4,4´ꢀBiꢀ1,2,3ꢀtriazoles
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 6, June, 2015
1471
Scheme 1
25 mL of water). Bromine (0.6 mL, 11.0 mmol) was added dropꢀ
wise to the solution with continuous stirring, which was accomꢀ
panied by the gas evolution. The stirring was continued for more
3 h at room temperature. A precipitate formed was filtered. The
yield of the product was 2.2 g (96%), m.p. 127—128 C (methaꢀ
nol). Found (%): C, 47.37; H, 3.99; N, 16.70. C10H10BrN3.
Calculated (%): C, 47.64; H, 4.00; N, 16.67. 1H NMR (CDCl3),
: 7.19—7.36 (m, 5 H, Ph); 5.50 (s, 2 H CH2); 2.15 (s, 3 H,
CH3). 13C NMR (CDCl3), : 133.98, 131.84, 129.12, 128.63,
127.31, 120.86, 53.05, 8.30.
4ꢀBromoꢀ1ꢀphenylꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazole (1b) was synꢀ
thesized similarly. The yield on two steps starting from ethyl
5ꢀmethylꢀ1ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate was 86%,
m.p. 67—69 C. Found (%): C, 45.45; H, 3.42; N, 17.57.
C10H10BrN3. Calculated (%): C, 45.40; H, 3.39; N, 17.65. 1H NMR
(CDCl3), : 7.55—7.60 (m, 3 H, Ph); 7.46—7.48 (m, 2 H, Ph);
2,35 (s, 3 H, CH3). 13C NMR (CDCl3), : 136.28, 132.32, 129.91,
129.68, 124.73, 121.12, 9.29.
R = Bn (1a, 2a), Ph (1b, 2b)
Reagents and conditions: i. NiCl2, PPh3, Zn, THF, 50 C, 7 h;
ii. bis(pinacolato)diboron (pinB)2, Pd(OAc)2, SPhos, KOH, 120 C,
12—14 h.
, Cy — cyclohexyl
5,5´ꢀDimethylꢀ1,1´ꢀdibenzylꢀ1H,1´Hꢀ4,4´ꢀbiꢀ1,2,3ꢀtriazole
(2a). A. Anhydrous NiCl2 (0.52 g, 4.0 mmol) and Ph3P (4.2 g,
16.0 mmol) were placed into a Schlenk flask equipped with
a magnetic stirrer. Tetrahydrofuran (20 mL) was added through
a septum under argon. Zinc dust (0.26 g, 4.0 mmol) was added to
the resulting mixture at 50 C. The solution acquired brown red
color. After stirring for more 1 h, 1ꢀbenzylꢀ4ꢀbromoꢀ5ꢀmethylꢀ
1Hꢀ1,2,3ꢀtriazole (1a) (1 g, 4.0 mmol) was added and the mixꢀ
ture was stirred for more 3 h and poured into aqueous ammonia
(80 mL). The mixture was extracted with chloroform (3×50 mL),
the chloroform extract was washed with water (3×50 mL), dried
with anhydrous Na2SO4, the solvent was evaporated on a rotary
evaporator. The residue was purified from Ph3P by flashꢀchroꢀ
matography on silica gel (eluent light petroleum ether). The
residual compound was finally eluted with light petroleum ether—
ethyl acetate (2 : 1) mixture. The yield of 2a was 0.6 g (44%);
m.p. 172—173 C. Found (%): C, 69.86; H, 5.80; N, 24.30.
C20H20N6. Calculated (%): C, 69.75; H, 5.85; N, 24.40. 1H NMR
(CDCl3), : 7.19—7.34 (m, 10 H, Ph); 5.55 (s, 4 H, CH2); 2.57
(s, 6 H, CH3). 13C NMR (CDCl3), : 138.14, 134.63, 131.07,
128.99, 128.31, 127.22, 51.84, 9.21. MS, m/z: 344 [M]+ (30),
91 [C7H7]+ (100).
B. 1ꢀBenzylꢀ4ꢀbromoꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazole (1a)
(251 mg, 1 mmol), bis(pinacolato)diboron (152 mg, 0.6 mmol),
melted potassium hydroxide (168 mg, 3 mmol), palladium aceꢀ
tate (2.24 mg, 1 mol.%), and ligand SPhos (8.21 mg, 2 mol.%)
were placed into a Schlenk flask equipped with a magnetic stirꢀ
rer. The resulting mixture was heated in an oil bath to 120 C and
allowed to stand at this temperature for 12 h. The melt obtained
was cooled to room temperature, the product was dissolved in
dichloromethane and purified by column chromatography on
silica gel (eluent light petroleum ether—ethyl acetate, 2 : 1). The
yield of 2a was 161 mg (94%).
In conclusion, a suggested new preparative method for
the homocoupling of 1,2,3ꢀtriazole monohalo derivatives
makes it possible to synthesize 4,4´ꢀbitriazoles in quantiꢀ
tative yields. This synthetic method is favorably distinꢀ
guished from the known analogs by the use of readily availꢀ
able starting compounds and a simplicity of the experiꢀ
mental procedure, which does not require an inert atmoꢀ
sphere or a solvent. We currently investigate a possibility
of the extension of this method on other bromotriazoles.
Experimental
1
H and 13C NMR spectra were recorded on a Bruker ACꢀ300
spectrometer (400.13 MHz). Mass spectra were recorded on a Finꢀ
nigan MATINCOSSO mass spectrometer (electron impact (70 eV),
direct injection). LC HRMS spectra were recorded on a LTQ
Orbitrek mass spectrometer (ESI, eluent MeCN—HCOOH,
99 : 1). Elemental analysis was carried out on a CarboꢀErba
CHNꢀanalyzer. Chromatography was performed using Merck
Kieselgel silica gel (40/60). 2ꢀDicyclohexylphosphinoꢀ2´,6´ꢀ
dimethoxybiphenyl (SPhos) was commercially available from
SigmaꢀAldrich. Nickel chloride was dried by reflux in SOCl2;
THF was dried using the sodium—benzophenone system.
The starting ethyl 1ꢀbenzylꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀ
carboxylate and ethyl 5ꢀmethylꢀ1ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀ
carboxylate were synthesized according to the improved by us
procedures.10,11
.
1ꢀBenzylꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylic acid.11
A mixture of ethyl 1ꢀbenzylꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarbꢀ
oxylate (10 g, 0.04 mol), potassium hydroxide (3.4 g, 0.06 mol)
and water (100 mL) was heated with stirring until all the comꢀ
pounds were dissolved. Then, the solution was cooled, hydroꢀ
chloric acid was added to weakly acidify the medium. A white
precipitate formed was filtered. The yield was 8.0 g (92%); m.p.
169—170 C (cf. data in Ref. 11: m.p. 168—169 C).
5,5´ꢀDimethylꢀ1,1´ꢀdiphenylꢀ1H,1´Hꢀ4,4´ꢀbiꢀ1,2,3ꢀtriazole
(2b). 4ꢀBromoꢀ5ꢀmethylꢀ1ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazole (1b) (237 mg,
1 mmol), bis(pinacolato)diboron (152 mg, 0.6 mmol), melted
potassium hydroxide (168 mg, 3 mmol), palladium acetate (2.24 mg,
1 mol.%), and ligand SPhos (8.21 mg, 2 mol.%) were placed into
a Schlenk flask equipped with a magnetic stirrer. The mixture
was heated in an oil bath to 120 C for 14 h. The melt obtained
was cooled to room temperature, the product was dissolved in
dichloromethane and purified by column chromatography on
silica gel (eluent light petroleum ether—ethyl acetate, 2 : 1). The
1ꢀBenzylꢀ4ꢀbromoꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazole (1a). 1ꢀBenzꢀ
ylꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylic acid (2 g, 9.2 mmol)
was dissolved in aqueous КOH (0.6 g, 11.0 mmol of КOH in