5-Tetrazolecarboxamides and their salts: new orally active antiallergy agents

Abstract

2-(Diethylamino)-6-nitrobenzonitrile (72). To a mixture of 3.82 g (0.02 mol) of 2-(ethylamino)-6-nitrobenzonitrile (73) and 3.2 g (0.02 mol) of ethyl iodide in 100 mL of DMF was added 0.96 g (0.02 mol) of 50% NaH (in oil) in portions. The mildly exothermic reaction was stirred for 10 min, poured into ice-water, and extracted into methylene chloride. Evaporation gave an oil that was passed through a short column of silica gel (20 g) with methylene chloride. The bright orange oil was collected and triturated with hexane to give 3.1 g of pure product, mp 39-41 °C.2-Nitro-5-(dimethylamino)benzoic Acid (75). Sodium cyanoborohydride (57 g) was added to a mixture of 54.6 g (0.21 mol) of commercial (70%) 2-nitro-5-aminobenzoic acid and 240 mL of formalin in 1200 mL of acetonitrile. The reaction mixture was stirred overnight and evaporated to one-third volume. The product crystallized as the hemihydrate: mp 187-189 °C; yield 50 g (100%). Anal. (C9H10N2O4-0.5H2O) C, , N. 5-(Dimethylamino)anthranilic Acid (76). A mixture of 10.5 g (0.05 mol) of the nitrobenzoic acid 75,5 g of 10% Pd on charcoal, and 25 g (0.3 mol) of cyclohexene in 200 mL of ethanol was heated at reflux for 3 h. The hot reaction mixture was filtered through Celite, the Celite pad was extracted three times with hot ethanol, and the combined ethanol filtrates were evaporated to one-third volume. Water was added to cloudiness, whereupon the pure product crystallized: yield 8.0 g (93%); mp 234-238 °C (lit.28 234-236 °C).

One-Pot Synthesis of 5-Aryl Diketo-1H-tetrazol Using 1-Methyl-1-methoxyethyl as Protective Group

“…4-甲氧基苯(6)与氰基甲酸乙酯反应得到 [7] . 其中化合物 6 对热不稳定, 文献中报道了合成过程中曾发生爆炸事 故 [7] , 并且整个合成路线冗长, 还需要使用三氟乙酸、 对 甲氧基苄氯、乙二硫醇等毒性较大的试剂, 条件苛刻, 操作不便, 不利于大量制备.…”

“…4-甲氧基苯(6)与氰基甲酸乙酯反应得到 [7] . 其中化合物 6 对热不稳定, 文献中报道了合成过程中曾发生爆炸事 故 [7] , 并且整个合成路线冗长, 还需要使用三氟乙酸、 对 甲氧基苄氯、乙二硫醇等毒性较大的试剂, 条件苛刻, 操作不便, 不利于大量制备. [7] ; (c) LiHDMS, THF, 60%～88% [2] ; (d) TFA, ethane dithiol-H 2 O (V∶V＝1∶1), r.t., 20 h, 70%～86%.…”

Cu2(OTf)2‐Catalyzed and Microwave‐Controlled Preparation of Tetrazoles from Nitriles and Organic Azides under Mild, Safe Conditions

“…Most recent studies on the subject rely on a classical paper in which benzyl azide derivatives and alkyl cyanoformates (ROCO-CN) were heated without solvent at 130 8C in a sealed tube; [3] tetrazoles of type 2 can be achieved in roughly 60-70 % yields, at best. To reduce the hazards inherent to heating these polynitrogenated starting materials and products, Demko and Sharpless investigated a "click chemistry" approach [4,5] by using mainly acyl cyanides (RCO-CN) and organic azides, which allowed them to obtain compounds of type 3 (1,5-disubstituted) under solvent-free conditions, without catalysts, at 120 8C.…”

“…Besides the additives shown in Table 1, many others (that is, Cu powder, AgSbF 6 , AgBF 4 , AgF, AgOAc, AuCl 3 , Au-(OTf) 3 , Ru/C, RuCl 3 , [RuCp*(PPh 3 ) 2 ]Cl 2 (Cp* = C 5 Me 5 ), [7] [Pd 2 (dba) 3 ]·CHCl 3 (dba = dibenzylideneacetone), PdCl 2 , Pt/C, PtCl 2 , PtCl 4 , Sc(OTf) 3 , and LaCl 3 ) were tested, but are not included in Table 1, as they turned out to be inactive. Table 1 shows that cycloaddition was only catalyzed by some copper salts (entries 4, 7-11, 13, and 14).…”

Szteránvázas azidok előállítása és réz(I)-katalizált dipoláris cikloaddíciói

“…Az 1980-as évek elején Klaubert és munkatársai számoltak be arról, hogy 130 °C-on történő hevítéssel állítottak elő tetrazolokat 60% körüli hozammal, kiindulási anyagként benzil-azid származékokat és alkil-cianoformátokat alkalmazva [77].…”