Categories: C-N Bond Formation >
Synthesis of urea derivatives
General procedures allow the carbonylation of aliphatic amines by employing S,S-dimethyl dithiocarbonate (DMDTC) as a phosgene substitute to yield N-alkylureas, N,N′-dialkylureas (both symmetrical and unsymmetrical), and N,N,N′-trialkylureas. All reactions were carried out in water.
E. Artuso, I. Degani, R. Fochi, C. Magistris, Synthesis, 2007, 3497-3506.
A one pot reaction of carbonylimidazolide in water with a nucleophile provides an efficient and general method for the preparation of urea, carbamates and thiocarbamates without an inert atmosphere. Products precipitate out from the reaction mixture and can be obtained in high purity by filtration.
K. J. Padiya, S. Gavade, B. Kardile, M. Tiwari, S. Bajare, M. Mane, V. Gaware, S. Varghese, D. Harel, S. Kurhade, Org. Lett., 2012, 14, 2814-2817.
With ambient pressure of carbon monoxide and oxygen at room temperature, N,N-dialkyl-N′-arylureas were selectively accessible from secondary amines, aromatic amines, and sulfur in very good yields.
T. Mizuno, T. Nakai, M. Mihara, Synthesis, 2009, 2492-2496.
Hydroxamic acids were synthesized from carboxylic acids and hydroxylamine hydrochloride in the presence of ethyl 2-cyano-2-(4-nitrophenylsulfonyloxyimino)acetate (4-NBsOXY). 4-NBsOXY also promotes the Lossen rearrangement of hydroxamic acids in the presence of amines to yield ureas. The reactions are compatible with common N- and O-protecting groups and prevent racemization.
K. Thalluri, S. R. Manne, D. Dev, B. Mandal, J. Org. Chem., 2014, 79, 3765-3775.
An efficient method for palladium-catalyzed cross-coupling of aryl chlorides and triflates with sodium cyanate allows the synthesis of unsymmetrical N,N′-di- and N,N,N′-trisubstituted ureas in one pot and is tolerant of a wide range of functional groups. Insight into the mechanism of aryl isocyanate formation was gleaned through studies of the transmetalation and reductive elimination steps of the reaction.
E. V. Vinogradova, B. P. Fors, S. L. Buchwald, J. Am. Chem. Soc., 2012, 134, 11132-11135.
1-Propanephosphonic acid cyclic anhydride (T3P) promotes the synthesis of hydroxamic acids from carboxylic acids. Application of ultrasonication accelerates this conversion. Further, T3P has also been employed to activate the hydroxamates, leading to isocyanates via Lossen rearrangement. Trapping with suitable nucleophiles affords the corresponding ureas and carbamates.
B. Vasantha, H. P. Hemantha, V. V. Sureshbabu, Synthesis, 2010, 2990-2996.
Carbonyldiimidazole mediates the Lossen rearrangement of various hydroxamic acids to isocyanates. This process is experimentally simple and mild, with imidazole and CO2 being the sole stoichiometric byproduct. The method avoids the use of hazardous reagents and thus represents a green alternative to standard processing conditions for the Curtius and Hofmann rearrangements.
P. Dubé, N. F. F. Nathel, M. Vetelino, M. Couturier, C. L. Abossafy, S. Pichette, M. L. Jorgensen, M. Hardink, Org. Lett., 2009, 11, 5622-5625.
A smooth and efficient oxidation of isonitriles to isocyanates by DMSO as the oxidant is catalyzed by trifluoroacetic anhydride. The process is complete in a few minutes, forming dimethyl sulfide as the only byproduct. The newly formed isocyanates may be used directly or isolated in high purity by solvent evaporation.
H. V. Le, B. Ganem, Org. Lett., 2011, 13, 2584-2585.
Zirconium(IV)-catalyzed exchange processes of dialkyl carbonates and carbamates in the presence of amines gave carbamates and ureas using 2-hydroxypyridine (HYP) and 4-methyl-2-hydroxyquinoline (MeHYQ) as catalytic additives, respectively. A microwave acceleration effect was observed in Zr(IV)-catalyzed carbamate-urea exchange.
C. Han, J. A. Porco, Jr, Org. Lett., 2007, 9, 1517-1520.
Selective and convenient syntheses of carbamates, symmetric ureas, and unsymmetrical ureas have been accomplished by the reaction of amines with phenyl 4,5-dichloro-6-oxopyridazine-1(6H)-carboxylate as a carbonyl source under mild conditions.
H.-G. Lee, M.-J. Kim, S.-E. Park, J.-J. Kim, S.-G. Lee, Y.-J. Yoon, Synlett, 2009, 2809-2814.
A facile one-pot procedure for the synthesis of urea-linked peptidomimetics and neoglycopeptides under Curtius rearrangement conditions employing Deoxo-Fluor and TMSN3 is efficient and circumvents the isolation of acyl azide and isocyanate intermediates. The reaction was carried out under ultrasonication.
H. P. Hemantha, G. Chennakrishnareddy, T. M. Vishwanatha, V. V. Sureshbabu, Synlett, 2009, 407-410.
The reaction of di-tert-butyl dicarbonate or a chloroformate and sodium azide with an aromatic carboxylic acid produces the corresponding acyl azide. The acyl azide undergoes a Curtius rearrangement to form an isocyanate derivative which is trapped either by an alkoxide or by an amine to form the aromatic carbamate or urea.
H. Lebel, O. Leogane, Org. Lett., 2006, 8, 5717-5720.
Readily prepared carbamoylimidazolium salts act as efficient N,N-disubstituted carbamoylating reagents, as a result of the ‘imidazolium’ effect. The salts react with amines, thiols, phenols/alcohols, and carboxylic acids in high yields, without the need for subsequent chromatographic purification of the products, producing ureas, thiocarbamates, carbamates, and amides, respectively.
M. B. Bertrand, J. P. Wolfe, Tetrahedron, 2005, 61, 6447-6459.
High-yielding reductive alkylation of electron-deficient o-haloarylamines followed by treatment with inexpensive N-chlorosulfonyl isocyanate afforded primary ureas in good overall yields. A Pd-catalyzed urea cyclization reaction furnished imidazopyridinones and benzoimidazolones in excellent yields.
M. McLaughlin, M. Palucki, I. W. Davies, Org. Lett., 2006, 8, 3311-3314.
Imidazolidin-2-ones are prepared in two steps from readily available N-allylamines. Addition of the amine starting materials to isocyanates affords N-allylureas, which are converted to imidazolidin-2-ones with generation of two bonds and up to two stereocenters in the presence of aryl bromides, a catalytic amount of Pd2(dba)3/Xantphos and NaOtBu.
J. A. Fritz, J. S. Nakhla, J. P. Wolfe, Org. Lett., 2006, 8, 2531-2534.
Aliphatic and aromatic aldehydes can be converted to acyl azides by treatment with iodine azide. If the reaction is performed at reflux, Curtius rearrangement occurs and carbamoyl azides are obtained directly from the aldehyde in good yield.
L. Marinescu, J. Thinggaard, I. B. Thomsen, M. Bols, J. Org. Chem., 2003, 68, 9453-9455.
The reaction of carbamoyl azides with hydroxylamine leads to N-hydroxyureas, whereas the reaction of carbamoyl cyanides with hydroxylamine gives carbamoyl amidoxime derivatives. The latter type of compound represents an interesting precursor for heterocyclic structures.
J. Paz, C. Pérez-Balado, B. Iglesias, L. Muñoz, J. Org. Chem., 2010, 75, 8039-8047.
Carbamates can be converted into ureas using aluminum amide complexes. Bi-, tri- and tetra-substituted ureas were prepared from carbamate-protected primary or secondary amines by reaction with primary or secondary amines in the presence of stoichiometric quantities of trimethylaluminum.
S.-H. Lee, H. Matsushita, B. Clapham, K. D. Janda, Tetrahedron, 2004, 60, 3439-3443.