Curtius reaction

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Theodor Curtius (1857-1928)

The Curtius reaction (also Curtius degradation or Curtius rearrangement ) is a name reaction from the field of organic chemistry . It occurs when carboxylic acid azides R – CO – N 3 are heated and is closely related to Lossen degradation , Hofmann amide degradation and the Schmidt reaction . The reaction is mainly used to break down carboxylic acids to primary amines , but isocyanates , carbamates or urea derivatives can also be obtained depending on the reaction conditions. The reaction is named after its discoverer, the German chemist Theodor Curtius (1857–1928).

Overview

Overview reaction

The Curtius reaction converts a carboxylic acid azide to the primary amine via the intermediate stage of the isocyanate with water. The amine represented in this way is one carbon atom shorter than the carboxylic acid azide used, which is why it is also known as Curtius degradation :

Overview reaction of the Curtius degradation

Instead of water, the Curtius reaction can also take place with other nucleophiles . Reaction with an alcohol (R 2 OH) produces a carbamate, with an amine (R 2 NH 2 ) a derivative of urea:

Curtius reaction with other nucleophiles

If the Curtius rearrangement is carried out in the presence of tert- butanol , butyloxycarbonyl- (Boc) -protected amines are obtained and, in the presence of benzyl alcohol , the benzyloxycarbonyl- (Cbz) -protected amines are obtained accordingly.

Representation of the carboxylic acid azide

The carboxylic acid azides required as educt for the Curtius reaction are mostly synthesized from carboxylic acids or carboxylic acid derivatives ( carboxylic acid chlorides or carboxylic acid hydrazides ). Alternatively, carboxylic acid azides can be obtained by reacting the carboxylic acid with diphenylphosphoryl azide or with ethyl chloroformate via a mixed anhydride.

Reaction mechanism

When heat is applied, the carboxylic acid azide 1 is rearranged to form isocyanate 2 in a concerted reaction . In the process, molecular nitrogen is released. The nitrenes , often formulated as short-lived intermediates, are unlikely to occur. When carried out in an inert solvent, the isocyanates remain the end product of the reaction, while they continue to react in the presence of water to give the corresponding carbamic acid 3 , which decarboxylates immediately and gives the primary amine 4 as the end product .

Reaction mechanism of Curtius degradation

The reaction of isocyanate 2 with alcohols or amines takes place analogously to the formation of carbamic acid 3 . Reaction with tert- butanol produces a Boc-protected amine 5 :

Curtius reaction to produce a Boc-protected amine

literature

  • Peter AS Smith: The Curtius Reaction. In: Organic Reactions. 3, No. 9, 1946, pp. 337-449, doi : 10.1002 / 0471264180.or003.09 .
  • Eric FV Scriven, Kenneth Turnbull: Azides: their preparation and synthetic uses. In: Chemical Reviews. 88, No. 2, 1988, pp. 297-368, doi : 10.1021 / cr00084a001 .

Individual evidence

  1. ^ Th. Curtius: About hydrazoic acid (azoimide) N3H. In: Reports of the German Chemical Society. 23, No. 2, 1890, pp. 3023-3033, doi : 10.1002 / cber.189002302232 .
  2. ^ Th. Curtius: 20. Hydrazides and azides of organic acids I. Treatise. In: Journal for Practical Chemistry. 50, No. 1, 1894, pp. 275-294, doi : 10.1002 / prac.18940500125 .
  3. ↑ a b c László Kürti , Barbara Czakó: Strategic Applications of Named Reactions in Organic Synthesis . Elsevier Academic Press, Burlington / San Diego / London 2005, ISBN 0-12-369483-3 .
  4. ^ Kaiser, C .; Weinstock, J .: Amines from mixed carboxylic-carbonic anhydrides: 1-phenylcyclopentylamine In: Organic Syntheses . 51, 1971, p. 48, doi : 10.15227 / orgsyn.051.0048 ; Coll. Vol. 6, 1988, p. 910 ( PDF ).
  5. ↑ a b Reinhard Brückner: reaction mechanisms. 3rd edition, Springer Spectrum, Berlin and Heidelberg 2004. pp. 623–626, ISBN 978-3-662-45683-5 .
  6. ↑ Hélène Lebel, Olivier Leogane: Boc-Protected Amines via a Mild and Efficient One-Pot Curtius Rearrangement. In: Organic Letters. 7, No. 19, 2005, pp. 4107-4110, doi : 10.1021 / ol051428b .
  7. ^ Siegfried Hauptmann : Organic Chemistry , 2nd revised edition, VEB Deutscher Verlag für Grundstoffindindustrie, Leipzig, 1985, pp. 416 and 426, ISBN 3-342-00280-8 .
  8. ↑ Shioiri, T .; Yamada, S .: Diphenyl phosphorazidate In: Organic Syntheses . 62, 1984, p. 187, doi : 10.15227 / orgsyn.062.0187 ; Coll. Vol. 7, 1990, p. 206 ( PDF ).
  9. ↑ Takayuki Shioiri, Kunihiro Ninomiya, Shunichi Yamada: Diphenylphosphoryl azide. New convenient reagent for a modified Curtius reaction and for peptide synthesis. In: Journal of the American Chemical Society. 94, No. 17, 1972, pp. 6203-6205, doi : 10.1021 / ja00772a052 .
  10. ↑ K. Ninomiya, T. Shioiri, S. Yamada: Phosphorus in organic synthesis-VII: Diphenyl phosphorazidate (DPPA). A new convenient reagent for a modified curtius reaction. In: Tetrahedron. 30, No. 14, 1974, pp. 2151-2157, doi : 10.1016 / S0040-4020 (01) 97352-1 .
  11. ↑ Peter Sykes: Reaction Mechanisms - An Introduction. 8th edition, VCH, Weinheim 1982, ISBN 3-527-21090-3 , p. 140.