Chemical Sciences: A Manual for CSIR-UGC National Eligibility Test for Lectureship and JRF/Named Reactions/Curtius Rearrangement

The Curtius rearrangement (or Curtius reaction or Curtius degradation), as first defined by Theodor Curtius, is a chemical reaction that involves the rearrangement of an acyl azide to an isocyanate. Curtius, T. Ber. 1890 23 3023doi:10.1002/prac.18940500125 Several reviews have been published. Smith, P. A. S. Org. React. 1946 3 337–449doi:10.1021/cr00084a001 300px|The Curtius rearrangement The isocyanate can be trapped by a variety of nucleophiles. Often water is added to hydrolyze the isocyanate to an amine. Kaiser, C.; Weinstock, J. Amines from mixed carboxylic-carbonic anhydrides: 1-phenylcyclopentylamine 6 910 1988 cv6p0910 When done in the presence of tert-butanol, the reaction generates Boc-protected amines, useful intermediates in organic synthesis.doi:10.1021/op970115wdoi:10.1021/ol051428b Carboxylic acids 1 can be easily converted to acyl azides 3 using diphenylphosphoryl azide 2. Shioiri, T.; Yamada, S. Diphenyl phosphorazidate 7 206 1990 cv7p0206doi:10.1021/ja00772a052doi:10.1016/S0040-4020(01)97352-1 550px|Using DPPA to convert an acid to a BOC-protected amine Likewise, when the Curtius reaction is performed in the presence of benzyl alcohol, Cbz-protected amines are formed. 1-N-Acylamino-1,3-dienes from 2,4-pentadienoic acids by the Curtius rearrangement: benzyl trans-1,3-butadiene-1-carbamate Jessup, P. J.; Petty, C. B.; Roos, J.; Overman, L. E. 6 95 1988 cv6p0095 Reaction mechanism The first step of the Curtius rearrangement is the loss of nitrogen gas forming an acyl nitrene (2). Once formed, acyl nitrenes very quickly rearrange by migration of R-group forming the desired isocyanate (3). 600px|The mechanism of the Curtius rearrangement Scope In one variation called the Darapsky degradation (A. Darapsky, 1936) a Curtius rearrangement takes place as one of the steps from an α-cyanoester to an amino acid.http://www.chempensoftware.com/reactions/RXN051.htm References 2