Product Class 13: 1,2,3-Triazoles

13.13.1.1.2.1.2 Method 2:
From Diazoalkanes and Imines, Oximes, or Diarylazines
The 1,3-dipolar cycloaddition of diazoalkanes to C=N bonds is a general method for the
synthesis of 4,5-dihydro-1H-1,2,3-triazoles and 1H-1,2,3-triazoles (Scheme 22). [4] It is an especially
useful method for the regioselective preparation of 1H-1,2,3-triazoles with bulky
substituents in positions 1 and 5. Imines are the most versatile C=N system to be used in
this method, but oximes and diarylazines can also be used.
Scheme 22 Addition of Diazoalkanes to Imines [55,56]
R 1
R 2
50
NR 3
+ R 4 CHN 2
13.13.1.1.2.1.2.1 Variation 1:
From Diazoalkanes and Imines
R
N
N
N
4
R3 R2 R1 4,5-Dihydro-1H-1,2,3-triazoles 51 are the expected products from the cycloaddition reaction
of imines 50 with diazoalkanes but in some cases they spontaneously aromatize to
the corresponding triazoles. When the 4,5-dihydro-1H-1,2,3-triazoles are the isolated
products they can be converted into triazoles by a large number of alternative procedures
(see Section 13.13.1.3).
The addition of diazoalkanes (especially diazomethane) to imines, to give 4,5-dihydro-1H-1,2,3-triazoles
51, is very well studied. [4] In general it is favored by the presence of
electron-withdrawing substituents in the imine, especially on an N-aryl moiety. [55,56]
Though kinetic investigations of this reaction show that it follows essentially a concerted
process and is not generally dependent on solvent polarity, a sizable increase in rate is
noticed in the presence of protic solvents such as water or alcohols. [57] For example, while
reaction of diazomethane with N-benzylideneaniline (52,Ar 1 =Ar 2 = Ph) does not occur in
dry ether, it does occur in aqueous dioxane giving the 4,5-dihydro-1H-1,2,3-triazole 53
(Ar 1 =Ar 2 = Ph) in 53% after eight days (Scheme 23). [55] This solvent system can be successfully
used for the preparation of 5-hetaryl-substituted 4,5-dihydro-1H-1,2,3-triazoles of
type 53 (Ar 1 = 2- or 3-pyridyl, 2-quinolyl). [58,59] Triethylaluminum and other aluminum
complexes have been used as catalysts in the reaction of diazomethane with imines. [50]
Scheme 23 Addition of Diazomethane to Diarylimines [58]
Ar 1
52
N
Ar 2
+ CH2N 2
FOR PERSONAL USE ONLY
430 Science of Synthesis 13.13 1,2,3-Triazoles
dioxane, H2O (cat.)
rt, 2−8 d
51
Ar 1
53
N
N
N
Ar2 Diazomethane undergoes addition to hexafluoroacetone imines 54 to give 4,5-dihydro-
1H-1,2,3-triazoles 55 as the sole product or to give mixtures of 4,5-dihydro-1H-1,2,3-triazoles
55 and 56 (the latter produced as a result of the addition of diazomethane to the
C=C bond) (Scheme 24). [60]
A. C. TomØ, Section 13.13, Science of Synthesis, 2004 Georg Thieme Verlag KG