Imidazole elimination

Molecular ions of l-(2-hydroxy-2-phenylethyl) imidazoles eliminate benzaldehyde. The parent ions of Crans-1-styrylimidazoles cyclize in a manner similar to their photochemical cyclization. ... 

Etintidine (84), an imidazole-containing histamine H-2 receptor antagonist, is an antiiilcer agent conceptually related to cimetidine and ranitidine. It can be synthesized by various routes one of which terminates by an addition-elimination reaction of propargylamine with substituted N-cyano-S-methylisothiourea derivative 83 to give etintidine (84) [28]. 

The action of triethylamine or 4-methylmorpholine on the imidazole derivatives 1 results in the formation of 4,5-dihydro-l/f-l,2-benzodiazepines 2, which eliminate imidazole on heating with ethanolic sodium ethoxide to give H-, 2-benzodiazepines 3.121 Details for compound 3 (R1 = Ph, R2 = Me) only were reported it was stated that other derivatives were obtained similarly but details were not given. 

In vanadium-dependent haloperoxidases, the metal center is coordinated to the imidazole system of a histidine residue, which is similarly responsible for creating hypochlorite or hypobromite as electrophilic halogenating species [274]. Remarkably, a representative of this enzyme class is capable of performing stereoselective incorporation of halides, as has been reported for the conversion of nerolidol to various snyderols. The overall reaction commences through a bromonium intermediate, which cyclizes in an intramolecular process the resulting carbocation can ultimately be trapped upon elimination to three snyderols (Scheme 9.37) [275]. 

The mechanism of the reaction has not been eiuddated. Presumably iodine eliminates the imidazole ring from N-substituted imidazole derivatives such as clotrimazole, and this then couples with diazotized sulfanilic acid to yield an azo dye. 

In a related procedure, chlorodiphenylphosphine, imidazole, iodine, and zinc cause reductive elimination of diols.298 (3-Iodophosphinate esters can be shown to be intermediates in some cases. 

Fig. 1—2 shows a Hammett diagram for 14 different imidazolides of benzoic acids with a wide range of substituents upon which the reactivity is strongly dependent for example, the difference in rate constants between jV-(4-nitrobenzoyl)imidazole and iV-(4-dimethylaminobenzoyl)imidazole under the same reaction conditions amounts to a factor of about 3000. The Hammett reaction constant p = + 1.85 for the series shown in Fig. 1—2 indicates clearly that the hydrolysis is following a nucleophilic addition-elimination reaction path. 

A two-step mechanism must be assumed for this very valuable reaction of carboxylic acids with CDI.[9] Obviously the first step is a nucleophilic attack of the carboxylic acid or —depending on the acidity —the carboxylate ion on the carbonyl group of CDI, leading after elimination of imidazole to a mixed anhydride of imidazole-iV-carboxylic acid and the attacking carboxylic acid. This intermediate must have a very short life-time since it has not been detected down to — 50 °C. Rapid cleavage of CO2 from this mixed anhydride involves exclusively the carbonyl group linked to the imidazole unit If... 

As compared to the carbamate synthesis above, an abnormal reaction course was observed in the reaction of m-tolyloxythiocarbonylimidazole with benzylmethylamine here the phenolate is exchanged instead of the imidazole, obviously because the substituent with the lower pK is eliminated 2163... 

These compounds can be converted either to 1,2-oxazetidin-3 -ones1105M107H1091 under elimination of C02 or to 4-oxazolidinones[ 1071 by treatment with imidazole ... 

Aldoximes are readily dehydrated with N, N -carbonyldiimidazole (CDI). An intermediate azolide is formed in the process under elimination of one mole of imidazole, which fragments into a nitrile through elimination of CO2 and a second mole of imid-azole.[1],[2]... 

An AT-dimethylsulfamoyl-protected 4-iodoimidazole is joined with N-tert-butoxy-carbonyl-4-piperidone via a Grignard reaction to give, in good yield after dehydration and elimination of the two protecting groups with concentrated HC1, 4(5)-( 1,2,5,6-tetra-hydropyridin-4-yl)imidazole as dihydrochloride c 151... 

An unusual observation was noted when ethanolic solutions of 2-alkyl-4(5)-aminoimidazoles (25 R = alkyl) were allowed to react with diethyl ethoxymethylenemalonate (62 R = H) [92JCS(P1)2789]. In addition to anticipated products (70), which were obtained in low yield ( 10%), the diimidazole derivatives (33 R = alkyl) were formed in ca.30% yield. The mechanism of formation of the diimidazole products (33) has been interpreted in terms of a reaction between the aminoimidazole (25) and its nitroimidazole precursor (27) during the reduction process. In particular, a soft-soft interaction between the highest occupied molecular orbital (HOMO) of the aminoimidazole (25) and the lowest unoccupied molecular orbital (LUMO) of the nitroimidazole (27) is favorable and probably leads to an intermediate, which on tautomerism, elimination of water, and further reduction, gives the observed products (33). The reactions of amino-imidazoles with hard and soft electrophiles is further discussed in Section VI,C. 

Tolterodine undergoes hepatic metabolism involving CYP450 2D6 and 3A4 isoenzymes. Therefore, elimination can be impaired by CYP450 3A4 inhibitors including fluoxetine, sertraline, fluvoxamine, macrolide antibiotics, imidazoles, and grapefruit juice. 

The hexahydropyrrolo[l,2- ]imidazole chloro cycloadducts 57a-c, as a 1/1 mixture of stereoisomers, underwent an elimination on treatment with l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in dimethyl sulfoxide (DMSO) at 100°C. It was not possible to isolate the desired dihydropyrroles 58a-c and a second elimination occurred to form the T-substituted pyrroles 59a-c respectively (Scheme 4) <1998J(P1)2061>. 

An access to iV-substituted 4,6-dioxo-imidazo[3,4-c]thiazoles 185 was developed considering first the reaction of 2-chloroethylisocyanate with methyl thiazolidine 4-carboxylate 183 that generated the ureide 184. Cyclization of the imidazole ring occurred in acidic medium via an addition-elimination mechanism and delivered the imidazothiazole 185 (Equation 81) <2001MI1117>. 

Considerable interest has been reported in the radiolytic reactions of radiosensitiz-ing nitroimidazoles such ns Metronidazole, 2-methyl-5-nitro-l//-imidazole-1-ethanol (52). Again loss of the nitro function as nitrite appears to be one of the principal events. The formation of nitrite from /-irradiation of the Ni(II) complex of the imidazole 52 arises by hydroxy radical attack to form the radical anion. This either eliminates nitrite or undergoes a four-electron reduction to a hydroxylamino derivative68,69. 

Another notable example of the anomalous behavior of imidazole ligands is the kinetic tram effect observed for the rates of substitution of 02 for CO in the hemes Fe(TPP)02L ([29], M = Fe, X = 02, L = Py, Pip, or l-Melm) according to Eq.(4)and Table 8 30). One of the three nitrogen donors in question, l-Melm, stabilizes the dioxygen adduct in a manner not to be expected from its basicity. The substitution is clearly of the SN1 type, the elimination of the 02 molecule being the rate-determining step. 

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