Benzimidazole 2-propyl

Chemical Name 5-Chloro-1-[1-[3-(2,3-dihydro-2-oxo-1 H-benzimidazol-1-yl)-propyll -4-pi-peridinyl] -1,3-dihydro-2H-benzimidazol-2-one... 

CN (15 C/i)-methoxyacetic acid 2-[2-[[3-(l H-benzimidazol-2-yl)propyl]methylamino]ethyl]-6-fluoro-l,2,3,4-... 

CN 4 -[(l,4 -Dimethyl-2 -propyl[2,6 -bi-l//-benzimidazol]-l -yl)methyl][l,l -biphenyl]-2-carboxylic acid... 

Oxatomide (l- 3- [4-(diphenylmethyl)-l-piperazinyl] propyl)-l,3-dihydro-2H-benzimidazol-2-one) is an antiallergy drug. Akamatsu has reported that oxatomide decreases neutrophil-generated superoxide anion and hydrogen peroxide formation in a dose-dependent manner. The authors hypothesize that the drug is inhibiting NADPH-dependent oxygen metabolism within the neutrophil (Akamatsu et al., 1993). 

Abstract This presentation is a brief review on the resnlts of our work on iodine interaction with thioamides, selenoamides and amides. The thioamides, benzothia-zole-2-thione (BZT) (1), 6-n-propyl-2-thiouracil (PTU) (2), 5-chloro-2-mercap-tobenzothiazole (CMBZT) (3), N-methyl-benzothiazole-2-thione (NMBZT) (4), benzimidazole-2-thione (BZIM) (5), thiazolidine-2-thione (TZD) (6), 2-mercapto-pyridine (PYSH) (7), 2-mercapto-nicotinic acid (MNA) (8), 2-mercapto-benzoic acid (MBA) (9) and 2-mercapto-pyrimidine (PMT) (10) react with producing three type of complexes of formulae [(HL)IJ(l2) (HL= thioamide and n= 0, 1), [(HL) [I3 ] and [(HL-L)]+[l3 ]. The interaction of seleno-amides, derived from, 6-n-propyl-2-thiouracil (RSelJ) (R= Me- (11), Et- (12), n-Pr- (13) and i-Pr- (14)) with I, have also been studied and produced the complexes [(RSeU)IJ of spoke structure. These complexes are stable in non-polar solvents, but they decompose in polar solvents, producing dimeric diselenide compounds or undertake deselenation. 

Photolytic. Irradiation of trifluralin in hexane by laboratory light produced a,a,a-trifluoro-2,6-dinitro-A-propyl-jo-toluidine and a,a,a-trifluoro-2,6-dinitro-p-toluidine. The sunlight irradiation of trifluralin in water yielded a,a,a-trifluoro-A, 7 -dipropyl-5-nitrotoluene-3,4-diamine, a,a,a-trifluoro-A/ ,A/ -dipropyltoluene-3,4,5-triamine, 2-ethyl-7-nitro-5-(trifluoromethyl)benzimidazole, 2,3-dihydroxy-2-ethyl-7-nitro-l-propyl-5-(trifluoromethyl)benzimidazoline, and 2-ethyl-7-nitro-5-(trifluoromethyl)benzimidazole. 2-Amino-6-nitro-a,a,a-trifluoro-p-toluidine and 2-ethyl-5-nitro-7-(trifluoromethyl)benzimidazole also were reported as major products under acidic and basic conditions, respectively (Crosby and Leitis, 1973). In a later study, Leitis and Crosby (1974) reported that trifluralin in aqueous solutions was very unstable to sunlight, especially in the presence of methanol. The photodecomposition of trifluralin involved oxidative TV-dealkylation, nitro reduction, and reductive cyclization. The principal photodecomposition products of trifluralin were 2-amino-6-nitro-a,a,a-trifluoro-jo-toluidine, 2-ethyl-7-nitro-5-(trifluoromethyl)benzimida-zole 3-oxide, 2,3-dihydroxy-2-ethyl-7-nitro-l-propyl-5-(trifluoromethyl)benzimidazole, and two azoxybenzenes. Under alkaline conditions, the principal photodecomposition product was 2-ethyl-7-nitro-5-(trifluoromethyl)-benzimidazole (Leitis and Crosby, 1974). 

When trifluralin was released in the atmosphere on a sunny day, it was rapidly converted to the photochemical 2,6-dinitro-7V-propyl-a,a,a-trifluoro-/ -toluidine. The estimated half-life is 20 min (Woodrow et ah, 1978). The vapor-phase photolysis of trifluralin was studied in the laboratory using a photoreactor, which simulated sunlight conditions (Soderquist et al., 1975). Vapor-phase photoproducts of trifluralin were identified as 2,6-dinitro-Wpropyl-a,a,a-trifluoro-p-toluidine, 2,6 dinitro-a,a,a-trifluoro-jo toluidine, 2-ethyT7-nitro-l-propyl-5-(trifluoromethyl)benzimidaz-ole, 2 ethyT7-nitro-5-(trifluoromethyl)benzimidazole, and four benzimidazole precursors, reported by Leitis and Crosby (1974). Similar photoproducts were also identified in air above both bare surface treated soil and soil incorporated fields (Soderquist et al., 1975). 

Dihydroxy-2-ethyl-7-nitro-l-propyl-5-(trifluoromethyl)benzimidazole, see Trifluralin... 

R = ch3 /-(l-Carboxy-ethyl)-5-chlor-benzimidazol-3-oxid 81% Schmp. 197-202° r = ch2—CH2—sch, l-(l-Carboxy-3-methylthio-propyl)-... 53% Schmp. 218-222 ... 

Benzimidazole werden mit einer Mischung aus konz. Salpetersaure/konz. Schwefelsaure iiberwiegend in 5-Stcllung nitriert2-4, bei besetzter 5-Stellung wird vorwiegend am C6-Atom angegriffen207,254 z. B. 5-Nitro-2-propyl-benzimidazol (40% Schmp. 157-158")207 ... 

BENZIMIDAZOLE, 1- (3- (DIMETHYLAMINO)PROPYL) -2- (2-MORPHOLINOETHYL) -5-NITRO-, HYDROCHLORIDE... 

A mixture of 2.3 parts of l-(3-chloropropyl)-l,3-dihydro-2H-benzimidazol-2-one, 2.5 parts of 5-chloro-l,3-dihydro-l-(4-piperidinyl)-2H-benzimidazol-2-one, 3.2 parts of sodium carbonate, 0.1 part of potassium iodide and 80 parts of 4-methyl-2-pentanone is stirred and refluxed for 24 hours. The reaction mixture is cooled to room temperature and water is added. The undissolved product is filtered off and purified by column chromatography over silica gel using a mixture of trichloromethane and 10% methanol as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from 4-methyl-2-pentanone. The product is filtered off and recrystallized from a mixture of N,N-dimethylformamide and water, yielding 1.3 parts (30%) of 5-chloro-l-[l-[3-(l,3-dihydro-2-oxo-2H-benzimidazol-l-yl)propyl]-4-piperidinyl]-l,3-dihydro-2H-benzimidazol-2-one MP 242.5°C. 

To the solution of 5.35 g (28 mmol) [3-(lH-benzimidazol-2-yl)propyl]methylamine in 12.5 mL toluene was added by syringe 12.5 mL (11.42 g, 114 mmol) isopropenyl acetate. The reaction mixture was heated to reflux temperature, and stirred at that temperature for 1.75 hours, with reaction completion monitored by thin-layer chromatography (silica gel, eluting with 70% ethyl acetate/30% methanol). The product, N-[3-(lH-benzimidazol-2-yl)propyl]-N-methylacetamide, was obtained in quantitative yield. 

N-[3-(lH-Benzimidazol-2-yl)propyl]-2-(6-fluoro-2-hydroxy-l-isopropyl-l,2,3,4-tetrahydronaphthalen-2-yl)-N-methylacetamidemay be synthesized by another method ... 

To the mixture 22.7 g (0.54 mol) dry lithium chloride and 100 mL THF at -15°C was added 160 mL 2 molar lithium diisopropylamide (0.32 mol) in heptane/THF/ethylbenzene was added. Then a solution of 36.6 g (0.16 mol) N-[3-(lH-benzimidazol-2-yl)-propyl]-N-methylacetamide in 140 mL toluene was added, the solution was stirred for 2 hours, and a further 155 mL toluene was added. (S)-6-Fluoro-l-isopropyl-3,4-dihydro-lH-naphthalen-2-one (29.9 g, 0.15 mol), in 15 mL toluene was added. After stirring at -10°C for 4 hours, the resulting solution was added to 200 mL ice water. The pH of the resulting mixture was adjusted to 7-8 by addition of a 71 g concentrated hydrochloric acid. The organic layer washed with water, then the solvents removed under reduced pressure to give 96 g of (lS,2S)-N-[3-(lH-benzimidazol-2-yl)propyl]-... 

N-[3-(lH-Benzimidazol-2-yl)propyl]-2-(6-fluoro-2-hydroxy-l-isopropyl-l,2,3,4-tetrahydronaphthalen-2-yl)-N-methylacetamide,20.22 g (45.7 mmol), dissolved in 200 mL toluene at 40°C, was added by cannula over 40 min at 0°C to a suspension of sodium bis(2-methoxyethoxy)aluminum hydride in toluene, 40 mL (41.44 g suspension, 26.94 g sodium bis(2-methoxyethoxy)aluminum hydride, 133 mmol). The mixture was stirred at 0°C for 15 min, then at 35-40°C for 3 hours. The mixture was cooled to 25°C then added carefully to 70 g sodium hydroxide in 140 g ice. The resulting suspension was warmed to 25°C over 30 min, and the phases were separated. The aqueous phase was extracted with toluene and the organic phase was washed twice with 10% aqueous sodium hydroxide, once with water, then once with saturated brine. The toluene phase was dried and concentrated in vacuo to afford 20.61 g of(lS,2S)-2-[2- [3-(lH-benzimidazol-2-yl)propyl]methylmethylamino ethyl]-6-fluoro-l-isopropyl-l,2,3,4-tetrahydronaphthalen-2-ol as a colorless foam. 

To the mixture of 41.0 g (lS,2S)-2-[2- [3-(lH-benzimidazol-2-yl)propyl]methylmethylamino ethyl]-6-fluoro-l-isopropyl-l,2,3,4-tetrahydronaphthalen-2-ol, 240 mL water, and 240 mL toluene were added 22.4 g potassium hydroxide, and the mixture heated to 45-50°C for one hour. The resulting two-phase mixture was separated. To the organic phase was added 39.4 g (4.0 eq.) potassium carbonate sesquihydrate then a solution of 21.0 g (17.7 mL, 3.25 eq.) methoxyacetyl chloride in 33 mL toluene was added over two hours at 25-30°C, and the resulting mixture stirred for an additional 30 min. Water, 200 mL, was added to quench the reaction. The organic phase, containing mibefradil as the free base was added an ethanol. 

A solution of 23.9 g (100 mMol) of methyl 3,4-diaminobenzoate dihydrochloride and 11.7 g (110 mMol) of butyric acid chloride in 100 ml of phosphorus oxychloride is refluxed for 2 h. Then about 80 ml of phosphorus oxychloride are distilled off and the residue is mixed with about 150 ml of water. The oily crude product precipitated is extracted three times with 50 ml of ethyl acetate and after evaporation purified by column chromatography (600 g of silica gel eluant methylene chloride/methanol (30 1)). Yield of methyl-2-n-propyl-benzimidazole-5-carboxylate 15.0 g of oil (69%). 

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