Imidazole 2-ethyl-4-methyl-5-phenyl

Enantiomers of 4-(4-fluorophenyl)-7(E)- [3-methoxy-4-(4-methyl-1H-imi-dazol-l-yl)phenyl]methylene -3,4,6,7,8,9-hexahydro-, and cis- and trans-4H,9aH-4-aryl-7(E)- [3-methoxy-4-(4-methyl-lH-imidazol-l-yl)phenyl] methylenejperhydropyrido[2,l -c] [1,4]oxazin-6-ones, furthermore ethyl cis- and frans-4H,9aH-6-oxo-4-(3,4,5-trifluorophenyl)-7(E)- [3-methoxy-4-(4-methyl-lH-imidazol-l -yl)phenylJmethylene perhydropyrido[l,2-flJ... 

Fig. 5.7 Structures of 1,3-b is (2,4,6-trim ethyl phenyl) im id azo l-2-yl id en e (IMes) and T,3-bis(2,4,6-tri-methyl phenyl)-4,5-dihydro-1 H-imidazol-2-ylidene (Hj-IMes).

Dimethyl-3-(2-oxo-2-phenyl-ethyl--bromid lagert sich beim Kochen mit Triethylamin in Acetonitril in 2-(2-Imino-5-phenyl-2,3-dihydro-oxazol-3-yl)-4,6-dimethyl-pyrimidin um. Aus diesem werden durch Kochen in Alkoholen mit 4-Methyl-benzolsulfonsaure als Katalysator 2-Alkoxy-l-(4,6-dimethyl-2-pyrimidyl)-4-phenyl-imidazole oder durch Erhitzen mit primaren oder sekundaren Aminen ebenfalls in Gegenwart von 4-Methyl-benzolsulfonsaure 2-Alkylamino-l-(4,6-dimcthyl-2-pyrimidyl)-4-phe-nyl-imidazole erhalten374 ... 

Die Umlagerung von 2-Amino-5-methyl-3-(2-oxo-2-phenyl-ethyl)-1,3,4-oxadiazolium-broraid mit heiBer wiiBriger Kaliumcarbonat-Losung zu l-Acetylamino-2-hydroxy-4-phenyl-imidazol wurde bereits im Bd. X/2, S. 345 beschrieben. 

Wird die Ringerweiterung statt mit Bortrifluorid mit Meerwein-Reagens durchgefuhrt, so erhalt man mit Benzonitril aus 2-Methyl-3-phenyl-2H-azirin hauptsachlich l-Ethyl-2,5-diphe-nyl-4-methyl-imidazol und aus 3-Methyl-2-phenyl-2H-azirin 1-Ethyl-2,4-diphenyl-5-methyl-imidazol44°. 

Dabei entstchcn aus 1-substituierten Imidazolen wie z.B. l-Benzyl-2-methyl- oder 1,2-Dime-thyl-imidazol unter Verbrauch von zwei Aquivalenten Benzoesaure-chlorid die 1-substituierten 2-(2-Benzoyloxy-2-phenyl-ethenyl)-imidazole wie z.B. 2-(2-Benzoyloxy-2-phenyl-etheny1)-l-benzyl- (97%) oder 2-(2-Benzoyloxy-2-phenyl-ethenyl)-l-methyl-imidazol (93%), die zu 1-Ben-zyl-2-(2-oxo-2-phenyl-ethyl)- bzw. l-Methyl-2-(2-oxo-2-phenyl-ethyl)-imidazol hydrolysiert werden konnen 766 768. 

Die analoge Umsetzungmit l,2-Dimethyl-5-nitro-imidazol fiihrt zu l-Methyl-5-nitro-2-(2-oxo-2-phenyl-ethyl)-imidazol iV>17,. Mit Oxalsaure-chlorid-ethylester als Acylierungsreagens wird 2-(2-Ethoxycarbonyl-2-oxo-ethyl)-l-methyl-5-nitro-imidazol erhalten1073. 

Aus 2-Methyl-imidazol selbst entsteht unter Verbrauch von drei Aquivalenten Benzoesaure-chlorid l-Benzoyl-2-(2-benzoyloxy-2-phenyl-e(henyl)-imidazol (85%), dessen Hydrolyse 2-(2-Oxo-2-phenyl-ethyl)-imidazol (83%) liefert767 ... 

These compounds can initiate anionic polymerisation of epoxides, and when R, = H the secondary amine can react by addition to an epoxide group. Farkas and Strohm 64> have studied the reaction of 2-ethyl-4-methyl imidazole with phenyl glycidyl ether and BADGE resin using chemical analysis and proton NMR spectroscopy. They found that the imidazole readily forms adducts with epoxide of 1 1 and 1 2 molecular ratio ... 

Ac, acetyl AIBN, azobis(isobutanonitrile) All, allyl AR, aryl Bn, benzyl f-BOC, ferf-butoxycarbonyl Bu, Butyl Bz, benzoyl CAN, ceric ammonium nitrate Cbz, benzyloxycarbonyl m-CPBA, m-chloroperoxybenzoic acid DAST, diethylaminosulfur trifluoride DBU, l,8-diazabicyclo[5.4.0]undec-7-ene DCC, /V. /V - d i eye I oh e x y I c ar bo -diimide DCM, dichloromethyl DCMME, dichloromethyl methyl ether DDQ, 2,3-dichloro-5,6-dicyano-l,4-benzoquinone DEAD, diethyl azodicarboxylate l-(+)-DET, L-(+)-diethyl tartrate l-DIPT, L-diisopropyl tartrate d-DIPT, D-diisopropyl tartrate DMAP, 4-dimethylaminopyridine DME, 1,2-dimethoxyethane DMF, /V./V-dimethylformamide DMP, 2,2-dimethoxypropane Et, ethyl Im, imidazole KHMDS, potassium hexamethyldisilazane Me, methyl Me2SO, dimethyl sulfoxide MOM, methoxymethyl MOMC1, methoxymethyl chloride Ms, methylsulfonyl MS, molecular sieves NBS, N-bromosuccinimide NIS, /V-iodosuccinimide NMO, /V-methylmorpho-line N-oxide PCC, pyridinium chlorochromate Ph, phenyl PMB, / -methoxvbenzyl PPTs, pyridiniump-toluenesulfonate i-Pr, isopropyl Py, pyridine rt, room temperature TBAF, tetrabutylammonium fluoride TBS, ferf-butyl dimethylsilyl TBDMSC1, f-butylchlorodimethylsilane Tf, trifhioromethylsulfonyl Tf20, trifluoromethylsulfonic anhydride TFA, trifluoroacetic acid THF, tetrahydrofuran TMS, trimethylsilyl TPAP, tetra-n-propylammonium perruthenate / -TsOH. / -toluenesulfonic acid... 

N-(4-Dimethylamino-phenyl)- E16a, 96 [- N(OH) - N = NH-Spalt.] N-Methyl-N-[2-(2-pyridyl)-ethy]]-E16a, 128 (R-NH-OH + En) N-Methyl-N-[2-(4-pyridy )-ethyl]-E16a, 129 (R-NH-OH + En) Imidazol 4(5)-(l-Hydroxy-cyclo-pentyl)- E8c, 157 (Br-imidazol/... 

The quaternization of 1-substituted imidazoles is a facile reaction which leads to a stable quaternary salt via an 5n2 reaction (Scheme 16) which may be affected by steric factors. It has been shown (78AHC(22)7l) that the effects of fV-aryl substituents on rate constants for the quaternization of imidazoles can be correlated using a Hammett equation. The value of p (-0.45) for the ethylation of imidazoles shows little sensitivity to substituent effects, but this is to be expected since the basic pK values of the fV-aryl compounds do not vary widely, and the rate of alkylation must depend on the basicity of the nitrogen being quaternized. Certainly the expected sequence of reactivities, 1-methyl > 1-benzyl > 1-phenyl, is observed in the ethylation of 1-substituted imidazoles with iodoethane in ethanol or acetone, and although only qualitative observations are available, l-methyl-4-and -5-chloroimidazoles react less readily than 1-methylimidazole. Considerable experimental difficulty is experienced in quaternizing nitro-substituted imidazoles. 

A reaction which is applicable to the synthesis of imidazoles substituted at C-4 by sulfur substituents is the interaction of a-chloro-a-phenyl thioketones (prepared from the corresponding diazoketones) with ammonia and carboxylic acids. Although the detailed reaction course is yet uncertain, it bears a close resemblance to the reactions of a-chloro ketones with amides. The method has been used to prepare 2-ethyl-4-methyl-5-phenylthioimidazole (145) using ammonia, propanoic acid and 1-chloro-l-phenylthiopropanone (Scheme 82). 

Suitably substituted 1,2-diamines and derivatives can by cyclized into 2H-imidazoles either by photolytic or thermal treatment in the presence of base. The 2/f-imidazole products, however, cannot always be thermally isomerized to the 1/f-isomers. The migratory aptitudes of 2-substituents have been shown to lie in the order methyl[Pg.15]

Triphenyloxazole (5g), formamide (40g) and liquid ammonia (lOOtnl) are heated in an autoclave at 200-210°C (5h). The brownish reaction product is poured into water, and the flocculent precipitate is filtered, washed with water and recrystallized from ethanol (4.3 g, 85%), m.p. 273°C. Similarly prepared are 2,5-diethyl-4-phenyl- (25%), 2-methyl-4,5-dipropyI-(70%) [41], 4-eihyl-5-phenyl- (50%), 4-phenyl-5-propyl- (40%) and4-benzyl-5-ethyl imidazoles (5%) [40]. From 2-methyloxazole-4-carboxylic acid boiled at 150°C in a sealed tube with aqueous ammonia is obtained 2-methylimidazole (22%) boiling with aniline gives 2-methyl-l-phenylimidazole (67%) [52]. 

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