The Curtius rearrangement (or Curtius reaction or Curtius degradation), as first defined by Theodor Curtius

Theodor Curtius

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, is a chemical reaction

Chemical reaction

A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...

 that involves the rearrangement of an acyl azide to an isocyanate

Isocyanate

Isocyanate is the functional group of elements –N=C=O , not to be confused with the cyanate functional group which is arranged as –O–C≡N or with isocyanide, R-N≡C. Any organic compound which contains an isocyanate group may also be referred to in brief as an isocyanate. An isocyanate may have more...

. Several reviews have been published.

The isocyanate can be trapped by a variety of nucleophile

Nucleophile

A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...

s. Water is often added in order to hydrolyze the isocyanate to an amine

Amine

Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...

. When done in the presence of tert-butanol

Tert-Butanol

tert-Butanol, or 2-methyl-2-propanol, is the simplest tertiary alcohol. It is one of the four isomers of butanol. tert-Butanol is a clear liquid with a camphor-like odor. It is very soluble in water and miscible with ethanol and diethyl ether...

, the reaction generates Boc-protected

Protecting group

A protecting group or protective group is introduced into a molecule by chemical modification of a functional group in order to obtain chemoselectivity in a subsequent chemical reaction...

 amines, useful intermediates in organic synthesis

Organic synthesis

Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...

.

Carboxylic acid

Carboxylic acid

Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...

s 1 can be easily converted to acyl azides 3 using diphenylphosphoryl azide

Diphenylphosphoryl azide

Diphenylphosphoryl azide is an organic compound. It is widely used in synthesis of other organic compounds.-Synthesis:...

 2.

Likewise, when the Curtius reaction is performed in the presence of benzyl alcohol

Benzyl alcohol

Benzyl alcohol is an organic compound with the formula C6H5CH2OH. The benzyl group is often abbreviated "Bn", thus benzyl alcohol is denoted as BnOH. Benzyl alcohol is a colorless liquid with a mild pleasant aromatic odor. It is a useful solvent due to its polarity, low toxicity, and low vapor...

, Cbz

Carboxybenzyl

Carboxybenzyl or Cbz or Z is an amine protecting group in organic synthesis. It is commonly used in peptide synthesis and is formed by reacting an amine with benzyl chloroformate and a weak base:It is used to protect amines from electrophiles...

-protected amines are formed.

Reaction mechanism

The Curtius rearrangement may be thought of as a two-step process, the first step being the loss of nitrogen

Nitrogen

Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...

 gas, forming an acyl nitrene (2), and the second step being the rearrangement of acyl nitrenes by migration of R-group to form the desired isocyanate

Isocyanate

Isocyanate is the functional group of elements –N=C=O , not to be confused with the cyanate functional group which is arranged as –O–C≡N or with isocyanide, R-N≡C. Any organic compound which contains an isocyanate group may also be referred to in brief as an isocyanate. An isocyanate may have more...

 (3). However, current evidence indicates that these two steps are likely concerted (i.e., they occur at the same time), and no free nitrene intermediate is formed.

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

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

.

See also

• Beckmann rearrangement
  Beckmann rearrangement
  The Beckmann rearrangement, named after the German chemist Ernst Otto Beckmann , is an acid-catalyzed rearrangement of an oxime to an amide...
  
  
• Hofmann rearrangement
  Hofmann rearrangement
  The Hofmann rearrangement is the organic reaction of a primary amide to a primary amine with one fewer carbon atom.The reaction is named after its discoverer: August Wilhelm von Hofmann...
  
  
• Lossen rearrangement
  Lossen rearrangement
  The Lossen rearrangement is the conversion of a hydroxamic acid to an isocyanate via the formation of an O-acyl, sulfonyl, or phosphoryl intermediate hydroxamic acid O-derivative and then conversion to its conjugate base. Here, 4-Toluenesulfonyl chloride is used to form a sulfonyl O-derivative...
  
  
• Schmidt reaction
  Schmidt reaction
  The Schmidt reaction is an organic reaction involving alkyl migration over the carbon-nitrogen chemical bond in an azide with expulsion of nitrogen...
  
  
• Tiemann rearrangement
• Wolff rearrangement
  Wolff rearrangement
  The Wolff rearrangement is a rearrangement reaction converting a α-diazo-ketone into a ketene. This reaction was first reported by Ludwig Wolff in 1912....