Product Class 13: 1,2,3-Triazoles

13.13.1.1.3.1.1.2 Method 2:
Addition of the Azide Ion to Alkynes
The azide ion undergoes addition to alkynes to give triazoles 82 in low to moderate yields
(Scheme 37). Better yields are obtained with alkynes bearing electron-withdrawing
groups. Almost quantitative yields (>98%) of 5-substituted 1H-1,2,3-triazole-4-carbaldehydes
are obtained from the reaction of alk-2-ynals with sodium azide in dimethyl sulfoxide,
at room temperature. [84] Generally the reaction is carried out in dimethyl sulfoxide or
dimethylformamide; sodium azide [84–87] is frequently used as the azide ion source but lithium
azide [88] and aluminum azide [89] have also been used. The mechanism of the reaction
probably involves the nucleophilic addition of the azide ion to the triple bond followed by
1,5-dipolar cyclization of the resulting vinyl anion. Addition of sodium azide to 1-aryl-5phenylpent-4-yne-1,3-diones
in refluxing dimethylformamide gives the corresponding 4-
(3-aryl-1,3-dioxopropyl)-5-phenyl-1H-1,2,3-triazoles 82 (R 1 = Ph; R 2 = COCH 2Bz, COCH 2CO-
4-Tol, 4-MeOC 6H 4COCH 2CO) in good yields. [86]
Scheme 37 Addition of Sodium Azide to Alkynes [84–86]
R2 R1 + NaN3 FOR PERSONAL USE ONLY
440 Science of Synthesis 13.13 1,2,3-Triazoles
DMSO
R 2
R 1
−
+
N
−
N
N
R 1 R 2 Yield (%) mp (8C) Ref
H H 11 – [85]
H Ph 40 148 [85]
Ph Ph 16 140 [85]
H CO2Me 49 145 [85]
CO2Me CO2Me 54 132 [85]
Ph CHO >98 – [84]
Bu CHO >98 – [84]
Ph COCH2Bz 72 87 [86]
Ph COCH2CO-4-Tol 72 122 [86]
Ph 4-MeOC6H4COCH2CO 60 79 [86]
H 3O +
R 1
R 2
R 1
N
N
N
−
The reaction of propynenitrile with aluminum azide (THF, reflux, 24 h) gives a mixture of
the triazoles 83 (32%) and 84 (47%) (Scheme 38). [89] The formation of the tetrazole ring results
from the addition of an azide ion to the cyano group.
A. C. TomØ, Section 13.13, Science of Synthesis, 2004 Georg Thieme Verlag KG
R 2
82
N
H
N
N