers the rather attractive option
of two concomitant processes achieving commercially valuable
ends together with constant recycling of boron.
Boron trihalides are known for their strong Lewis acid
character, and for their ability to cleave a wide variety of ethers,
acetals and esters under relatively mild conditions.7 In pursuit of
alternative methods of isocyanate production, we now report the
results of our work with BBr3 and BCl3 in facilitating the
conversion of carbamate esters to isocyanates of industrial
importance.
Mee 73
Ete 68
Me
Me
NHCO2R
NCO
Me
Me
Me
NHCO2R
NCO
Mee 68
Ete 79
NHCO2R
NCO
a
1
Purities of the carbamate esters were assessed by H NMR analysis and
melting points. Reaction conditions: isocyanates: BCl3 (0.37 equiv.), NEt3
(1.1 equiv.), refluxing benzene, 0.5 h; diisocyanates: BCl3 (0.74 equiv.),
NEt3 (2.2 equiv.), refluxing benzene, 0.5 h. Product isocyanates were
identified by GC–MS and GC analysis compared with authentic materials.
c Yields by GC analysis with tetradecane as the internal calibrant. d Mixture
of cis and trans isomers. Yields of pure products isolated by vacuum
distillation, characterized by 1H NMR, 13C NMR, IR and MS analysis and
by comparison with authentic materials.
b
e
Treatment of a carbamate ester with 0.37 equiv. of BCl3 and
1.1 equiv. of Et3N, for 30 min in refluxing benzene, afforded the
Chem. Commun., 1998, 2575–2576
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Base
However, we found that PCl3, when used instead of BCl3, is
capable of less than ca. 5% conversion of carbamate esters to
isocyanates. Similar yields were attained with AlCl3, and TiCl4
was found to be totally inactive. It is conceivable that PCl3 can
react as an electrophile at nitrogen in this case, and a possible
reason for its overall inactivity is the inability to promote
cleavage of an alkoxy group from the resulting intermediate.
In conclusion, BCl3 is an excellent, efficient and economical
reagent for the synthesis of mono- and di-isocyantes in high
yield.
H
N
BX2
N
O
O
RNCO
+
BX2(OR′)
R
R′
R
R′
O
O
X2B
X = Cl or OR′
Cl
BaseH+
Scheme 3
We are grateful to the Environmental Science and Technol-
ogy Alliance Canada (ESTAC) for support of this research.
isocyanate in good yield. In most cases, quantitative or near-
quantitative conversion to the product isocyanates was obtained
under these relatively mild reaction conditions for a series of
aryl, alkyl, alicyclic and tosyl carbamate esters. The reactions
were found to be highly selective with only the product
isocyanates, partially cleaved carbamate esters (where dicarba-
mate esters were employed as starting materials), or starting
materials being observed in the final solutions. The product
isocyanates can usually be easily isolated by evaporation of the
solvent and trialkyl borate under reduced pressure followed by
vacuum distillation at elevated temperature. For example,
toluene-2,4-diyl diisocyanate (TDI), para-phenylene diisocya-
nate (PDI) and 4,4A-methylenebis(phenyl isocyanate) (MDI),
which are large-scale raw materials for the manufacture of
polyurethane foams,8 can be isolated as spectroscopically pure
materials from their corresponding methyl carbamate esters in
70–79% yield. Toluene-2,4-diyl diisocyanate can also be
isolated in good yield from its methyl carbamate ester when the
reaction is performed in toluene (65% isolated yield) or hexanes
(41% isolated yield). Chlorinated solvents, however, are not
suitable media for this reaction. As expected, BCl3 is converted
to trialkyl borate (identifiable by GC–MS), observed after the
reaction, consistent with the reaction shown in Scheme 3.
BBr3, a stronger Lewis acid than BCl3, was also effective in
this reaction, with isocyanate yields being similar to those
quoted for BCl3 in Table 1. However, appreciable amounts of
amine were also produced in some cases bringing the selectivity
of this reagent into question.
Notes and references
1 P. Braunstein, Chem. Rev., 1989, 89, 1927; G. Ortel, Polyurethane
Handbook, Hanser, Munich, 1985; H. Twichett, Chem. Rev., 1974, 74,
209.
2 Kirk-Othmer, Encyclopaedia of Chemical Technology, 4th edn., Wiley,
New York, 1995, vol. 14, p. 902.
3 (a) S. J. Skoog and W. L. Gladfelter, J. Am. Chem. Soc., 1997, 119,
11049; (b) A. M. Tafesh and J. Weiguny, Chem. Rev., 1996, 96, 2035; (c)
P. Wehman, P. C. J. Kamer and P. W. N. M. van Leeuwen, Chem.
Commun., 1996, 217; (d) I. Pri-Bar and J. Schwartz, J. Org. Chem., 1995,
60, 8124; (e) V. L. K. Valli and H. Alper, J. Am. Chem. Soc., 1993, 115,
3778 and references cited therein.
4 V. L. K. Valli and H. Alper, Organometallics, 1995, 14. 80; T. W. Leung
and B. D. Dombek, J. Chem. Soc., Chem. Commun., 1992, 205; S. Cenini,
M. Pizzotti and C. Crotti, in Aspects of Homogeneous Catalysis, ed. R.
Ugo, Reidel, Dordrecht, The Netherlands, 1988, vol. 6, p. 97 and
references cited therein.
5 V. L. K. Valli and H. Alper,. J. Org. Chem., 1995, 60, 257.
6 H. Alper, H. Hamel, D. J. H. Smith and J. B. Woell, Tetrahedron Lett.,
1985, 26, 2273; K. E. Hashem, J. B. Woell and H. Alper, Tetrahedron
Lett., 1984, 25, 4879; J. B. Woell and H. Alper, Tetrahedron Lett., 1984,
25, 3791.
7 L. A. Paquette, Encyclopaedia of Reactants for Organic Synthesis,
Wiley, Chichester, 1995, p 645.
8 Kirk-Othmer, Encyclopaedia of Chemical Technology, 4th edn., Wiley,
New York, 1997, vol. 24, p. 695.
9 D. Riley, W. D. McGhee and T. Waldman, ACS Symp. Ser., 1994, 577,
122.
It has previously been shown that PCl3, and other Lewis
acids, can effect the removal of OH from carbamate anions to
yield isocyanates by electrophilic, oxophilic dehydration.9
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Chem. Commun., 1998, 2575–2576