Product Class 13: 1,2,3-Triazoles

Scheme 62 Addition of Sodium Phenylacetylide to Tosyl Azide [184]
Ph Na + −
FOR PERSONAL USE ONLY
458 Science of Synthesis 13.13 1,2,3-Triazoles
1. TsN 3 (1 equiv)
2. H 3O +
9%
1. TsN3 (excess)
2. H3O +
16%
Ph
170
N
N
N
Ts
N3
N
N
Ph
N
Ts
4-Azido-5-phenyl-1-tosyl-1H-1,2,3-triazole (171); Typical Procedure: [184]
A slurry of sodium phenylacetylide [prepared from PhC”CH (0.05 mol) and Na (0.05 mol)]
in dry Et 2O (25 mL) was added slowly to a stirred soln of tosyl azide (19.7 g, 0.10 mol) in dry
Et 2O (50 mL) at a rate which maintained the solvent at reflux. As the mixture was stirred
for 24 h a brown solid separated (15.2 g, 58%), which corresponds to a sodium salt of an
intermediate compound. Part of this compound (5.0 g) was treated with hot glacial AcOH
(10 mL) and a light yellow solid was obtained upon cooling. Two recrystallizations (glacial
AcOH) afforded pure triazole 171; yield: 0.52 g (16%); mp 170–1718C (dec).
13.13.1.1.3.1.2 Addition of Azides to C=C Bonds
The thermal cycloaddition of azides to alkenes is an important route to 1H-1,2,3-triazoles.
Azides undergo addition to a wide range of angle strained, unstrained, and unactivated
double bonds; to electron-rich double bonds such as enamines, enamides, enol ethers,
and ketene acetals; and to alkenes bearing one or two electron-withdrawing groups. [7] In
these reactions, 4,5-dihydro-1H-1,2,3-triazoles (D 2 -1,2,3-triazolines) are the addition products
but they can be aromatized to the corresponding triazoles by elimination of suitable
groups or by oxidation. In some cases the dihydrotriazoles aromatize spontaneously. Unlike
the case of alkynes, the reaction of azides with alkenes is highly regioselective. Because
of this, it may be convenient to prepare a triazole via the dihydrotriazole since at
the end the separation of regioisomers is not needed.
The synthesis of 1,2,3-triazoles via 1,3-dipolar cycloaddition of azides to alkenes requires
patience. It may take weeks to months to obtain reasonable yields of the desired
compound, especially if the C=C bond is not activated by electron-withdrawing or electron-donating
substituents. Increasing the reaction temperature is not always a solution
since it is restricted by the thermal lability of most dihydrotriazoles (they readily extrude
N 2).
13.13.1.1.3.1.2.1 Method 1:
Addition of Sodium Azide to Activated Alkenes
Sodium azide undergoes addition to alkenes with strongly electron-withdrawing substituents
to give N-unsubstituted 1,2,3-triazoles in good yields (Scheme 63). The mechanism
seems to involve the conjugate addition of the azide ion to the double bond, cyclization
of the resulting anion, and aromatization. The synthesis of triazoles 173 by the reaction
of sodium azide with Æ-nitroacrylic ester 172 (Y = CO 2Et) and Æ-nitro ketone 172 (Y = Bz)
are examples of this method. [185] Other nitroalkenes are converted into 1,2,3-triazoles in
the same way. [186] Similarly, triazole 175 is obtained, along with two minor dihydrotriazoles,
from the reaction of diethyl (4-nitrobenzylidene)malonate (174) with sodium
A. C. TomØ, Section 13.13, Science of Synthesis, 2004 Georg Thieme Verlag KG
171