Acetonitrile: acylation with

Acrylate 96 was acylated with acetyl chloride to deliver the acetate 97 in 98% yield (Scheme 4.16). C-Acylation of 97 was achieved at the (3-position of the acrylate in the presence of triethylamine in acetonitrile with acid chlorides 98a and 98b gave benzoylacry-lates 99a and 99b in 91% and 66% yield, respectively. 

The synthesis of rofecoxib can be achieved by several different routes (Drugs Fut., 1998). A highly efficient synthesis for rofecoxib was recently described (Therien et al., 2001). As illustrated in Scheme 79, acetophenon (i) is prepared according to the literature, by Friedel-Crafts acylation with thioanisole. Oxidation with MMPP (magnesium monoperoxyphthalate hexahydrate) affords the sulfone (ii), which is reacted with bromine in chloroform in the presence of a trace amount of AICI3, to give (iii). Bromoketone (iii) is than coupled and cyclized in a second step, one-pot procedure with phenylacetic acid. Firstly, the mixture of bromoacetophenone (iii) and phenylacetic acid in acetonitrile is treated with... 

The reactions of 0-naphthol and 4-methoxyphenol with acetyl, propionyl, butyryl, 0-chloropropionyl and chloracetyl chlorides in acetonitrile produce some striking kinetic results109. The behaviour of acetyl, propionyl and n-butyryl chlorides fit reasonably well into the pattern for acetyl chloride in nitromethane and acetyl bromide in acetonitrile. However, with chloracetyl chloride the mechanism is essentially a synchronous displacement of covalently bound chlorine by the phenol and this process is powerfully catalysed by added salt with bond breaking being kinetically dominant. When no added salt is present the rate of hydrolysis of chloracetyl chloride is ca. 8000 times slower than that of acetyl chloride. Although, normally, in second-order acylation reactions, substituents with the greatest electron demand have been found to have the fastest rates, the reverse is true in this system. Satchell proposes that a route such as... 

When O-alkylated or O-acylated D-glucals are heated in 9 1 acetonitrile-methanol with thallium nitrate trihydrate, ring contraction occurs to give compounds 117 in about 50% yield following, it may be assumed, addition of the metal ion at C-2 and methoxyl at C-l to lead to intermediates that ring contract to the 2,5-anhydro products.128... 

Recently, acyl benzotriazoles have been described as 0-,N, and S-acylating agents (37). These agents are prepared easily by reacting benzotriazole with acyl chlorides. At-protected a-aminoacyl- or peptidoyl-benzotriazoles are coupled in aqueous acetonitrile solution with free amino acids or dipeptides (38). Under some specific conditions, hydroxyl carboxamides can be prepared directly from the corresponding hydroxyl acids without protection of the alcohol (39). 

Direct tri-0-alkylation of calix[4]arenes has been reported to lead to the syn/syn isomer using bases such as BaO, BaO/Ba(OH)2 or CaH2 in DMF " . The tribenzoate of the p-unsubstituted calix[4]arene, one of the first examples of selectively derivatized calix[4]arenes, was obtained as the anti-syn isomer (benzoyl chloride/pyridine) , while the tribenzoate of 2a obtained in toluene with iV-methylimidazole as base (70% yield) was described as the syn-syn isomer, assuming a partial cone conformation with an inverted phenol ring . Both tris(3,5-dinitrobenzoates) of 2a were obtained by acylation with 3,5-dinitrobenzoyl chloride/l-methylimidazole. While 95% of the syn-syn isomer was formed in acetonitrile, 70% of the anti-syn isomer was obtained in chloroform . 

Use. For glpc separation of catecholamines. Horning et at.1 converted these substances first into the trimethylsilyl ethers by reaction with trimethylsilyl-imidazole in acetonitrile acylation of primary and secondary groups was then effected by addition of N-heptafluorobutyrylimidazole. The resulting trimethylsilyl ether-heptafluorobutyryl (TMSi-HFB) derivatives were found to have excellent glpc properties.1... 

Equilibration of the Z-E isomers also occurs in acetonitrile.25 With 2-acetoxyphenylmethylene oxazolones, isomerization to the E isomer was observed.63 Isomerizations to benzamidocoumarin derivatives under photochemical conditions have also been reported 64,65 While the 2-oxazolin-5-ones are thermally stable, the introduction of a 4-acyl or aroyl group, a potential site for further reaction, markedly decreases the stability. Thus, when 2,4-dialkyl-4-aroyl-2-oxazolin-5-ones are heated to 180°, decarboxylation occurs readily with the formation of trisubstituted oxazoles in yields of 71-95%66 [Eq. (13)). 

Three recent papers deal with the improvement of the synthesis of norcocaine. First, oxidation of cocaine (24) with permanganate in acetonitrile, acidified with acetic acid, gave 95% yield (about 50% conversion) of norcocaine (25a) with some iV-benzoylecgonine ester (25b) this, with dioxan and HCl, underwent N- O-acyl migration to form the same product, similarly to N-benzoylecgonine itself. ... 

Primary and secondary amines react readily, hydroxyls rather less so. The compound to be analysed (1-2 mg) is dissolved in MBTFA (500 /il) and left at room temperature for 30 minutes. Higher temperatures may be necessary for the less reactive classes of compounds this needs to be established in practice. Compounds that do not readily dissolve may be dissolved in a 1 4 mixture of MBTFA with acetonitrile, pyridine, dimethyl sulpho-xide, THF etc. Excess of MBTFA does not have to be removed it elutes early in GC analysis. A combined procedure can be done in which the compound to be analysed, such as a phenolic amine, is silylated with bis(trimethylsilyl)trifluoroacetamide (BSTFA, 50/il) at room temperature overnight (or for shorter periods at higher temperatures), followed by acylation with MBTFA (5—50 /il) at 80 °C for 5 minutes. Any TMS-amino groups get acylated in these conditions [124-126]. Acylation with MBTFA can also be done on-column, which is even quicker [127]. 

Two variants of this basic strategy were developed the first route is shown in Scheme 13. Starting with ethyl 3-furancarboxylate, acylation with monomethylglutarate was effected with trifluoroacetic anhydride (TFAA) and phosphoric acid in acetonitrile to provide keto-furan 37 in 64% yield. Reduction of the ketone to 38 was achieved by treatment with EtaSiH and BFa EtaO (82%... 

Allylalion of the alkoxymalonitrile 231 followed by hydrolysis affords acyl cyanide, which is converted into the amide 232. Hence the reagent 231 can be used as an acyl anion equivalent[144]. Methoxy(phenylthio)acetonitrile is allylated with allylic carbonates or vinyloxiranes. After allylation. they are converted into esters or lactones. The intramolecular version using 233 has been applied to the synthesis of the macrolide 234[37]. The /i,7-unsaturated nitrile 235 is prepared by the reaction of allylic carbonate with trimethylsilyl cyanide[145]. 

To set the stage for the crucial carbene insertion reaction, the acetic acid side chain in 32 must be homologated. To this end, treatment of 32 with 1,l -carbonyldiimidazole furnishes imidazo-lide 33, a competent acylating agent, which subsequently reacts with the conjugate base of Meldrum s acid (34) to give 35. Solvolysis of this substance with para-nitrobenzyl alcohol in acetonitrile at reflux provides /Mceto ester 36 after loss of one molecule of ace-... 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

Treatment of N-benzoyl-L-alanine with oxalyl chloride, followed by methanolic triethylamine, yields methyl 4-methyl-2-phenyloxazole-5-carboxylate 32 <95CC2335>. a-Keto imidoyl chlorides, obtained from acyl chlorides and ethyl isocyanoacetate, cyclise to 5-ethoxyoxazoles by the action of triethylamine (e.g.. Scheme 8) <96SC1149>. The azetidinone 33 is converted into the oxazole 34 when heated with sodium azide and titanium chloride in acetonitrile <95JHC1409>. Another unusual reaction is the cyclisation of compound 35 to the oxazole 36 on sequential treatment with trifluoroacetic anhydride and methanol <95JFC(75)221>. 

A biphasic solvent system composed of tert-butyl methyl ether, -butanol, acetonitrile, and water (2 2 1 5) acidified with triflnoroacetic acid has been applied to fractionate anthocyanins. The npper (organic) phase acts as the stationary phase and the lower (aqneons) as the mobile phase. HSCCC has been applied to obtain several anthocyanin fractions from wine, red cabbage, black cnrrants, chokeber-ries, " bilberries (Vaccinium myrtillus) acylated anthocyanins, and also isolate individnal anthocyanins from wine. ... 

Azolides can also be used in amide syntheses with very good results when incorporated into copolymers. For example, reactions with l-acyl-4-vinylimidazole/divinylbenzene (96 4) copolymer in solvents like 1,4-dioxane or acetonitrile provide amides in good yields within 1-4 h [1221... 

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