Curtius Rearrangement

The Curtius Rearrangement is the thermal decomposition of carboxylic azides to produce an isocyanate. These intermediates may be isolated, or their corresponding reaction or hydrolysis products may be obtained.

The reaction sequence - including subsequent reaction with water which leads to amines - is named the Curtius Reaction. This reaction is similar to the Schmidt Reaction with acids, differing in that the acyl azide in the present case is prepared from the acyl halide and an azide salt.

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Mechanism of the Curtius Rearrangement

Preparation of azides:

Decomposition:

Reaction with water to the unstable carbamic acid derivative which will undergo spontaneous decarboxylation:

Isocyanates are versatile starting materials:

Isocyanates are also of high interest as monomers for polymerization work and in the derivatisation of biomacromolecules.

Recent Literature

Propylphosphonic Anhydride (T3P®)-Mediated One-Pot Rearrangement of Carboxylic Acids to Carbamates
J. K. Augustine, A. Bombrun, A. B. Mandal, P. Alagarsamy, R. N. Atta, P. Selvam, Synthesis, 2011, 1477-1483.

Boc-Protected Amines via a Mild and Efficient One-Pot Curtius Rearrangement
H. Lebel, O. Leogane, Org. Lett., 2005, 7, 4107-4110.

DMAP Catalyzed One-Pot Curtius Rearrangement Using 1,1-Dimethyl-2,2,2-trichloroethoxycarbonyl Azide
K. Lin, H. Lu, Org. Lett., 2023, 25, 4534-4539.

An Improved Synthesis of Urea Derivatives from N-Acylbenzotriazole via Curtius Rearrangement
A. S. Singh, A. K. Agrahari, S. K. Singh, M. S. Yadav, V. K. Tiwari, Synthesis, 2019, 51, 3443-3450.

One-Pot Synthesis of Ureido Peptides and Urea-Tethered Glycosylated Amino Acids Employing Deoxo-Fluor and TMSN₃
H. P. Hemantha, G. Chennakrishnareddy, T. M. Vishwanatha, V. V. Sureshbabu, Synlett, 2009, 407-410.

N-Acylbenzotriazoles as Proficient Substrates for an Easy Access to Ureas, Acylureas, Carbamates, and Thiocarbamates via Curtius Rearrangement Using Diphenylphosphoryl Azide (DPPA) as Azide Donor
M. S. Yadav, S. K. Singh, A. K. Agrahari, A. S. Singh, V. K. Tiwari, Synthesis, 2021, 53, 2494-2502.

Radical Azidonation of Aldehydes
L. Marinescu, J. Thinggaard, I. B. Thomsen, M. Bols, J. Org. Chem., 2003, 68, 9453-9455.

Iodobenzene Dichloride in Combination with Sodium Azide for the Effective Synthesis of Carbamoyl Azides from Aldehydes
X.-Q. Li, X.-F. Zhao, C. Zhang, Synthesis, 2008, 2589-2593.

Radical Azidonation of Aldehydes
L. Marinescu, J. Thinggaard, I. B. Thomsen, M. Bols, J. Org. Chem., 2003, 68, 9453-9455.

Synthesis of Carbamoyl Azides from Redox-Active Esters and TMSN₃
X. Yuan, Y. Qu, Y. Li, H. Bao, Synlett, 2024, 35, 464-468.

An Efficient Synthesis of a Probe for Protein Function: 2,3-Diaminopropionic Acid with Orthogonal Protecting Groups
E. A. Englund, H. N. Gopi, D. H. Appella, Org. Lett., 2004, 6, 213-215.

Palladium-Catalyzed Cascade Carbonylative Synthesis of 1,2,4-Triazol-3-ones from Hydrazonoyl Chlorides and NaN₃
S. Du, W.-F. Wang, Y. Song, Z. Chen, X.-F. Wu, Org. Lett., 2021, 23, 974-978.