Imidazole imidic acid

In orthoesters (458 Scheme 84) one alkoxy group can be replaced by aminoacyl groups, by aminosul-fonyl groups or by the 1-imidazolyl group on reaction with ureas,imides, salicylamide, N-alkylsulfonamides in the presence of Lewis acids or with imidazoles under acid cat ysis. Excess aryl isocyanates convert orthoformates to acetals of parabanic acid. ... 

Scheme 2 Synthesis of the linear dyad 1. (a) Imidazole ropionic acid (10 1, v/v), 140°C, 4 h (26%) (b) Pd(PPh3)4], K2CO3/H2O, toluene, 80°C, 16 h (c) propionic acid, 150°C, 16 h (d) Pd(PPh3)4], K2CO3/H2O, toluene, 80°C, 16 h, 72% (e) 4-bromo-aniline, propionic acid, 150°C, 16 h, 88% (/) [PdCl2(dppf)] CH2CI2, bis(pinacolato)diboron, 1,4-dioxane, KOAc, 70°C, 16 h, 78% (g) [Pd(PPh3>4], K2CO3/H2O, toluene, 80°C, 16 h, 40% (h) ethanolamine, K2CO3, 160°C, 0.5 h, 20%. Route A one-pot imidization. Route B base-promoted coupling reaction between napthalene monoimide derivatives...

Later we reported [84] the (V-aiylation of imidazoles, imides, amines, amides, and sulfonamides with arylboronic acids using a recyclable Cu(0Ac)2 H20/[bmim] [BF4] system in the absence of a base or additive to afford the corresponding (V-arylated products in good to excellent yields. 

Similar Neber rearrangements were used to produce 528, an intermediate for an efficient synthesis of 2-imidazol-2-yl acetates 530 (equation 234). Condensation of the a-amino ketals 528 with imidates 529, followed by cyclization in refluxing acidic dioxane, yielded 2-imidazol-2-yl acetates 530 in a one-pot reaction. 

An interesting approach to maleimide-terminated phenoxy resin has recently has described (42). para-Maleimidobenzoic acid was reacted with diglyci-dylbisphenol-A epoxy resin in the presence of catalyst to provide the bismale-imide of Fig. 13. Instead of diglycidyl bisphenol-A, linear epoxy resin pre-polymers can be used in this reaction to form a maleimide terminated phenoxy resin. Another suitable functionalized monomaleimide is m- or p- N-(hydroxyphenyl) maleimide which is synthesized from maleic anhydride and m-aminophenol in DMF as a solvent at 70 °C. The purified hydroxyphenyl maleimide was reacted with epoxy resin to form novel BMIs as outlined in Fig. 14. The new BMI and phenoxy oligomers polymerize at temperatures of 200-220 °C, but the cure temperatures can be significantly lowered when catalysts such as imidazoles or triphenylphosphine are added. The cured homopolymers show Tg of 140 and 230 °C for the n = 2 and the n = 1 polymer, respectively(43). 

The condensation of 1,4-diamines with a variety of carboxylic acid derivatives, e.g. imidate esters, orthoformic esters, /V-ethoxycarbonylthioamides (77JOC2530), nitriles and ethoxyacetylene, produces the cyclic amidine linkage —N = C(R)NH— (67AHC(8)2l, p. 40). Cyclic ureas, —NHC(0)NH—, have been similarly produced using carbonyl chloride, A, A -carbonyldi imidazole, carbon monoxide, thiocarbonyl chloride or carbon disulfide (67AHC(8)21, p. 38). 

Hoskins and Crout6 have carried out the selective esterification of retronecine (12) at C-9 in moderate yield with simple acids using NN -dicyclohexylcarbodi-imide. With a/3-unsaturated acids and bulky a-trisubstituted acids, the use of /VJV -carbonyldi-imidazole, with prior formation of the acyl-imidazole, gave reasonable yields of the C-9 monoesters of (12). The regiospecificity of this... 

Surprisingly, it is only a very recent recognition that protic ionic liquids can serve as proton transfer electrolytes in hydrogen-oxygen fuel cells. A current report from the laboratory of Watanabe [40] describes the performance of a hydrogen electrode utilizing, as the electrolyte, the salt formed by proton transfer from the acid form of f>/i-trifluoromethanesulfonyl imide (HTFSI) to the base imidazole. 

This report covers two topics (1) The generation of 2-thioxo-2,4-dihydro-3fT-imidazol-l-ium-l-imides as intermediates in the course of [3+2] cycloaddition reactions of azoalkenes and thiocyanic acid resulting in the formation of l-aminoimidazole-2-thione derivatives some further reactions of these heterocycles are presented as well. (2) The rhodium-catalyzed intramolecular interaction of co-diazenyl a -diazo ketones giving rise to the formation of mostly two cyclic azomethine imine isomers with an exocyclic terminal nitrogen atom and with all three... 

Dihydroxyimidazo[4,5-c]pyridine (3-deazaxanthine 436 R = H) and related 2-substituted derivatives (436 R = Cl) and (438) were prepared from the requisite imidazole 4-acetamide-5-carboxylic acid esters (435) and (437) by base-catalyzed cyclization to the imide structure (63JOC304l). 

Microwave irradiation of a mixture of an acid anhydride, an amine adsorbed on silica gel, and TaCl5/Si02 is a solvent-free method for the synthesis of A-alkyl and A-aryl-imides [47]. Ni(II) promotes the conversion of an acrylamide to ethyl acrylate via a Diels-Alder adduct with (2-pyridyl)anthracene [48], Aromatic carboxylic acids [49] and mandelic acid [50] are efficiently esterified with Fc2(S04)3 XH2O as catalyst. Co(II) perchlorate in MeOH catalyzes the methanolysis of acetyl imidazole and acetyl pyrazole [51]. Hiyama et al. used FeCb as a catalyst for the acylation of a silylated cyanohydrin. The resulting ester was then cyclized to 4-amino-2(5H)-furanones (Sch. 5) [52]. 

The general approach of amidine cyclization ha.s been applied to the synthesis of a variety of 2-substitutcd imidazoles. Aminoacetaldehyde dimethyl and diethyl acetals are readily available commercially, and the N-subsiituted derivatives can be made with little difficulty, providing access to 1-substituted imidazoles on reaction with a suitable imidate. Thus, methyl -hydroxypropanimidate (2), prepared from 3-hydroxypropanenitrilc, and methanolic HCl, condenses with an aminoacetaldehyde acetal to give the amidine hydrochloride (3), which ring closes when heated in acidic medium to form the 1-substituted 2-hydroxyethylimidazolc (4) (Scheme 2.2.3) [6J. The reaction has been adapted to the preparation of 2-arylimidazoles [5, 7-11],... 

The aldehyde (5) can be made in high yield from the amidine (6) via the unisolated 2-dichloromethylimidazole (Scheme 2.2.3). Dichloroacetonitrile is converted into its imidate with methanolic sodium methoxide, and then into the amidine with aminoacetaldehyde dimcthylacetal. When (6) is heated in formic acid it is converted almost quantitatively into the 2-carbaldehyde the use of trifluoroacctic acid at reflux gives around 60% of (5). Using essentially the same method, imidazole-2-carboxylic acid and its ethyl ester can also be made veiy efficiently when trichloroacctonitrilc and the acetal arc used to prepare the amidine [16],... 

The earliest method of this type was the old Marckwald synthesis (1] in which a suitable a-aminocarbonyl compound is cyclized with cyanate, thiocyanate or isothiocyanatc. More recent modifications have employed the acetals of the a-amino aldehyde or ketone or an a-amino acid ester. The two-carbon fragment can also be provided by cyanamide, a thioxamate, a carbodiimidc or an imidic ester. When cyanates, thiocyanates or isothiocyanates are used, the imidazolin-2-ones or -2-thiones (1) are formed initially, but they can be converted into 2-unsubstituted imidazoles quite readily by oxidative or dehydrogenative means (Scheme 4.1.1). The chief limitations of the method arc the difficulty of making some a-aminocarbonyls and the very limited range of 2 substituents which are possible in the eventual imidazole products. The method is nonetheless valuable and widely used, and typically condenses the hydrochloride of an a-amino aldehyde or ketone (or the acetals or ketals), or an a-amino-)6-ketoester with the salt of a cyanic or thiocyanic acid. Usually the aminocarbonyl hydrochloride is warmed in aqueous solution with one equivalent of sodium or potassium cyanate or thiocyanate. An alkyl or aryl isocyanate or isothiocyanate will give an A-substituted imidazole product (2), as will a substituted aminocarbonyl compound (Scheme 4.1.1) [2-4]. 

TOSMIC can be converted into an A-tosylmethylimidic ester or thioester (10) which will react with an aldimine to form a 1,2,5-trisubstituted imidazole (Scheme 4.2.3). These esters (10) can be made from A-tosylmethylacetamidc (from the Mannich condensation of p-toluenesulfonic acid, formaldehyde and acetamide [10]), which is smoothly converted by P4S10 in DME into the thioamide which forms the 5-methylated imidate when treated with methyl fluorosulfonate in dichloromethane. Yields of the Al-tosylmethylimidic thioesters are good (65-93%) they are fairly stable crystalline solids which are best stored under nitrogen at —20°C. In reaction with an aldimine in the presence of sodium hydride or potassium t-butoxide (in DME -DMSO or... 

The reactions of amidines or guanidines with a-functionalized carbonyl compounds continue to be utilized for the synthesis of imidazoles. Thus, the mixed anhydride of acetic and chloroacetic acids reacts with symmetrical diarylguanidines to give l-aryl-2-arylaminoimidazolin-4-ones, and there is competitive formation of imidazoles and pyrimidines in the reaction of benzamidine with 3-bromobenzo-4-pyrones (18). Imidazoles are minor products, but are favored in nonpolar solvents. The use of a-dicarbonyl compounds with guanidine gives 2-amino-4-hydroxy-4-methyl-4//-imid-azoles, which give excellent yields of 2-aminoimidazoles on catalytic hydrogenation. " ... 

Moreover, aryl-oxazoles, -imidazoles [17], or-thiazoles [18], anhydrides [19], and imides [20] are accessible via intramolecular Heck-type carbonylations. In addition to typical acid derivatives, aldehydes [21], ketones [22], aroyl cyanides, aroyl acetylenes, and their derivatives [23] could be synthesized via nucleophilic attack of the acyl metal complex with the corresponding hydrogen or carbon nucleophiles. Even anionic metal complexes like [Co(CO)4] can act as nucleophiles and lead to aroylcobalt complexes as products [24]. 

Several examples have shown that the degree of activity resulting from synthesis is reproducible, as is the amino acid composition. In other cases, e.g., with p-nitrophenyl acetate, activity was quite variable. Nearly total inactivation by heat in aqueous solution has been demonstrated for some pyropolyamino acids other such systems are heat-stable in aqueous solution. In the p-nitrophenyl acetate system, the nature of the heat inactivation, if not the mechanistic reason for enhanced activity, is understood to involve both imide and imidazole residues. Differing interactions of these residues to produce loci of varying degrees of efficiency could help to explain the quantitative nonreproducibility of activity in separate syntheses. With OAA, selectivity of action was strict, in that several a-keto acids were not measurably acted upon under controlled conditions. The identification of the active locus for hydrolysis of the substrate p-nitrophenyl acetate supports the general inference of specificities, inasmuch as similarly prepared polymers have been shown not to be operative for other reactions, e.g., decarboxylation of OAA (17). 

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