Product Class 13: 1,2,3-Triazoles

Scheme 68 Addition of Monosaccharide Azides to Perfluoroalkyl-Substituted
Phenyl Vinyl Sulfones [199]
O
O
N3
199
O
O O
R 1 = CF3, (CF2)3CF3, (CF2)5CF3
FOR PERSONAL USE ONLY
462 Science of Synthesis 13.13 1,2,3-Triazoles
+
R 1
SO 2Ph
toluene, reflux
17−21 h
72−75%
200 201
O
O
N
N
N
Other sugar-derived 1,2,3-triazoles are prepared by a one-pot substitution–cyclization–oxidation
procedure starting from D-arabinose and L-fucose. The key step in this process is
an intramolecular 1,3-dipolar cycloaddition of an azide to the C=C bond of an Æ,â-unsaturated
carboxylic ester. The resulting 4,5-dihydro-1H-triazole is readily aromatized by air
oxidation. [201] Analogous sugar-derived 4,5-dihydro-1H-1,2,3-triazoles (related to D-glucose
and D-galactose) are stable but can be aromatized in good yields to the corresponding triazoles
by oxidation with bromine. [202]
Maleimides and quinones have also been used as dipolarophiles in reactions with
aryl azides, [203–206] silyl azides, [207] (azidoalkyl)indoles, [208] glycosyl azides, [209] (1-azidoalkyl)phosphonates
[210] and Æ-azidocarboxylic esters. [210]
6-Deoxy-1,2:3,4-di-O-isopropylidene-6-[4-(trifluoromethyl)-1H-1,2,3-triazol-1-yl]-Æ-Dgalactopyranose,
(201,R 1 =CF 3); Typical Procedure: [199]
A soln of azide 199 (0.85 g, 3.0 mmol) and sulfone 200 (R 1 =CF 3; 0.57 g, 2.40 mmol) in toluene
(15 mL) was refluxed under argon for 17 h (TLC control). Then the solvent was evaporated
under reduced pressure and the residue was purified by column chromatography
(toluene/EtOAc 20:1); yield: 0.64 g (72%); mp 128–1308C; [Æ] D –49.2 (CHCl 3).
13.13.1.1.3.1.2.3 Method 3:
Addition of Azides to Strained Alkenes
Azides react with alkenes to yield 4,5-dihydro-1H-1,2,3-triazoles. Whereas unactivated alkenes
are sluggish in their reaction with aryl azides, in contrast strained bicyclic alkenes
are particularly reactive. [76] For example, the reaction of 4-bromophenyl azide with hex-1ene
(in excess) affords the corresponding 4,5-dihydro-1H-1,2,3-triazole in 89% yield after
5.5 months at room temperature. At elevated temperatures (>808C), extensive decomposition
of the 4,5-dihydro-1H-1,2,3-triazole is observed. [211] No detectable addition product
is observed when the same azide and cyclohexene are left for three months at room temperature.
Conjugated dienes are, however, much more reactive than the corresponding
mono-unsaturated alkenes. For example, the adduct from the reaction of cyclohexa-1,3diene
and 4-bromophenyl azide begins to crystallize after three days at room temperature
and, after 18 days, a 77% yield of the corresponding 4,5-dihydro-1H-1,2,3-triazole is obtained.
[211] On the other hand, phenyl azide and substituted phenyl azides react with norbornene,
in refluxing petroleum ether (60–90 8C) for three to four hours, to give the corresponding
1-aryl-4,5-dihydro-1H-1,2,3-triazoles in 51–93% yield. [212,213] Norbornene and
other strained alkenes also react with azidotrimethylsilane to give the corresponding 1-
(trimethylsilyl)-4,5-dihydro-1H-1,2,3-triazole adducts in high yields. [214] The reaction of
norbornene and dicyclopentadiene with several heterarylmethyl azides has been studied.
[132]
A. C. TomØ, Section 13.13, Science of Synthesis, 2004 Georg Thieme Verlag KG
O
O O
R 1