Synthesis, Properties, Chemical Reactivity of 1,2,3-Triazole

1,2,3-Triazole is an unsaturated, aromatic, five-membered, π-excessive nitrogen heterocycle with a 6π electron ring  system, comprised of three regular nitrogen and two carbon atoms with two double bonds. Out of three nitrogen  atoms, one is a pyrrole type and the other two are pyridine types. All the atoms in 1,2,3-triazoles are sp2  hybridized  and available 6π electrons are delocalized around the ring, responsible for its aromatic character.

The ionization energy of 1,2,3-triazole is 10.06 eV, which is greater than imidazole (8.78 eV) and pyrrazole (9.15eV).

1,2,3-Triazoles are mainly classified into three groups: (1) monocyclic 1,2,3-triazoles, (2) benzotriazoles, and (3)  1,2,3-triazolium salts. The monocyclic 1,2,3-triazoles are further classified into three subclasses depending on the position of the NH proton. The 1H- and 2H-1,2,3-triazoles are in equilibrium in solution as well as in the gas phase and  are aromatic in nature, while the 4H-1,2,3-triazole is nonaromatic. The 1,2,3-triazolium salts also exist in two isomeric  forms as depicted in the following diagram.

Synthesis

Dimroth and Fester initially prepared 1H-1,2,3-triazole by heating an alcoholic solution of hydrazoic acid with  an acetone solution of acetylene at 100°C for 70 h. The same compound was also obtained by the reaction of NaN3 with acetylene in acid solution.

Azide ions undergo cycloaddition with alkynes to build 1,2,3-triazoles in moderate to high yields. Alkynes with  an electron-withdrawing substituent give quantitative yields of triazoles. A reaction of 2-alkynals with sodium azide  in DMSO or DMF afforded 5-substituted 1H-1,2,3-triazol-4-carbaldehyde.

Cycloaddition of Azide to Activated Alkenes

Ethyl 3-(nitrophenyl)acrylate reacting with sodium azide in DMF or DMSO at 25°C for 2 h gave ethyl 4-(pnitrophenyl)-1H-1,2,3-triazol-5-carboxylate in 41% yields.

Addition of Azide to Allenes

Phenyl azides undergo cycloaddition to methyl but-2,3-dienoate to give a mixture of methyl 1-phenyl-5-methyl- 4-carboxylate and methyl 1-phenyl-4-methyl-5-carboxylate in a 9:1 ratio.

Physical Properties

The parent 1H-1,2,3-triazole is a colorless liquid, highly soluble in water, with a density of 1.192, an mp of 23–25°C,  and a bp of 203°C. In a solid state it exists as a 1:1 mixture of 1H- and 2H-tautomers. The dipole moment of a tautomeric mixture in benzene at 25°C is 1.85 D. A pKa  of 1.17 of protonated 1H-1,2,3-triazole indicates that it is a weak base,  while a conjugated base of 9.4 indicates that it is a weak acid. 

UV (ethanol) λnm (ε): 210 (3.60). 

1 H NMR (DMSO-d6 ), δ (ppm): C4 –H, 7.791; C5 –H, 7.791; N–H, 12.0. 

13C NMR (DMSO-d6 ), δ (ppm): C4 , 130.6; C5 , 130.6.

Chemical Reactivity

The 1,2,3-triazole ring is very stable and normally not cleaved either by hydrolysis or oxidation, but reductive  cleavages do occur. Due to the presence of two pyridine-type nitrogen atoms in the ring, ease of quaternization is  decreased and requires vigorous conditions.

Electrophilic Reactions

1,2,3-Triazoles like other heterocycles undergo electrophilic substitution at carbon or at nitrogen. They are readily  alkylated at nitrogen by alkyl halide, dimethyl sulfate, and diazomethane. Under forcing conditions, 1,2,3-triazoles  also quaternized to form triazolium salts.

Protonation

1,2,3-Triazole with water forms hydronium ions and triazolium anions.

Alkylation

Alkylation of 1H-1,2,3-triazoles by alkyl halide and dimethyl sulfate usually gave 1-alkyl-1H-1,2,3-triazole, while  alkylation with diazomethane gave 2-alkyl-2H-1,2,3-triazoles.

Arylation Reaction

1H-1,2,3-Triazole on reaction with 2,4,6-trinitrochloro/fluorobenzene in DMF/DMSO gave N-arylated  1H-1,2,3-triazole.

Halogenation

1H-1,2,3-Triazole is easily brominated with bromine in water at 45°C and afforded 4,5-dibromo-1H-1,2,3-triazole,  while bromination with NaOBr in acetic acid afforded 1,4,5-tribromo-1,2.3-triazole.

Nitration

2-Methyl-2H-1,2,3-triazole on nitration with a mixture of nitric acid and sulfuric acid at 25°C gave 5-nitro-2- methyl-2H-1,2,3-triazole, which on further nitration at 100°C afforded 4,5-dinitro-2-methyl-2H-1,2,3-triazole.

Metalation Reaction

1-Phenyl-1H-1,2,3-triazole is lithiated at low temperature with n-butyllithium to give 1-phenyl-5-lithio-1H-1,2,  3-triazole and act as a precursor for electrophilic substitution reactions.

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