Product Class 13: 1,2,3-Triazoles

with CH 2Cl 2 afforded a crystalline crude product that was recrystallized (CCl 4); yield:
1.15 g (72%); mp 1228C.
13.13.1.1.3 By Formation of Two N-C Bonds
13.13.1.1.3.1 Fragments N-N-N and C-C
The most important and general approach to the synthesis of the 1,2,3-triazole ring system
involves azides. A wide variety of azides (organic or inorganic) can be used: alkyl,
aryl, hetaryl, acyl, alkoxycarbonyl and sulfonyl azides, azidotrimethylsilane, hydrazoic
acid, sodium azide, etc. All are suitable reagents for triazole synthesis.
Azides react with various types of compounds to yield 1,2,3-triazoles or their immediate
precursors. The most used are: (i) compounds with C”C bonds (here referred to as
alkynes, irrespectively of other functional groups), (ii) compounds with C=C bonds (here
referred to as alkenes, and including allenes, enamines, enol ethers, etc.), and (iii) activated
methylene compounds.
In spite of the great usefulness of the azides in the triazole synthesis, if the reaction
conditions (especially the temperature) are not well controlled, the products obtained
may be not the expected triazoles. This is because of the thermal instability of the azides
and of some of the intermediates (dihydrotriazoles) formed during the triazole synthesis.
[75] It is very important to always consider that most organic azides undergo thermal
or photochemical decomposition to nitrenes. The decomposition temperature is dependent
on the azide type (Table 2) and some azides, especially cyanogen azide and the lower
alkyl azides, are unpredictably explosive. When the decomposition is carried out in the
presence of an alkene the corresponding aziridine is usually obtained. [75]
Table 2 Decomposition Temperature of Azides [76]
Azide Type Decomposition Temp (8C) Ref
alkyl azides 180–200 [76]
aryl azides 140–170 [76]
sulfonyl azides 120–150 [76]
alkoxycarbonyl azides 100–130
[76]
acyl azides 25–80 [76]
13.13.1.1.3.1.1 Addition of Azides to Alkynes
FOR PERSONAL USE ONLY
438 Science of Synthesis 13.13 1,2,3-Triazoles
The thermal 1,3-dipolar cycloaddition of azides to alkynes is often the method of choice
for the synthesis of 1,2,3-triazoles since it gives directly the desired product. However,
when unsymmetrical alkynes are used, mixtures of the two possible regioisomers are
usually obtained. In general, addition to unsymmetrical alkynes tends to give mainly the
isomers with the electron-withdrawing groups at the 4-position and the electron-releasing
groups at 5-position. [3] The low regioselectivity of these reactions is the major disadvantage
of this method as a preparative procedure. The accepted mechanism for these reactions
is a concerted 1,3-dipolar cycloaddition. Kinetic data and the regio- and stereoselectivity
of these reactions strongly support this mechanism. However, the reactions involving
ionic azides (e.g., sodium azide) follow a nonconcerted ionic mechanism. These
mechanisms have been discussed and documented in reviews. [76,77]
N-Unsubstituted 1,2,3-triazoles are prepared by the direct addition of hydrazoic acid
or an azide ion to alkynes but it is often more convenient to obtain these compounds by
removal of a N-substituent from a 1H- or2H-triazole.
A. C. TomØ, Section 13.13, Science of Synthesis, 2004 Georg Thieme Verlag KG