Nitrenes

Dr. Rangappa S. Keri

Associate Professor & Group Leader
Organic Chemistry & Drug Discovery Lab
Centre for Nano and Material Sciences
Jain University,
Jain Global Campus, Bangalore
 Syllabus

Nitrenes

a) Structure,

b) Formation,

c) Stability,

d) Detection and reactions of nitrenes

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 Definition Nitrene
s
 Nitrenes are uncharged, electron-deficient molecular fragments containing a
nitrogen atom with only six electrons in its valence shell (5,6). i.e sextet.

 The nitrogen analogous of carbenes are called nitrenes.

 Like carbenes, the nitrenes also exist in singlet and triplet states.

There is possibility of two spin states for nitrenes depending on whether the two
non-bonding electrons (the normal nitrogen lone pair remains paired) have their spins
paired or parallel.

 Both a singlet state, with two pairs of electrons and a low energy empty orbital,
and a triplet state, with one electron pair and two electrons with parallel spins, are
possible.

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 The singlet nitrenes are electrophilic while the triplet nitrenes behave as radicals.

 Nitrenes are very reactive species and cannot be isolated. However, a nitrene has been
trapped by its reaction with CO to yield an isocyanate.

 Nitrenes can also trapped in presence of ethylene.

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 Generation of nitrenes
a) From azides
Thermal or photolytic decomposition of azides give nitrenes.

• This is the most common method for the generation of nitrenes.

• Acyl and alkyl nitrenes can also be obtained by the photolysis of acyl azides and
isocyanates, respectively.

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 b) From sulfinylamines

Pyrolysis of sulfinylamines generates nitrenes.

sulfinylamines nitrene

c) From N-benzesulfonoxy carbamates

The reaction N-benzesulfonoxy carbamates with base, results in the formation

of carboalkoxynitrene with the elimination of benzenesulfonate anion.

N-benzesulfonoxy carbamates carboalkoxynitrene benzenesulfonate anion

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d) From Ylides
Photolytic decomposition of ylides give nitrenes.

ylides nitrenes

e) From Hetrocycles
Photolytic or thermal decomposition of some heterocycles give nitrenes.

f) From α-elimination
Nitrenes are formed after the α-elimination.

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g) From reduction of nitro or nitroso compounds
Nitrenes are formed after reduction of the nitro or nitroso compounds using pH reagents.

h) From oxidation of amine compounds

Nitrenes are formed after oxidation of amine compounds.

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Overall generation

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 Reactions of nitrenes
a) Addition to C=C bonds
Like carbenes, the addition of nitrenes to C=C bond is stereospecific with singlet and non-
stereospecific with triplet nitrene.

b) Insertion
Nitrene, particularly acyl nitrenes and sulfonyl nitrenes can insert into C-H
bonds.

Nitrene can also undergo insertion into C-H single bonds leading to ring closure. Thus, vinyl
azidothiophenes have found to be useful precursors for annulation of pyrroles and thiophene.

vinyl azidothiophenes annulation of pyrroles and thiophene

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 c) Dimerization
Like carbenes, nitrene also undergo dimerization reaction. Ex- aryl nitrenes give azobenzene.

aryl nitrenes azobenzene

d) Hydrogen abstraction
• Hydrogen abstraction from the carbon α to the nitrogen leads to the formation of imines.
• This process is of considerable synthetic importance.
• When hydrogen abstraction takes place from 4- and 5- position which is followed by ring
closure, the product formed are pyrrolidines and piperidines, respectively.

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e) Rearrangement reactions

Alkyl nitrenes do not generally give either of the two preceding reactions because
rearrangement is more rapid.
Example

Some name reaction involving nitrene as intermediate

a)Hofmann rearrangement
b)Curtius Rearrangement
c)Schmidt reaction
d)Lossen rearrangement
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Application

Some name reaction involving nitrene as intermediate

a)Hofmann rearrangement
b)Curtius Rearrangement
c)Schmidt reaction
d)Lossen rearrangement

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 a) Hofmann rearrangement
Conversion of primary amide to a primary amine with one fewer carbon atoms

Mechanism

1) Base abstracts an acidic N-H proton, yielding an anion.

2) The anion reacts with bromine in an α-substitution reaction to give an N-bromoamide.
3) Base abstraction of the remaining amide proton gives a bromoamide anion.
4) The bromoamide anion rearranges as the R group attached to the carbonyl carbon migrates to nitrogen
at the same time the bromide ion leaves, giving an isocyanate.
5) The isocyanate adds water in a nucleophilic addition step to yield a carbamic acid.
6) The carbamic acid spontaneously loses CO2, yielding the amine product.
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 b) Curtius rearrangement
Involves the rearrangement of an acyl azide to an isocyanate

Mechanism

It is two-step process.
1) In the first step being the loss of nitrogen gas, forming an acyl nitrene (2),
2) The second step being the rearrangement of acyl nitrenes by migration of R-
group to form the desired isocyanate (3).

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 Question from nitrenes
1) What are nitrenes? Explain with examples. (2)

2) What are nitrenes and explain their structure. (4)

3) Give any four methods of formation/generation of nitrenes (4)

4) Write the product

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