Acid anhydride, mixed, with sodium

A method which avoids the use of hydrazides has been described by Weinstock " who demonstrated that mixed anhydrides interact with sodium azide in excellent yield. Thus the mixed anhydride (53) obtained from 2-phenylcyclopropane carboxylic acid and ethyl chloroformate is converted to the azide (54) after treatment for 30 minutes at 0° with sodium azide in aqueous acetone. It has been... 

Another method to obtain alcohols is to reduce the mixed carbonic acid anhydride prepared with Ethyl Chloroformate with an excess of Sodium Borohydride. This method uses less costly reagents thus it is more useful for synthetic transformations. 

Place in a dry test-tube 0 -5 g. of the compound and an equal bulk of pure phthahc anhydride, mix well together, and add 1 drop of concentrated sulphuric acid. Stand the tube for 3-4 minutes in a smah beaker of concentrated sulphuric acid or oil previously heated to 160°, Remove from the bath, allow to cool, add 4 ml. of 5 per cent, sodium hydroxide solution and stir until the fused mass has dissolved. Dilute with an equal... 

Mixed cellulose esters containing the dicarboxylate moiety, eg, cellulose acetate phthalate, have commercially useful properties such as alkaline solubihty and excellent film-forming characteristics. These esters can be prepared by the reaction of hydrolyzed cellulose acetate with a dicarboxyhc anhydride in a pyridine or, preferably, an acetic acid solvent with sodium acetate catalyst. Cellulose acetate phthalate [9004-38-0] for pharmaceutical and photographic uses is produced commercially via the acetic acid—sodium acetate method. 

Schimmel Co. attempted to acetylise the alcohol by means of acetic anhydride, but the reaction product only showed 5 per cent, of ester, which was not submitted to further examination. The bulk of the alcohol had been converted into a hydrocarbon, with loss of water. Ninety per cent, formic acid is most suitable for splitting off water. Gne hundred grams of the sesquiterpene alcohol were heated to boiling-point with three times the quantity of formic acid, well shaken, and, after cooling, mixed with water. The layer of oil removed from the liquid was freed fi-om resinous impurities by steam-distillation, and then fractionated at atmo.spheric pressure. It was then found to consist of a mixture of dextro-rotatory and laevo-rotatory hydrocarbons. By repeated fractional distillation, partly in vacuo, partly at ordinary pressure, it was possible to separate two isomeric sesquiterpenes, which, after treatment with aqueous alkali, and distillation over metallic sodium, showed the following physical constants —... 

Unsymmetrical as well as symmetrical anhydrides are often prepared by the treatment of an acyl halide with a carboxylic acid salt. The compound C0CI2 has been used as a catalyst. If a metallic salt is used, Na , K , or Ag are the most common cations, but more often pyridine or another tertiary amine is added to the free acid and the salt thus formed is treated with the acyl halide. Mixed formic anhydrides are prepared from sodium formate and an aryl halide, by use of a solid-phase copolymer of pyridine-l-oxide. Symmetrical anhydrides can be prepared by reaction of the acyl halide with aqueous NaOH or NaHCOa under phase-transfer conditions, or with sodium bicarbonate with ultrasound. 

The usual procedure of preparing acid azides, which involves treating an acid chloride with sodium azide,8,9 suffers from the disadvantage that it is often difficult to obtain pure acid chlorides in good yields from acids which either decompose or undergo isomerization in the presence of mineral acids.7 Synthesis of the azide by way of the ester and hydrazide10 has been used to circumvent this difficulty but is much less convenient. The present procedure permits ready formation of acid azides in excellent yields from mixed carboxylic-carbonic anhydrides and sodium azide under very mild conditions. 

An ester derived from prednisolone has found use as a topical ophthalmic antiinflammatory dmg. Cleavage of the side chain in prednisolone (31-1) with sodium periodate affords the corresponding carboxylic acid (30-2). Treatment of that product with propionyl chloride affords initially the ester at 17 along with some of the mixed anhydride. The anhydride is then hydrolyzed with a mild base to afford the 17-ester (31-3). Alkylation of the carboxylic acid with chloromethylchlorosufonyl chloride (from bromochloromethane and sulfonyl chloride) leads to the chloromethyl ester (31-4) and thus loteprednol [26]. 

An eco-friendly synthesis of 3, as shown in Scheme 14.10, commences with the solvent-free condensation of (S)-aminobutanol (32) and y-butyrolactone (35), affording the condensed alcohol 36 in quantitahve yield with water as the only by-product [31]. Potassium permanganate (KMnO4) mediated or ruthenium chloride (RUCI2) catalyzed (in combination with sodium hypochlorite) oxidahon of the resulting alcohol 36 afforded intermediate 37. Ammonia gas treatment of the mixed anhydride of acid 37 yielded the API 3 in comparable yields to those obtained in the first-generahon synthesis. 

Goodman and Chorev 75 found that the required a-aminoacyl azides 14 are best prepared by reaction of the mixed anhydride of the amino acid with sodium azide. This method led to slightly better yields than the nitrosylation of TV-formylaminoacyl hydrazide. Curtius rearrangement of the a-aminoacyl azide 14 yielded the isocyanate 16, which was subsequently trapped as 17 or 18 as shown in Scheme 2. Comparable yields were obtained by nitrosylation with tert-butyl nitrite. 76 Other methods of acyl azide formation have rarely been employed for PMRI-peptide synthesis. Only Fincham et al. 11 reported the use of trimethylsilyl azide to synthesize an acyl azide en route to a PMRI-peptide. 

A. Ch., [3], 37, 311.)—This is a standard method of preparing acid anhydrides. By using the sodium salt of one acid with the acid chloride of another, mixed anhydrides may be obtained. 

Attempts to synthesize C-terminal peptide aldehydes using other reductive techniques are less successful. 24"29 The reduction of a-amino acid esters with sodium amalgam and lithium aluminum hydride reduction of tosylated a-aminoacyldimethylpyrazoles resulted in poor yields. 26,29 The Rosemond reduction of TV-phthaloyl amino acid chlorides is inconvenient because the aldehyde is sensitive to hydrazine hydrate that is used to remove the phthaloyl group. 27 28 jV -Z-Protected a-aminoacylimidazoles, which are reduced to the corresponding aldehydes using lithium aluminum hydride, are extremely moisture sensitive and readily decomposed. 25 The catalytic reduction of mixed carbonic/carboxylic acid anhydrides, prepared from acylated a-amino acids, leads to poor reproducibility and low yields. 24 The major problems associated with these techniques are overreduction, racemization, and poor yields. 

Horner-Emmons reaction of N-terminal blocked aldehyde 1 with sulfonylphosphonates in the presence of sodium hydride gives the amino acid vinyl sulfone 2, which is deprotected with acid and converted into its chloride or tosylate salt 3 and coupled by the mixed anhydride method with an N-terminal protected peptide or amino acid to give the desired peptide vinyl sulfones 4 (Scheme 2). 4 5 N-Terminal protected aldehydes 1 are obtained from reduction of Boc amino acid V-methoxy-A-methylamides (Weinreb amides, see Section 15.1.1) by lithium aluminum hydride. 9 The V-methoxy-V-methylamide derivatives are prepared by reaction of Boc amino acids with N,O-dimethylhydroxylamine hydrochloride in... 

Apart from the reaction of diazomethane with benzoyl chloride,5-6 diazoacetophenone has been prepared by the reaction of 2-aminoacetophenone hydrochloride with sodium nitrite,7 from the mixed anhydride of benzoic acid and ethyl carbonate with diazomethane,8 from benzoyl chloride and potassium methyldiazotate,9 by treating the enamine formed from 2-formylacetophenone and N-methylaniline with p-toluenesulfonyl azide,10 and from the reaction of the sodium enolate of 2-formylacetophenone with p-toluenesulfonyl azide.11... 

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