Ethyl imidazole-2-carboxylate

The amidine (5) (2.00 g, 8,0mmol) is added at 0°C to trifluoroacetic acid (2 ml). The solution is left to stand at room temperature (24 h). Absolute ethanol (20 ml) is added, and the solution is heated under reflux (4h) before removal of the solvent under reduced pressure. Ethyl acetate is added to the 

The isomeric 1-suhstituted imidazole-5-carboxylates are made by cyclization of 3-amino-2-alkylaminopropanoic acids with triethyl orthoformate followed by active manganese dioxide oxidation of the imidazoline product (see Section 3.1.1), or from IV-substituted glycine esters, which are formylated, converted into the enolates and then condensed with potassium thiocyanate 

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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]. 

Imidazole-2-carboxylates can be made by amidine cyclization (see Section 2.2.1 and Table 2.2.2), by reaction of an aminocarbonyl compound with thioxamate (see Section 4.1 and Scheme 4.1.6), and from 1-cyano-or 1-carbethoxy-substituted 4-amino-2-azabutadienes (see Section 3.2 and Scheme 3.2.3). An improved amidine cyclization treats trichloroacetonitrile with ami noacetaldehyde dimethyl acetal to give the amidine (5), which cyclizes with trifluoroacetic acid at room temperature to give 2-trichloromethylimidazole (Scheme 8.3.2). This is not purified, but converted immediately into ethyl imidazole-2-carboxylate or imidazole-2-carboxylic acid in high yields [10],... 

Collisionally activated dissociation (CAD) spectra have been used to investigate the structures of ions formed by the decarbonylation of 1-acetylimidazole under electron impact (see also CHEC-I). The results are best explained by the formation of nonclassical methyleneazolium ions (Scheme 3). The loss of CO2 from ethyl imidazole-1-carboxylate does not produce these ions but leads instead to ionized 2 (or 4)-methyl-4(or 2)Ff-imidazole <84BSB1057>. Thermal rearrangements of 1-acetyl- to... 

General procedure. 4-Cyanoimidazoles 1444 [1098] A mixture of ethyl 4-imidazole-carboxylate (33 g) and ammonium hydroxide (250 mL) was heated to 100 °C in a sealed glass vessel for 1-7 days. The mixture was then cooled and the solid 4-imi-dazolecarboxamide 1443 was recovered by filtration in near quantitative yield and air dried. Dehydration was carried out by heating a solution of 4-imidazolecarbox-amide 1443 (5 g) in PhPOCli (25 mL) at 80 °C for 12 h. The cooled reaction mixture was then poured over ice (200 mL) and adjusted to pH 11 with 50% aqueous sodium hydroxide. The 4-cyanoimidazole 1444 was isolated by extraction with ethyl acetate and concentration of the extracts in vacuo. 

Imidazole-4-carboxylic acid, ethyl ester pK, 5, 384 [Pg.29]

Imidazole-2-carboxylic acid, 4-methylr ethyl ester synthesis, 5, 474 Imidazole-4-carboxylic acid coupling, 5, 403 iodination, 5, 400 reactions... 

Imidazole-4-carboxylic acid, 5-amino-cyclization, 5, 583 decarboxylation, 5, 434—435 ethyl ester diazotization, 5, 414 synthesis, 5, 477... 

Imidazole-4-carboxylic acid, 5-methylamino-ethyl ester thermolysis, 4, 438 Imidazolecarboxylic acids decarboxylation, 5, 434—435 reactions, 5, 92, 434—435 Imidazolediazonium fluoroborates reactions, 5, 439 Imidazolediazonium salts reactions... 

Dihydro-l//-imidazol-2-yl) derivatives were prepared from ethyl 2,3,6,7-tetrahydro-5//-pyrido[l,2,3-e/e]-l,4-benzoxazine-2-carboxylates and ethyl 5-oxo-2,3-dihydro-5//-pyrido[l,2,3-e/e]-l,4-benzoxazine-2-carboxy-lates with 2M Me3Al in toluene and H2NCH2CH2NH2 at reflux temperature for 3 h (99EUP894796). 

For quantitative work, it is necessary to estimate the concentration of 5-amino-l-(P-D-ribofuranosyl)imidazole in aqueous solution. It seems that the only available method is the Bratton-Marshall assay, which was originally developed for the estimation of arylamines in biological fluids. The principle of the method is the spectrometric estimation of a salmon-pink colored dyestuff obtained by diazotation in situ, followed by coupling with /V-( 1 -naphthyl)ethyl-enediamine.65 The only remaining problem then is to know the molar extinction of this dye because pure samples of AIRs are not available. A value of 16800 at 520 nM was obtained for the dyes prepared from a model compound, 5-amino-l-cyclohexylimidazole-4-carboxylic acid (54), which is crystalline. A comparable molar extinction can be expected for the dye prepared from imidazole 55, if the carboxyl group does not exert too much influence on the chromophore. Actually, its influence is perceptible even with the naked eye, the dyestuff prepared from 53 having a somewhat different, wine-red color, with max>520 nM. The molar extinction for 55 is 17400 at 500 nM. When the decarboxylation of 54 was conducted under mild acidic conditions (pH 4.8, 50°C, 1 hour), estimation of 5-aminoimidazole 55 by the Bratton-Marshall method led to the conclusion that the reaction was almost quantitative.66 Similar conditions for the final decarboxylation were adopted in the preparation of samples of AIRs labeled with stable isotopes.58... 

RN 22232-54-8 MF C7H,oN202S MW 186.24 EINECS 244-854-4 CN 2,3-dihydro-3-methyl-2-thioxo-17/-imidazole-l-carboxylic acid ethyl ester... 

CN (R)-1 -(1 -phenylethyl)-1 //-imidazole-5-carboxylic acid ethyl ester... 

Halogenation of 106 with triphenylphosphine, iodine, and imidazole provided the iodo derivative 109. On treatment with lithium aluminum hydride, 109 was converted into two endocyclic alkenes, 110 and di-O-isopro-pylidenecyclohexanetetrol, in the ratio of 2 1. Oxidation of 110 with dimethyl sulfoxide - oxalyl chloride afforded the enone 111.1,4-Addition of ethyl 2-lithio-l,3-dithiane-2-carboxylate provided compound 112. Reduction of 112 with lithium aluminum hydride, and shortening of the side-chain, gave compound 113, which was converted into 114 by deprotection. ... 

By adding one equivalent of alcohol to CDI at room temperature with or without base it is possible to isolate the imidazole-iV-carboxylate, which then reacts with a second mole of ROH to yield the carbonate. As in the case of alcoholysis of imidazolides, the reaction can be accelerated so effectively with catalytic amounts of NaOC2H5 or ImNa that it takes place in most cases exothermically, even at room temperature. However, tert-butyl alcohol, even when in excess, affords with CDI and base catalysis at room temperature only the imidazole-N-tert-butylcarboxylate, obviously for steric reasons. At higher temperature the carbonic ester is formed. Mixed carbonates such as ethyl benzyl carbonate or ethyl terf-butyl carbonate can be prepared with two different alcohols added sequentially.C9],[229]... 

On intuition, a minute amount of water was added to the solvent (ethyl acetate) in the first crystallization experiment containing a molar excess of imidazole corresponding to 1, Regularly shaped crystals were formed within one hour. Such a crystal, subjected to X-ray analysis, has the structure as shown in Fig. 41 U1). Apart from the formation of the expected salt-type associate (carboxylate-imidazolium ion pair, cf. Sect. 4.2.2), two water molecules are present in the asymmetric unit of the crystal structure. This fact called our attention again to the family of serine protease enzymes, where water molecules are reported as being located in the close vicinity of the active sites 115-120),... 

An attractive alternative is to study intramolecular reactions. These are generally faster than the corresponding intermolecular processes, and are frequently so much faster that it is possible to observe those types of reaction involved in enzyme catalysis. Thus groups like carboxyl and imidazole are involved at the active sites of many enzymes hydrolysing aliphatic esters and amides. Bimolecular reactions in water between acetic acid or imidazole and substrates such as ethyl acetate and simple amides are frequently too slow to... 

CuCN-2LiCl. This can then be selectively allylated vith allyl bromide to provide the dibromoimidazole 36, which can now be magnesiated by treatment with a further equivalent of iPrMgBr, providing the ester-substituted imidazole 37 in 55% yield after carboxylation with ethyl cyanoformate [25]. 

Ochiai, who reported in 1936 the first synthesis of the imidazo[2,l-h]thia-zole system (36CB1650), transformed ethyl 2-mercapto-5-methyl-imidaz-oIe-4-carboxylate with monochloroacetone into 2-(acylalkylthio)-imidazole 36. Refluxing 36 in phosphorus oxychloride yields ethyl 3,5-dimethylim-idazo[2,l-h]thiazole-6-carboxylate. No cyclization could be achieved by heating 36 in acetic anhydride because N-acylation (to 37) inhibited further reaction to the bicyclic system. 

The acylation of 5-hydroxymethylimidazo[2,l-h]thiazoles 96 (with, e.g., R = H, R = Ph) has been reported (80FES896). In line with expectations, ethyl esters of imidazol[2,l-6]thiazole carboxylic acids on basic hydrolysis... 

This approach is used for the syntheses of fused heterocycles which have a [l,3]-heteroatom juxtaposition in one of the rings <1996CHEC-II(7)49>. The unambiguous synthesis of tetrahydro-3//-benzothieno[2,3- / imidazole 87, as a target for the potential treatment of anxiety disorders, was accomplished starting from commercially available ethyl 2-amino-4,5,6,7-tetrahydro-benzothiophene-3-carboxylate 85 the key formation of the bicyclic heterocycle occurred through a final acid-mediated cyclization of 86 (Scheme 17) <1997SC473>. 

The dihydrothiazol-2-ylidene (4) was generated by photolysis of matrix-isolated thiazol-2-carboxylic acid.12 Calculations suggested that the barrier to isomerization to thiazole is about 42.3 kcal mol 1 and that the carbene resembles the related imidazol-2-ylidene in structure. An ab initio study of hydroxyoxiranone predicted that the decarboxylation of the zwitterion (5) to form hydroxycarbene (6) would be favourable in vacuo but not in water.13 A theoretical study showed that dihalosulfenes (X2C=S02) are best viewed as dihalocarbenc-SO complexes with a carbon-sulfur bond order of approximately zero.14 hi a study directed at the elusive thionformic acid (7), tandem mass spectrometric methods were applied to isomeric ethyl thioformates.15 The results suggest that the radical cations generated have the carbene structure [(HS)C(OH)]+ ... 

In an initial step, 2-chloroacetic acid ethyl ester is reacted with formamide to give 5-methylimidazole-4-carboxylic acid ethyl ester. Then sodium in ammonia is used to convert that to 4-hydroxymethyl-5-methylimidazole-hydrochloride. Cysteamine HCI (HSCH2CH2NH2-HCI) is then reacted to give 4-(2-aminomethyl)-thiomethyl-5-methyl-imidazole dihydrochloride. Then N-cyanamido-5,5-dimethyl-dithio-carbonate (from cyanamid, KOH, CS2 and ((CH3)2S04) is reacted to give a further intermediate which is finally reacted with methylamine to give cimetidine. 

The oxidation of the hydroxymethyl group probably takes place more readily than nitration of the ring [124-127], However, the entry of a nitro group into the imidazole ring without oxidation of the hydroxymethyl group has been reported [107, 110]. Imidazolecarboxylic acids are not nitrated, and their nitro derivatives are therefore obtained by different methods. Nevertheless, the 4- and 5-mononitro-substituted compounds were isolated with the 4,5-dinitro derivative as impurity during the nitration of ethyl l-methylimidazole-2-carboxylate with a mixture of 100% nitric and sulfuric acids at 95°C [128],... 

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