3940
J. Org. Chem. 1999, 64, 3940-3946
Preparation of Isocyanates from Primary Amines and Carbon Dioxide Using Mitsunobu Chemistry1 Dilek Saylik, Michael J. Horvath, Patricia S. Elmes, and W. Roy Jackson* Department of Chemistry, Monash University, Clayton, Victoria, Australia 3168
Craig G. Lovel and Keith Moody Orica Pty Ltd., Newsom Street, Ascot Vale, Victoria, Australia 3032 Received December 1, 1998
Primary alkylamines 1 and hindered arylamines 1 give high yields of isocyanates 5 when reacted with carbon dioxide and the Mitsunobu zwitterions 4 generated from dialkyl azodicarboxylates and Bu3P in dichloromethane at -78 °C. Use of Ph3P still gave high yields of isocyanates from reactions of primary alkylamines, but only low yields were obtained from reactions of aromatic amines. Reactions which failed to give high yields of isocyanates gave either carbamoylhydrazines 6 and/or dicarbamoylhydrazines 10 and/or triazolinones 7. The triazolinones were shown to arise from reactions of reactive aryl isocyanates with the Mitsunobu zwitterion. The carbamoylhydrazines were shown not to arise from reaction of isocyanate with reduced dialkyl azodicarboxylates, and a mechanism for their formation is proposed. Single-crystal X-ray analyses confirmed the structures of 6, 7, and 10. Introduction 2
The use of polyurethanes continues to grow. All current commercial processes involve the use of isocyanates which have been obtained by reactions of primary amines with phosgene. During the past 20 years a considerable amount of academic- and industrial-based research has been carried out with the aim of developing new commercial routes to isocyanates which do not involve the use of the environmentally unacceptable phosgene. Two main strategies have been pursued. One involves carbonylation of nitroarenes in the presence of an alcohol3 or carbonylation of amines in the presence of an alcohol and an oxidizing agent.4 In each case carbamate esters are formed. Once formed, carbamate esters can, in principle, be thermolyzed to give the corresponding isocyanates. Several patents describe pyrolyses at temperatures greater than 300 °C in the presence of additives, e.g. excess boron,5a bismuth,5a or germanium oxides.5b In general, high yields of isocyanates are not obtained, but recently it has been shown that elimination of methanol from carbamate methyl esters can be achieved using a mixture of chlorocatecholborane and triethylamine to give isocyanates in good yields.6 A second approach involves the * Corresponding author. E-mail:
[email protected], fax: 61 3 9905 4597. (1) Horvath, M. J.; Saylik, D.; Elmes, P. S.; Jackson, W. R.; Lovel, C. G.; Moody, K. Tetrahedron Lett. 1999, 40, 363. (2) Polyurethanes had a global demand of 5.1 × 106 tons per annum in 1990 with an estimated demand of 8.5 × 106 tons per annum in the year 2000. See: Synthetic Polymers, Technology, Properties, Applications; Feldman, D., Barbalata, A., Eds.; Chapman and Hall: London, 1996; p 273. (3) Skoog, S. J.; Gladfelter, W. L. J. Am. Chem. Soc. 1997, 119, 11049. (4) Colquhoun, H. M.; Thompson, D. J.; Twigg, M. V. Carbonylation. Direct Synthesis of Carbonyl Compounds; Plenum Press: New York, 1991; pp 164-171. Fukuoka, S.; Chono, M.; Kohno, M. CHEMTECH 1984, 14, 670. (5) (a) Okuda, S. Japanese Patent No. 57158746, 1982; Chem. Abstr. 1983, 98, 144386b. (b) Okuda, S. Japanese Patent No. 57158747, 1982; Chem. Abstr. 1983, 99, 105872h. (6) Valli, V. L. K.; Alper, H. J. Org. Chem. 1995, 60, 257.
reaction of amines with carbon dioxide and dehydration of the resulting carbamate salt. The Monsanto group have reported the use of a range of oxophilic reagents, e.g. POCl3,7 to achieve in situ dehydration. The preparation of isocyanates by reaction of preformed phosphoruscontaining intermediates with carbon dioxide has been reported previously.8,9 Reactions of amines with carbon dioxide have also been used to prepare alkali metal carbamates10 and carbamate esters11 in high yield. A mild and rapid method for isocyanate synthesis involving (dimethylamino)pyridine-catalyzed reactions of di-tertbutyl dicarbonate, (Boc)2O, with sterically hindered arylamines has recently been reported together with detailed mechanistic studies.12 In this paper we describe a very mild method for the preparation of alkyl isocyanates from primary aliphatic amines and carbon dioxide using a Mitsunobu zwitterion generated from either diisopropyl azodicarboxylate (DIAD) or di-tert-butyl azodicarboxylate and triphenylphosphine or tri-n-butylphosphine.13 High yields of isocyanates from hindered aromatic amines can also be obtained but only when the zwitterion generated from Bu3P is used. Results and Discussion Reactions of Aliphatic Amines. Reactions of solutions of primary aliphatic amines 1 in dichloromethane with CO2 at -5 to -10 °C gave carbamate salts 2 which sometimes precipitated from solution. In a separate flask the Mitsunobu zwitterion 4 was prepared by addition of (7) Waldman, T. E.; McGhee, W. D. J. Chem. Soc., Chem. Commun. 1994, 957. (8) Molina, P.; Alajarin, M.; Arques, A. Synthesis 1982, 7, 596. (9) Wadsworth, W. S.; Emmons, W. D. J. Org. Chem. 1964, 29, 2816. (10) Aresta, M.; Dibendetto, A.; Quaranta, E. J. Chem. Soc., Dalton Trans. 1995, 3359. (11) McGhee, W. D.; Riley, D.; Christ, K.; Pan, Y.; Parnas, B. J. Org. Chem. 1995, 60, 2820. (12) Kno¨lker, H. J.; Braxmeier, T.; Schlectingen, G. Angew. Chem., Int. Ed. Engl. 1995, 34, 2497. (13) Camp, D.; Jenkins, I. D. Aust. J. Chem., 1992, 45, 47.
10.1021/jo982362j CCC: $18.00 © 1999 American Chemical Society Published on Web 05/07/1999
Isocyanates from Primary Amines and Carbon Dioxide
J. Org. Chem., Vol. 64, No. 11, 1999 3941 Table 1. Yields of Isocyanates 5 from Reactions of Amines 1 with CO2 and the Mitsunobu Zwitteriona
yield (%) of isocyanate (5) entry
amine (1) R
estimated by IR
isolated
1 2 3 4 5 6 7 8
i-Pr i-Pr n-Bu t-Bu cyclohexyl n-octyl tert-octylc 3R-cholestanyl
94 90b 76 95 90 69 93 89
86 63 84 80 65 87 86
diisopropyl azodicarboxylate (DIAD) to a solution of triphenylphosphine in dichloromethane at -20 °C. Both solutions were cooled to -78 °C, and the zwitterion solution was cannulated into the carbamate-containing solution. More carbon dioxide was passed into the solution after addition and the reaction mixture allowed to warm to ambient temperature and to stand overnight. Dichloromethane was added to achieve a standard volume and an IR spectrum of an aliquot taken. The intensity of the IR band due to the cumulated NdCdO stretch in the isocyanate (in the region 2269 ( 10 cm-1) was compared with those from standard solutions and an estimate of the yield of isocyanate prior to distillation obtained. The product was fractionally distilled first to remove dichloromethane and then to obtain an isolated yield of isocyanate. Yields of distilled products and estimated yields prior to distillation are given in Table 1. The yields of isocyanates in the reaction mixtures prior to distillation were all excellent for amines with secondary (entries 1 and 5) or tertiary (entries 4 and 7) alkyl substituents and still good for primary aliphatic amines (entries 3 and 6). The excellent recovery of isolated isocyanates testifies to the lack of adversely reactive byproducts, as the difficulties in isolating isocyanates are well established, e.g., leading to the formation of isocyanurates and uretidiones.14 The reactions were shown to be very fast. A reaction of isopropylamine was carried out in an NMR tube at -78 °C and the 31P spectrum monitored. The first spectrum recorded ca. 3 min after addition of isopropylamine-derived carbamate to a solution of the zwitterion iPrO C-N(Ph P+)-N--CO iPr showed no signal for the 2 3 2 zwitterion at 45.2 ppm but only a signal at 28.4 ppm due to Ph3PO. Accordingly, a reaction of isopropylamine was worked up immediately on warming to ambient temperature and shown to give isocyanate in a yield comparable to that obtained on standing overnight (entry 2). Reactions of n-octylamine, isopropylamine, and 3Rcholestanylamine with CO2 were carried out using the Mitsunobu zwitterion generated from DIAD and Bu3P. This zwitterion was generated and used at temperatures below -20 °C in order to avoid its decomposition,14 but otherwise reaction conditions were identical to those described above involving Ph3P. Comparable isolated yields were obtained, 60% for n-octylamine (cf. entry 6) 84% for isopropylamine (cf. entry 1) and 90% for the cholestanylamine (cf. entry 8). Reactions using the zwitterion generated from Ph3P and di-tert-butyl azodicarboxylate gave similar conversions to those summarized in Table 1 for reactions of n-butylamine (56% IR estimated yield, cf. entry 3) and tert-octylamine (90% IR estimated yield, cf. entry 7).
Thus, there is no advantage in using the relatively expensive di-tert-butyl azodicarboxylate nor the comparatively unstable zwitterion generated from DIAD and Bu3P over the Ph3P-DIAD-derived zwitterion for reactions of aliphatic amines. THF could also be used as a solvent and a reaction of tert-octylamine with CO2 and the Ph3P-generated zwitterion gave an excellent yield (quantitative by IR, 93% isolated). Two reactions were carried out in which the zwitterion was generated in THF and added to the amine in supercritical CO2. Only low yields (25-30%) of isocyanate were obtained, probably due to the very low solubility of the carbamate salt in the CO2/THF solvent mixture. Reactions of Aromatic Amines. High yields of isocyanates have been reported from reactions of hindered aromatic amines with di-tert-butyl dicarbonate.12 Lower yields of isocyanates were obtained when less sterically hindered arylamines were reacted due to further reaction of the isocyanates with simultaneously formed tert-butyl alcohol. Similarly, high yields of isocyanates were obtained from reactions of hindered arylamines including hindered diamines (entries 13 and 14) with CO2 and the Mitsunobu zwitterion generated from DIAD and Bu3P (see Table 2). All of the 2,6-disubstituted anilines gave isolated yields of isocyanates g 65% (entries 9-14). If, however, at least one of the substituents ortho to the amine is removed, the yield of isocyanate becomes negligible (entries 15 and 16). Yields of isocyanate were much lower (ca. 20%) when the Mitsunobu zwitterion derived from Ph3P in place of Bu3P was used in reactions of mesidine (entry 21) and 2,6-diisopropylaniline (entry 22) (Table 3). Reactions of mesidine using Ph3P and Bu3P were also carried out in an NMR tube at -78 °C and the 31P spectra monitored. The signal due to the zwitterion iPrO C-N(Bu P+)-N--CO iPr (67.5 ppm) disappeared 2 3 2 immediately the spectrum was recorded after mixing and was replaced by a signal at 53.1 ppm due to Bu3PO together with a very small signal at 76.9 ppm which disappeared on warming leaving only the signal due to Bu3PO (now 46.4 ppm at ambient temperature, lit.15 46.9 ppm). In contrast, the reaction involving the Ph3P-derived zwitterion was much slower, and the initial spectrum (ca.
(14) Schwetlick, K.; Noack, R. J. Chem. Soc., Perkin Trans. 2 1995, 395.
(15) Albright, T. A.; Freeman, W. J.; Schweizer, E. E. J. Org. Chem. 1975, 40, 3437.
a Reactions in dichloromethane from -78 °C to ambient temperature. Full conditions and isolation procedures are given in the text. b Reaction worked up immediately on reaching ambient temperature, ca. 3 h, IR yield only. c 2,4,4-Trimethyl-2-pentylamine.
3942 J. Org. Chem., Vol. 64, No. 11, 1999
Saylik et al.
Table 2. Yields of Isocyanates from Reactions of Hindered Aromatic Amines with CO2 and the Mitsunobu Zwitterion
yield (%) of isocyanate (5) entry
amine (1) R
estimated by IR
isolated
9 10 11 12 13 14 15 16
2,4,6-tri-MeC6H2 2,6-di-EtC6H3 2-Et-6-MeC6H3 2,6-di-iPrC6H3 2,4,6-trimethylbenzene-1,3-diamine 4,4′-methylenebis(2,6-dimethylaniline) 2-iPrC6H4 C6H5
100 80 77 100 68 84
