Comparison of base-promoted and self-catalyzed conditions in the synthesis of isocyanates from amines using triphosgene

Article abstract of DOI:10.1080/00397910601055156

Comparison of base-promoted and self-catalyzed conditions for the synthesis of isocyanates from amines and triphosgene shows no advantage in using an amine base in the majority of cases. The workup and isolation of the product is simplified under base-free conditions. Yields of between 50 and 90% after distillation were common. Only acid-sensitive substrates need a base catalyst. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910601055156

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Comparison of Base‐Promoted and Self‐Catalyzed
Conditions in the Synthesis of Isocyanates from Amines
Using Triphosgene
Yiannis C. Charalambides a & Stephen C. Moratti a
a Melville Laboratory for Polymer Synthesis, Department of Chemistry, University of
Cambridge, United Kingdom
Version of record first published: 24 Feb 2007.
To cite this article: Yiannis C. Charalambides & Stephen C. Moratti (2007): Comparison of Base‐Promoted and Self‐Catalyzed
Conditions in the Synthesis of Isocyanates from Amines Using Triphosgene, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 37:6, 1037-1044
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Synthetic Communicationsw, 37: 1037–1044, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910601055156
Comparison of Base-Promoted and Self-
Catalyzed Conditions in the Synthesis of
Isocyanates from Amines Using Triphosgene
Yiannis C. Charalambides and Stephen C. Moratti
Melville Laboratory for Polymer Synthesis, Department of Chemistry,
University of Cambridge, United Kingdom
Abstract: Comparison of base-promoted and self-catalyzed conditions for the
synthesis of isocyanates from amines and triphosgene shows no advantage in using
an amine base in the majority of cases. The workup and isolation of the product is sim-
plified under base-free conditions. Yields of between 50 and 90% after distillation were
common. Only acid-sensitive substrates need a base catalyst.
Keywords: amines, isocyanates, triphosgene
Isocyanates constitute the most important commercial precursors in the
synthesis of polyurethanes and are manufactured on a very large scale for a
broad range of applications.[1,2] Presently, all current commercial processes
dealing with the synthesis of isocyanates that are practiced on a significant
industrial scale make use of the phosgenation of both aliphatic and aromatic
amines.[3–8] This process attracts much attention owing to the more rigorously
enforced restrictions placed by the chemical industry upon the use of toxic
materials such as phosgene and other chlorine-containing compounds. In
light of this, there has been a growing interest in the past decade for the devel-
opment of alternative methods and reagents for the production of isocyanates,
especially on a laboratory scale.[9–17] One such reagent is triphosgene
[bis(trichloromethyl)carbonate, or BTC], which can be used as an alternative
Received in the U.K. November 1, 2004
Address correspondence to Stephen C. Moratti, Melville Laboratory for Polymer
Synthesis, Department of Chemistry, University of Cambridge, Lensfield Road, CB2
1EW, United Kingdom. E-mail: scm1001@cam.ac.uk
1037

1038
Y. C. Charalambides and S. C. Moratti
synthetic auxiliary in the preparation of isocyanates.[18–23] Despite the
preparation of triphosgene being dated back to 1800 by Councler,[24] only
comparatively recently has its use in the preparation of isocyanates been
widely utilized. The advantages of triphosgene can be attributed to the fact
it is a crystalline solid (mp 808C, bp 2068C).[19] This makes it easier to use,
handle, and transport owing to its lower vapor pressure and higher stability
in comparison to the gaseous equivalent phosgene and the liquid equivalent
diphosgene.[20]
The synthesis of isocyanates using triphosgene has been carried out both
in the presence[19–23] and much less commonly in the absence[23] of an amine
base. However, it is not clear from the literature why the conditions chosen in
each case were used or whether they were optimized. In general, the presence
of an amine complicates workup and is obviously less atom efficient. The self-
catalyzed route becomes quite acidic because HCl is released by the reaction,
and it is not suited for acid-sensitive materials. However, for the majority of
substrate, HCl is not an obvious problem, and so we decided to test a range
of substrates.
A series of aliphatic and aromatic mines were either bought or syn-
thesized. These were then subjected to standard conditions as described in
the experimental section. We found that ethyl acetate proved to be a good
solvent for the self-catalyzed conditions. However, other solvents such as
p-dioxane are equally effective.
The results can be seen in Table 1. Reaction times of 4 h proved to be
enough in all cases. The crude yields in the self-catalyzed examples looked
to be well in excess of 90%, and the resulting crude materials were usually
Table 1. Yields of isocyanates using base or self-catalyzed methods
Yield (%)
Entry
Bp (mm Hg, 8C)
Base prompted
Self-catalyzed
1
2
0.3, 230
1, 150
1, 160
20, 125
26, 170
6, 150
5, 235
5, 250
7, 150
50, 100
6, 130
1, 140
1, 170
1, 210
82
62
65
59
80
76
74
67
68
46
54
61
71
59
87
60
67
66
70
80
66
62
74
56
94
90
77
63
3
4
5
6
7
8
9
10
11
12
13
14

Isocyanates from Amines
1039
good enough to be used without distillation. In almost all cases, the self-
catalyzed route is an efficient or more efficient than the use of triethylamine
as an HCl scavenger/catalyst. It should be noted that these reactions looked
quite clean and that the cited yields were all after distillation. On the other
hand, triethylamine hydrochloride often proved hard to get rid off in the
base-promoted route, and traces could sometimes be found in the product
even after distillation (Scheme 1 and Figure 1).
Thus, the absence of the base makes workup a lot less time consuming
and tedious, with yields of the desired product comparable to those obtained
under the base-promoted conditions and in some cases higher. We have
therefore come to the conclusion that the use of the amine base is not
required in the majority of cases for the synthesis of both aliphatic and
aromatic isocyanates from their respective amines.
EXPERIMENTAL
Typical Procedures
Both procedures involve the potential release of gaseous phosgene and
hydrogen chloride, and good containment procedures should be adopted.
4-Isocyanato-3-methyl-1-octyloxybenzene 1
Base Promoted
To a stirring solution of triphosgene (1.26 g, 4.24 mmol, 0.5 equiv) in dry
benzene (15 mL), Et3N (1.18 mL, 8.50 mmol, 1 equiv) was added. While the
reaction was slowly brought to reflux, 2-methyl-4-octyloxyphenylamine
(2.0 g, 8.50 mmol) in dry benzene (10 mL) was added slowly. The reaction
mixture was then refluxed and stirred under nitrogen for 4 h. After allowing
the reaction mixture to cool to rt, the precipitated white solid was filtered
and the filtrate evaporated under reduced pressure. The residue obtained
was diluted with DCM (40 mL) and washed with 10% 10 M HCI
(2 ꢀ 30 mL). The organic layer was then wased with water (2 ꢀ 40 mL),
Scheme 1. Conditions employed for isocyanate synthesis.

1040
Y. C. Charalambides and S. C. Moratti
Figure 1. Structures of isocyanates prepared.
and dried over anhydrous MgSO4, the solvent was evaporated under reduced
pressure, and the residue obtained was subjected to distillation in a Kugelrohr
apparatus, affording 1 (1.78 g, 82%) as a yellow liquid: bp (0.3 mm Hg,
2308C); nmax(CDCl3)/cm21 2269 (NCO); dH (400 MHz, CDCl3) 6.94(1H,
d, J 8.8, Ar H), 6.74 (1H, d, J 2.7, Ar H), 6.63 (1H, dd, J 2.7, 8.7, Ar H),
3.91 (2H, t, J 6.6, O-CH2), 2.28 (3H, s, Ar-CH3), 1.72 (2H, tt, J 6.7, 6.7,
O-CH2CH2), 1.50–1.20 [10H, br m, (CH2)5], 0.91 (3H, t, J 7.1, CH3). dC
(125 MHz, CDC13) 156.6, 133.7, 125.4, 124.4, 123.7, 116.3, 112.6, 68.2,
31.5, 29.1, 29.0, 28.9, 25.7, 22.4, 18.3, 13.8.
Self-Catalyzed
To a solution of triphosgene (2.52 g, 8.50 mmol, 0.5 equiv) in EtOAc
(100 mL), 2-methyl-4-octyloxyphenylamine (4.00 g, 17.00 mmol) in EtOAc
(40 mL), was added in small portions. The mixture was then refluxed under

Isocyanates from Amines
1041
nitrogen for 4 h. After allowing the reaction to cool to rt, the solvent was evap-
orated under reduced pressure and the residue obtained was subjected to dis-
tillation in a Kugelrohr apparatus, affording 1 (3.86 g, 87%) as a light yellow
liquid: (0.3 mm Hg, 2308C).
Data
4-Propoxybenzyl Isocyanate 2
Colorless liquid: bp (1 mm Hg, 1508C); nmax(EtOAc)/cm21 2278 (NCO); dH
(400 MHz, CDCl3) 7.22 (2H, d, J 8.7, ArH), 6.86 (2H, d, J 8.7, ArH), 4.39
(2H, s, Ar-CH2), 3.94 (2H, t, J 6.7, O-CH2), 1.78 (2H, sext, J 6.7,
O-CH2CH2), 1.00 (3H, t, J 7.4, CH3); dC (125 MHz, CDCl3) 158.9, 128.9,
128.1, 114.7, 69.6, 46.1, 22.5, 10.5.
3-Propoxybenzyl Isocyanate 3
Colorless liquid: bp (1 mm Hg, 1608C); nmax(EtOAc)/cm21 2282 (NCO); dH
(400 MHz, CDCl3) 7.24 (lH, m, ArH), 6.85 (3H, m, ArH), 4.44 (2H, s,
Ar-CH2), 3.92 (2H, t, J 6.6, O-CH2), 1.81 (2H, sext, J 6.7, O-CH2CH2),
1.03 (3H, t, J 7.4, CH3); dC (125 MHz, CDCl3) 159.5, 138.3, 129.8, 118.7,
113.9, 112.9, 69.5, 46.4, 22.5, 10.5.
1-Octyl Isocyanate 4
Light yellow liquid: bp (20 mm Hg, 1258C) (lit.[17] 15 mm Hg, 858C);
n
max(EtOAc)/cm21 2291 (NCO); dH (400 MHz, CDCl3) 3.27 (2H, t, J 6.7,
CH2-NCO), 160 (2H, tt, J 6.8, 6.8, CH2), 1.42–1.15 [12H, br m, (CH2)6],
0.88 (3H, t, J 6.8, CH3).
4-Butylphenyl Isocyanate 5
Colorless liquid: bp (26 mm Hg, 1708C) (lit.[25] 17 mm Hg, 1218C);
n
max(EtOAc)/cm21 2261 (NCO); dH (400 MHz, CDCl3) 7.10 (2H, t, J 8.4,
ArH), 6.99 (2H, d, J 8.4, ArH), 2.57 (2H, t, J 7.6, Ar-CH2), 1.55 (2H, tt, J
7.7, 7.7, CH2), 1.35 (2H, m, CH2), 0.93 (3H, t, J 7.3, CH3); dC (101 MHz,
CDCl3) 140.3, 130.5, 129.2, 124.2, 34.8, 33.3, 22.0, 13.6.
4-Pentyloxyphenyl Isocyanate 6
Yellow liquid: bp (6 mm Hg, 1508C) (lit.[26] 1.6 mm Hg, 1278C); nmax(CDCl3)/
cm21 2276 (NCO); dH (400 MHz, CDCl3) 6.99 (2H, d, J 9.0, ArH), 6.82 (2H,
d, J 9.0, ArH), 3.91 (2H, t, J 6.6, O-CH2), 1.77 (2H, tt, J 6.8, 6.8, CH2), 1.40
[2H, m, (CH2)2], 0.92 (3H, t, J 7.1, CH3).

1042
Y. C. Charalambides and S. C. Moratti
4-Octyloxyphenyl Isocyanate 7
Yellow liquid: bp (5 mm Hg, 2358C) (lit.[27] 2 mm Hg, 152–1548C);
max(CDCl3)/cm21 2276 (NCO); dH (400 MHz, CDCl3) 6.99 (2H, t, J 9.0,
n
ArH), 6.81 (2H, d, J 9.0, ArH), 3.90 (2H, t, J 6.6, O-CH2), 1.75 (2H, tt,
J 6.9, 6.9, O-CH2CH2), 1.55–1.15 [10H, m, (CH2)5], 0.96 (3H, t, J 6.8,
CH3); dC (101 MHz, CDCl3) 156.7, 125.4, 125.3, 123.9, 115.1, 68.1, 31.5,
29.1, 28.9, 28.8, 25.7, 22.4, 13.8.
4-Decyloxyphenyl Isocyanate 8
Light yellow liquid: bp (5 mm Hg, 2508C); nmax(EtOAc)/cm21 2278 (NCO);
dH (400 MHz, CDCl3) 6.99 (2H, d, J 8.8, ArH), 6.82 (2H, d, J 8.8, ArH), 3.90
(2H, t, J 6.6, O-CH2), 1.75 (2H, tt, J 6.9, 6.9, O-CH2CH2), 1.50–1.20 [14H,
br m, (CH2)7], 0.89 (3H, t, J 6.6, CH3); dC (101 MHz, CDCl3) 156.9, 125.4,
125.3, 123.8, 115.6, 68.1, 31.6, 29.3, 29.1, 29.1, 29.0, 28.9, 25.7, 22.4, 13.8.
4-Iodophenyl Isocyanate 9
White crystals: bp (7 mm Hg, 1508C) (lit.[22] 5 mm Hg, 848C); mp
n
max(CDCl3)/cm21 2287 (NCO); dH (400 MHz, CDCl3) 7.61 (2H, d, J 8.7,
ArH), 6.82 (2H, d, J 8.7, ArH).
Benzyl Isocyanate 10
Colorless liquid: bp (50 mm Hg, 1008C) (lit.[28] 40 mm Hg, 110);
n
max(EtOAc)/cm21 2282 (NCO); dH (400 MHz, CDCl3) 7.42–7.27 (5H,
br m, ArH), 4.49 (2H, s, Ar-CH2).
1-Naphthyl Isocyanate 11
Yellow liquid: bp (6 mm Hg, 1308C) (lit.[29] 20 mm Hg 153–153.58C);
n
max(EtOAc)/cm21 2291 (NCO); dH (400 MHz, CDCl3) 8.08 (1H, dd.
J 1.9, 8.1, ArH), 7.87 (1H, dd, J 1.9, 7.8, ArH), 7.72 (1H, d, J 8.3, ArH),
7.55 (2H, m, ArH), 7.40 (1H, d, J 8.2, ArH), 7.28 (1H, dd, J 1.1, 7.4, ArH).
4,40-Methylendiisocyanate 12
Light yellow solid: bp (1 mm Hg, 1408C) (lit.[30] 5.5 mm Hg 1908C);
n
max(EtOAc)/cm21 2285 (NCO); dH (400 MHz, CDCl3) 7.09 (4H, d, J 8.5,
ArH), 7.00 (4H, d, J 8.5, ArH), 3.91 (2H, s, CH2).

Isocyanates from Amines
1043
4-Iodobenzyl Isocyanate 13
Colorless solid: bp (1 mm Hg, 1708C) nmax(EtOAc)/cm21 2285 (NCO); dH
(400 MHz, CDCl3) 7.66 (4H, d, J 8.3, ArH), 7.08 (2H, d, J 8.3, ArH), 4.46
(2H, s, Ar-CH2); dC (125 MHz, CDCl3) 137.9, 136.5, 128.6, 93.3, 46.0.
bis(2-Isocyanatophenyl)ether 14
Light yellow solid: bp (1 mm Hg, 2108C) nmax(EtOAc)/cm21 2278 (NCO);
dH (400 MHz, CDCl3) 7.20–7.07 (6H, m, ArH), 6.87 (2H, m, ArH); dC
(125 MHz, CDCl3) 150.2, 129.1, 126.5, 125.9, 124.8, 117.9.
ACKNOWLEDGMENTS
The financial support of AWE and discussions with Norman Godfrey (AWE)
are gratefully acknowledged.
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