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DOI: 10.1055/s-2007-990813
Preparation of Mono-, Di-, and Trisubstituted Ureas by Carbonylation of Aliphatic Amines with S,S-Dimethyl Dithiocarbonate
Publication History
Publication Date:
25 September 2007 (online)
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Abstract
General procedures are reported to prepare N-alkylureas, N,N′-dialkylureas (both symmetrical and unsymmetrical), and N,N,N′-trialkylureas by carbonylation of aliphatic amines, employing S,S-dimethyl dithiocarbonate (DMDTC) as a phosgene substitute. All reactions were carried out in water. Symmetrical disubstituted ureas were prepared directly working at 60 °C with a molar ratio of DMDTC:amine = 1:2, preferably under nitrogen. Unsymmetrical ureas were prepared in two steps via S-methyl N-alkylthiocarbamate intermediates, which are formed selectively in the first step at room temperature. These intermediates react in the second step with ammonia or various aliphatic amines, both primary and secondary, at temperatures varying between 50 and 70 °C. All the target ureas were obtained in high yields (28 examples, average yield 94%) and with very high purity (generally >99.2%). Also to be noted is the recovery of a co-product of industrial interest, methanethiol, in an amount of two moles for each mole of DMDTC, with complete exploitation of the reagent.
Key words
ureas - carbonylation - amines - dithiocarbonates - thiocarbamates
- For reviews on ureas, see:
-
2a
Sartori G.Maggi R. In Science of Synthesis Vol. 18:Knight JG. Thieme Verlag; Stuttgart: 2005. p.665-758 -
2b
Bigi F.Maggi R.Sartori G. Green Chem. 2000, 2: 140 -
2c
Tafesh AM.Weiguny J. Chem. Rev. 1996, 96: 2035 -
2d
Petersen H. In Ullmann’s Encyclopedia of Industrial Chemistry 5th ed., Vol. A27:Elvers B.Hawkins S. VCH; Weinheim: 1996. p.355-365 -
2e
Vishnyakova TP.Golubeva IA.Glebova EV. Russ. Chem. Rev. 1985, 54: 249 -
2f
Petersen U. In Houben-Weyl 4th ed., Vol. E4:Hagemann H. Thieme Verlag; Stuttgart: 1983. p.334-367 ; and references cited therein -
2g
Melnikov NN. In Chemistry of PesticidesGunther FA.Gunther JD. Springer-Verlag; Berlin: 1971. p.225-239 - 3 For a plentiful recent literature (until 2003) on the synthesis and applications of substituted ureas see:
Gabriele B.Salerno G.Mancuso R.Costa M. J. Org. Chem. 2004, 69: 4741 ; and references cited therein - Some recent references (after 2003) on new applications of substituted ureas:
-
4a
Martinez Gil A,Medina Padilla M,Castro Morera A,Alonso Cascon M,Martin Aparicio E,Fuertes Huerta A,Navarro Rico ML, andPerez Puerto MJ. inventors; Neuropharma S. A., Spain, EP 1749523. ; Chem. Abstr. 2007, 146, 206112 -
4b
Bhalay G,Dunstan A,Glen A,Howe TJ, andMcCarthy C. inventors; Novartis AG Switzerland, Novartis Pharma GmbH, WO 015852. 2006; Chem. Abstr. 2006, 144, 232805 -
4c
Dasseux J.-LH, andOniciu DC. inventors; Esperion Therapeutics Inc. USA, WO 068420. ; Chem. Abstr. 2005, 143, 172557 -
4d
Carruthers NI,Shah CR, andSwanson DM. inventors; Janssen Pharmaceutica, N. V., Belgium, WO 014580. ; Chem. Abstr. 2005, 142, 240468 -
4e
Defossa E,Kadereit D,Klabunde T,Burger H.-J,Herling A,Wendt K.-U,Von Roedern E,Schoenafinger K, andEnhsen A. inventors; Aventis Pharma Deutschland GmbH, Germany, WO 065356. ; Chem. Abstr. 2004, 141, 173980 - Some recent references (after 2003) on the use of monoalkyl-, dialkyl-, and trialkylureas in organic synthesis:
-
5a
Fritz JA.Nakhla JS.Wolfe JP. Org. Lett. 2006, 8: 2531 -
5b
Sigachev AS.Kravchenko AN.Gazieva GA.Belyakov PA.Kolotyrkina NG.Lebedev OV.Makhova NN.Lyssenko KA. J. Heterocycl. Chem. 2006, 43: 1295 -
5c
Gel’mbol’dt VO.Koroeva LV.Filinchuk Ya E. Russ. J. Coord. Chem. 2005, 31: 775 -
5d
Natarajan A.Guo Y.Arthanari H.Wagner G.Halperin JA.Chorev M. J. Org. Chem. 2005, 70: 6362 -
5e
Hansen AL.Skrydstrup T. J. Org. Chem. 2005, 70: 5997 -
5f
Kravchenko AN.Sigachev AS.Maksareva EY.Gazieva GA.Trunova NS.Lozhkin BV.Pivina TS.Il’in MM.Lyssenko KA.Nelyubina YV.Davankov VA.Lebedev OV.Makhova NN.Tartakovsky VA. Russ. Chem. Bull. 2005, 54: 691 -
5g
Zhou X,Chen Y, andLiu B. inventors; Faming Zhuanli Shenqing Gongkai Shuomingshu, CN 1515540 A. ; Chem. Abstr. 2005, 143, 77851 - Some recent references (after 2003) on the synthesis of monoalkyl-, dialkyl-, and trialkylureas:
-
6a
Peng X.Li F.Xia C. Synlett 2006, 1161 ; and references cited therein -
6b
Mizuno T.Mihara M.Iwai T.Ito T.Ishino Y. Synthesis 2006, 2825 ; and references cited therein -
6c
Zhu B.Angelici RJ. J. Am. Chem. Soc. 2006, 128: 14460 -
6d
Orito K.Miyazawa M.Nakamura T.Horibata A.Ushito H.Nagasaki H.Yuguchi M.Yamashita S.Yamazaki T.Tokuda M. J. Org. Chem. 2006, 71: 5951 ; and references cited therein -
6e
Fan X,Rui B,Yan L, andLi C. inventors; Faming Zhuanli Shenqing Gongkai Shuomingshu, CN 1827594 A. ; Chem. Abstr. 2006, 145, 397096 -
6f
Wang C,Li Y,Du M,Xu S,Zheng C,Wang C,Yang X,Shi L, andWang W. inventors; Faming Zhuanli Shenqing Gongkai Shuomingshu, CN 1740140 A. ; Chem. Abstr. 2006, 145, 10086 -
6g
Li Z.Wang Z.-Y.Zhu W.Xing Y.-L.Zhao Y.-L. Synth. Commun. 2005, 35: 2325 -
6h
Nishiyama Y.Kawamatsu H.Sonoda N. J. Org. Chem. 2005, 70: 2551 -
6i
Perveen S.Abdul Hai SM.Khan RA.Khan KM.Afza N.Sarfaraz TB. Synth. Commun. 2005, 35: 1663 -
6j
Enquist P.-A.Nilsson P.Edin J.Larhed M. Tetrahedron Lett. 2005, 46: 3335 -
6k
Fujita S.Bhanage BM.Kanamaru H.Arai M. J. Mol. Catal. A: Chem. 2005, 230: 43 ; and references cited therein -
6l
Pourali AR. Monatsh. Chem. 2005, 136: 733 -
6m
Grzyb JA.Shen M.Yoshina-Ishii C.Chi W.Brown RS.Batey RA. Tetrahedron 2005, 61: 7153 -
6n
Yang C. inventors; Faming Zhuanli Shenqing Gongkai Shuomingshu, CN 1660795 A. ; Chem. Abstr. 2006, 144, 469979 -
6o
Hiwatari K.Kayaki Y.Okita K.Ukai T.Shimizu I.Yamamoto A. Bull. Chem. Soc. Jpn. 2004, 77: 2237 -
6p
Zhang Q.Shi F.Deng Y. Cuihua Xuebao 2004, 25: 607 ; Chem. Abstr. 2005, 142, 373529 -
6q
Fujita S.Bhanage BM.Arai M. Chem. Lett. 2004, 742 ; Chem. Abstr. 2004, 141, 156829 -
6r
Qian WX.Ju FY.Zhang YM.Bao WL. Chin. Chem. Lett. 2004, 15: 1269 ; Chem. Abstr. 2005, 142, 155314 -
6s
Porwanski S.Menuel S.Marsura X.Marsura A. Tetrahedron Lett. 2004, 45: 5027 - 7
Degani I.Fochi R.Regondi V. Synthesis 1981, 149 -
9a
Degani I,Fochi R, andRegondi V. inventors; CNR, Italy, Eur. Pat. Appl. 63327. ; Chem. Abstr. 1983, 98: 160238 -
9b
Degani I.Fochi R.Regondi V. Synthesis 1983, 630 -
9c
Degani I.Fochi R.Regondi V. Synthesis 1986, 1070 -
9d
Degani I,Fochi R, andRegondi V. inventors; CNR, Italy, IT 1173436. - 10
Cadamuro S.Degani I.Fochi R.Regondi V. Chem. Ind. (London) 1986, 671 -
11a
Barbero M,Degani I,Fochi R, andRegondi V. inventors; CNR, Italy, Eur. Pat. Appl. 234249. ; Chem. Abstr. 1988, 108, 23697 -
11b
Barbero M.Cadamuro S.Degani I.Fochi R.Regondi V. Synthesis 1989, 857 - 12
Leung M.-kit.Lai J.-L.Lau K.-H.Yu H.-hua.Hsiao H.-J. J. Org. Chem. 1996, 61: 4175 - 13
Carvoli G,Degani I,Pallucca E,Fochi R,Serri AM,Cadamuro S,Gazzetto S, andMigliaccio M. inventors; Oxon Italia S.p.A., Italy, MI 2004A 002402. IT patent pending: patent request No.(16.12.2004) - 14
Artuso E.Carvoli G.Degani I.Fochi R.Magistris C. Synthesis 2007, 1096 - For example, for toxicity of phosgene, see:
-
15a
Sax NI. In Dangerous Properties of Industrial Materials Van Nostrand Reinhold Company; New York: 1984. p.2210-2211 -
15b
Senet J.-P. In The Recent Advance in Phosgene Chemistry Vol. 1: GPA; Nanterre: 1997. p.10-11 -
15c
Cotarca L.Eckert H. In Phosgenations - A Handbook Wiley-VCH; Weinheim: 2003. p.9 - 16
Carvoli G,Degani I,Pallucca E,Fochi R,Gazzetto S,Artuso E,Lazzaroni M, andCadamuro S. inventors; Oxon Italia S.p.A., Italy, MI 2005A 001284. Details are reported in an IT patent pending: patent request No.(07.07.2005) - 17 Dictionary of Organic Compounds on CD-ROM Chapman & Hall, Electronic Publishing Division; London: 2007. Version 15.1 [CD ROM]
-
18a
Atanassova IA.Petrov JS.Mollov NM. Synth. Commun. 1989, 19: 147 -
18b
Hayashi T.Kuyama M. Nat. Sci. Rep. Ochanomizu Univ. (Tokyo) 1951, 2: 79 ; Chem. Abstr. 1954, 48, 1274b - 19
Bakibaev AA. Russ. J. Org. Chem. 1994, 30: 1772 - 20
Troyanskii EA.Ioffe VA.Mizintsev VV.Nikishin GI. Bull. Acad. Sci. USSR 1984, 33: 1661 - 21
Lutsenko VV.Blyum RA.Knunyants IL. J. Chem. Org. USSR 1971, 7: 1182 - 22
Martinelli LC.DeWitt Blauton C.Whidby JF. J. Am. Chem. Soc. 1971, 93: 5111 - 23
Kim HO.Ji X.Melman N.Olah ME.Stiles GL.Jacobson KA. J. Med. Chem. 1994, 37: 3373 - 24
Wiloth F.Schindler E. Chem. Ber. 1970, 103: 757 - 25
Nowick JS.Abdi M.Bellamo KA.Love JA.Martinez EJ.Noronha G.Smith EM.Ziller JW. J. Am. Chem. Soc. 1995, 117: 89 - 27
McCusker JE.Main AD.Johnson KS.Grasso CA.McElwee-White L. J. Org. Chem. 2000, 65: 5216 -
28a
Kochansky JP.Feldmesser J. J. Nematol. 1989, 21: 158 -
28b
Kochansky JP.Feldmesser J. J. Econ. Entomol. 1985, 78: 599 - 29
Rouzer CA.Sabourin M.Skinner TL.Thompson EJ.Wood TO.Chmurny GN.Klose JR.Roman JM.Smith RH.Michejda CJ. Chem. Res. Toxicol. 1996, 9: 172 - 30
Pallucca E,Degani I,Serri AM,Fochi R,Gazzetto S,Fenoglio C,Ornati C,Migliaccio M,Cadamuro S, andCarvoli G. inventors; Oxon Italia S.p.A., Italy, EP 1334965. ; Chem. Abstr. 2003, 139, 164529
References
Professor Emeritus, University of Turin, Italy.
8Oxon Italia S.p.A. (Italy).
26Spectral Data Base for Organic Compounds SDBS (National Institute of Advanced Industrial Science and Technology). SDBS Web: http://www.aist.go.jp/RIODB/SDBS.