The Synthesis of 1,5-Disubstituted Tetrazoles

Abstract

In a previous communication the synthesis of various alkylated pentamethylenetetrazoles was described (1). The activity of pentamethylenetetrazole (Metrazol) as an analeptic and respiratory stimulant was enhanced by the substitution of alkyl groups in the pentamethylene ring (2). In continuing our studies of the effect of structure on the pharmacologic activity in the tetrazole series it became of interest to determine whether similar relationships existed in a series of simple 1,5-disubstituted tetrazoles (I). Although a number of such structures in which one of the substituents on the tetrazole ring is an aromatic group are known (3), only a single example, 1,5-dimethyltetrazole, in which both substituents are aliphatic in character has been described.

Synthesis, Characterization and Anti-Cancer Activity of Hydrazide Derivatives Incorporating a Quinoline Moiety

“…112–114 °C (lit. [73] m.p. 113–115 °C); 1 H-NMR (CDCl 3 ): δ 7.49 (2H, t, J = 4.4 Hz, H2 and H6), 7.37 (1H, bs NH), 7.34 (2H, t, J = 8.0 Hz, H3 and H5), 7.13 (1H, t, J = 7.4 Hz, H4), 2.20 (3H, s, CH 3 ).…”

Remodeling and Enhancing Schmidt Reaction Pathways in Hexafluoroisopropanol

“…The byproduct could not be confirmed as amide due to lack of complete spectroscopic analysis. Tetrazole 2l : R f = 0.56 (2% MeOH/DCM); mp 173–177 °C (lit . mp 179.5–180 °C); IR (neat) 2928, 1501, 1450, 1096 cm –1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 1 H NMR (400 MHz, CDCl 3 ) δ 1.27–1.48 (complex, 6H), 1.70–1.80 (complex, 4H), 1.85–2.08 (complex, 10H), 2.75 (tt, J = 11.6, 3.5 Hz, 1H), 4.11 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 13 C NMR (100 MHz, CDCl 3 ) δ 25.0, 25.57, 25.63, 26.1, 31.6, 33.4, 33.7, 57.5, 157.7; HRMS (ESI) m / z calcd for C 13 H 23 N 4 [M + H] + 235.1923, found 235.1904.…”

“…1,5-Dicyclohexyl-1H-tetrazole 2l. 39 Following the general procedure A, a solution of dicyclohexylketone 1l (77.7 mg, 0.400 mmol, 1.0 equiv) and TMSN 3 (115 mg, 1.00 mmol, 2.5 equiv) in HFIP (1.0 mL) was treated with triflic acid (31.9 μL, 0.360 mmol, 0.90 equiv). The reaction mixture was stirred at room temperature for 6 h. Concentration, followed by quenching with triethylamine (≈0.05 mL), and purification using a 12 g flash column on an automated MPLC system (0−5% MeOH/DCM over 55 min) afforded tetrazole 2l (eluted between 1.0 and 1.2% MeOH/DCM) as a colorless crystalline solid, followed by a mixture of 2l and an unidentified byproduct (eluted between 1.2 and 1.9% MeOH/DCM; ≈88:12 ratio of 2l/ byproduct by 1 H NMR) and an impure mixture of 2l and byproduct (eluted between 1.9 and 2.6% MeOH/DCM).…”

“…Tetrazole 2l: R f = 0.56 (2% MeOH/DCM); mp 173−177 °C (lit. 39 mp 179.5−180 °C); IR (neat) 2928, 1501, 1450, 1096 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 1 H NMR (400 MHz, CDCl 3 ) δ 1.27−1.48 (complex, 6H), 1.70−1.80 (complex, 4H), 1.85−2.08 (complex, 10H), 2.75 (tt, J = 11.6, 3.5 Hz, 1H), 4.11 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 13 C NMR (100 MHz, CDCl 3 ) δ 25. 0, 25.57, 25.63, 26.1, 31.6, 33.4, 33.7, 57.5, 157.7 1,5-Diethyl-1H-tetrazole 2m.…”

Dyes derived from 3‐formyl‐2(1H)‐quinolone – synthesis, spectroscopic characterisation, and their behaviour in the presence of sulfhydryl and non‐sulfhydryl amino acids

“…The resulting solid was washed with water, dried, and recrystallised from water. Acetanilide 2c: yield 75%; mp 125°C (127°C [32]). Acetanilide 2c: yield 75%; mp 125°C (127°C [32]).…”