Imidization, base catalyzed

SCHEME 2.14 Uncatalyzed, base-catalyzed, and reductive generation of QMs tethered to a naphthalene imide core, through the TSs TS-NI, TS-NI, and TS-NI, respectively [bond lengths are in A data in parentheses are for full R(U)B3LYP/6-31 +G(d,p) optimization in aqueous solution] (reproduced from Ref. [47] with permission from American Chemical Society). (See the color version of this scheme in Color Plates section.)... 

Electron-deficient nitriles, such as for instance trichloroacetonitrile and trifluoroacetonitrile (A=B A = N B = CCC13, CCF3), are known to undergo direct and reversible, base-catalyzed addition of alcohols providing O-alkyl trichloroacetimidates (1,50). This imidate synthesis has the advantage that the free imidates can be isolated as stable adducts, which are less sensitive to hydrolysis than their corresponding salts. 

Fig. 8.20. Two-step activation ofN-[(acyloxy)methyl] prodrugs, a) Cleavage of the ester bond, which may be enzymatic and/or nonenzymatic, is followed by decomposition of the N-(hy-droxymethyl) intermediate, b) For (V-(hydroxymethyl) derivatives of amides and imides, the decomposition is base-catalyzed, c) For N-(hydroxymethyl) derivatives of amines, the decomposition can be uncatalyzed or undergo acid or base catalysis (modified from [214]).

Base-catalyzed cyclization of A -benzoyl-a-chloroacetamide is a classical method used to prepare 2-phenyl-4(5//)-oxazolone. Extension of this methodology to the A -aroylcinnamides 35 afforded a series of 5-arylidene analogues 37 albeit in unstated yield (Scheme 6.12). " Thus, acylation of the sodium salt of a benzamide with a cinnamoyl chloride gave the imides 35 that were converted to 36 via a bromination-dehydrobromination sequence. Cyclization to 37 was affected with sodium hydride in 1,2-dimethoxyethane (DME). The authors noted that catalytic reduction of 37 afforded the 5-(arylidene)oxazolidine from which 37 could be regenerated in the presence of air. 

The oxidation by molecular oxygen or the base-catalyzed oxidative decarboxylation of saturated 5(4//)-oxazolones 278 yields diacylamines and provides an efficient procedure to prepare imides 279 from Al-acylamino acids (Scheme 7.90). 

N-Unsubstituted 1//-azepines are rare since, like the parent system, they tautomerize readily to the 3H-isomers in whose preparation they are often considered as transient intermediates (see Section 5.16.4.1.2(h)). This rearrangement is particularly apparent with 2-amino- and 2-alkoxy derivatives since stabilization of the 37/-azepine is then possible by amidine and imidate type resonance. For the CH2-containing tautomers the order of stability appears to be 3H > AH > 2H, a fact attested to by the facile thermal and base-catalyzed rearrangements of AH- azepines to the 3H-tautomers (72CB982) and the rarity and inherent instability of 2H-azepines. The latter are well established as intermediates in the formation of 3H- azepines (74JOC3070) but have been characterized only as their benzologues. 

Since the second solvent pair fall within the poor hydrogen bonding group of solvents, increased basicity of the organic base in these solvents would be consistent with the observed behavior. Based on the model compound studies, indications are that the base-catalyzed imidization process may involve a two-step mechanism, Jee Scheme 23. The first step corresponds to the complete or partial proton abstraction from the amide group with the formation of an iminolate anion. Since this iminolate anion has two possible tautomers, the reaction can proceed in a split reaction path to either an isoimide- or imide-type intermediate. Although isoimide model reactions indicate an extremely fast isomerization to the imide under the conditions employed for base-catalysis, all indications to date are that it is not an intermediate in the base-catalyzed imidization of amic alkyl esters. 

Initial investigations of base-catalyzed imidization of polymeric systems, in particular PMDA/ODA based polyfamic alkyl esters), have been difficult due to the insolubility of the polyimide precursor at imidization levels exceeding 40%. Nevertheless, preliminary studies indicate that the base-catalyzed polymer imidization reaction appears to be significantly slower at ambient temperatures as compared to the phthalamide model compounds. It is yet unclear whether this is a direct result of the conformational aspects associated with the polymer chain or solubility considerations arising from the less soluble, partially imidized polymer chain. Since much of the initial work involved IR studies of supported... 

Base-catalyzed trimerizations are facile also for example, trifluoromethyl cyanide trimer-izes in the presence of ammonia, presumably through the formation of the amidine intermediate (139 Scheme 77) (67JOC231). Similarly, perfluoro-n-propyl cyanide forms the 1,3,5-triazine in the presence of sodium methoxide, probably via the imidate (140 Scheme 78) (52JA5633). 

The base-catalyzed rearrangement of the cyclic imide (35) affords a 50% yield of the 1,6-naphthyridine (36) and a 20% yield of the isomeric 1,7-naphthyridine (37).61 Treatment of 38, obtained by hydrolysis and decarboxylation of 36, with phosphorus oxychloride is reported to give 5-chloro-8-hydroxy-1,6-naphthyridine (39).88... 

The different properties of ILs, with regard to their polarity, hydrophobicity, and solvent miscibility behavior through combination with different anions, are the reason for the different biocatalyst activities. Good to excellent activity of CALB was observed with a decrease in polarity and hydrophobicity and a viscosity increase of the ILs. In [bmim][PF6] a conversion of (R)-l-phenylethanol into the ester of 48.9% and an ee of 95.6% were achieved after 5h and 100% of (R)-l-phenylethanol was converted into the enantiopure (R)-l-phenylethyl acetate after a 1-day reaction. Immobilized CALB exhibited excellent stability, activity, and selectivity towards the (R)-enantiomer of 1-phenylethanol in [bmim][PF6]. In some research bis(trifluoromethylsulfonyl)imide-based ILs have been regarded as very suitable media for biocatalysis [39, 46, 50]. On the contrary, in the present work, lower suitability of the same IL was demonstrated. Since immobilized CALB catalyzed both hydrolytic and transesterification reactions, its enantioselectivity for long reaction times was lower. 

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). 

The base-catalyzed addition of alcohols to nitriles to give imidates proceeds well, if there are electron-attracting groups in the a-position. In such cases the Pinner synthesis is less effective, because nitrile basicity is less. TTiis shows that both methods are complementary. Recently attention has been paid to the long-known addition of alcohols to trichloroacetonitrile, since it was found that imidates prepared from protected saccharides, amino alcohols etc. and trichloroacetonitrile are useful reagents for the synthesis of nucleosides, disaccharides and other natural products. The trichloroacetimidic acid esters (240 equation 131) of fluorinated, unsaturated aliphatic alcohols °° and benzyl alcohol have been prepared for synthetic purposes. 

Schaefer, F. C., Peters, G. A. Base-catalyzed reaction of nitriles with alcohols. A convenient route to imidates and amidine salts. J. Org. 

This original Pinner method shown in Equation (1) is still widely used. Solvents such as ether, dioxane, dichloromethane, chloroform, benzene, and nitrobenzene are often used as diluents and as an aid to crystallization of the imidate salt. Methanol and ethanol are the most widely used alcohols in the Pinner reaction, but other alcohols have also been employed and have given satisfactory results. However, the use of substituted nitriles in the Pinner synthesis has some limitations, and some nitriles cannot be converted into corresponding imidates but form amides instead. Fortunately, it has been found that those nitriles which give poor yields under the acidic conditions of the Pinner synthesis give good yields under base-catalyzed conditions (Equation (2)) reported first by Nef, etc.146,147 The base-catalyzed and acid-catalyzed processes therefore complement each other. 

Pyridinium-7V-(irnidoyI)imides 110, prepared from the base-catalyzed reaction of jV-aminopyridinium salts and JV-ethoxycarbonyl imidates, undergo initial intramolecular cycloaddition in refluxing xylene to afford unstable triazoline intermediates 111, which rearomatize to triazoles in a second step (77JOC443). 

The unique attributes of "catalyzed resins are that they eliminate the need for secondary (after molding) pre-plate activation or "seeding" operations common to conventional plating-on-plastics (POP) processes. For molded circuit board manufacture, catalytic resins are used in two-shot (two-component) molding processes which form highly complex 3D plastic structures which are capable of being selectively plated without the need for plating masks or resists. Polymers currently available in a "catalytic" composition include only amorphous sulfone and imide based systems. 

The 1-phenylpyrazole ring of the acyclo C-nucleoside 771 was formed as shown in Scheme 200 by the base-catalyzed cyclodehydration of the imidic acid hydroxyl and hydrazono proton of the pyrido[2,3-6]pyrazin-... 

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