A mild, clean, and simple synthesis of symmetrical carboxylic anhydrides from carboxylic acides using a polymer supported tosyl chloride

The use of polymeric reagents simplifies routine acylation of carboxylic acid because it eliminates the traditional purification. We describe the use of readily available cross-linked poly(4-vinylpyridine) supported tosyl chloride, [P₄VP].TsCl, in the suspended solution phase synthesis of symmetrical anhydrides from carboxylic acids in the presence of K₂CO₃ in high yields and purity. The products can be obtained by filtration and evaporation of the solvent.     

A facile synthesis of alkyl substituted maleic anhydrides: radical approach

Synthetic background for the preparation of alkyl substituted maleic anhydrides and maleimides based on radical alkylation of 2,3-dichloromaleic anhydride (maleimide) by hydrocarbons was developed. The best conditions for the selective synthesis of 2-alkyl-3-chloro- and unsymmetrically substituted dialkylmaleic anhydrides were elaborated.     

A new synthesis of carboxylic and carbonic acid anhydrides using phase transfer reactions

Acyl chlorides and alkylchloroformates smoothly reacted with one molar equivalent of sodium hydxoxide, using liquid-liquid phase transfer conditions to afford high yields of the corresponding symmtrical carboxylic and carbonic hemiester anhydrides. Unstable, anhydrides such as 4-nitrobenzoïc, 2-furoïc and methacrylic anhydrides, which are otherwise difficult to obtain, were easily prepared by this method. The reaction mechanism does not seem to involve intermediate hydrolysis of half the acid chloride into the corresponding sodium carboxylate.     

A facile synthesis of 4-oxo carboxylic acids from γ-butyrolactone.

An efficient, high-yield, three-step preparation of 4-oxo carboxylic acids from γ-butyrolactone via silylation and reaction with a Grignard reagent is presented.     

New facile and mild synthesis of 2-substituted oxazolopyridines

A new, two-step synthesis of oxazolopyridines is described. The synthesis involving amide formation between o-aminopyridinols and aliphatic or aromatic carboxylic acids followed by condensation with hexachloroethane/triphenylphosphine takes place at room temperature and thereby gives mild access to all regioisomeric, 2-substituted oxazolopyridines in good yields.     

A facile synthesis of primary amines from carboxylic acids by the curtius rearrangement

2-Trimethylsilylethanol was used to trap isocyanates produced by the Curtius rearrangement of acyl azides and the resulting trimethylsilylethyl carbamates were readily cleaved with tetra-n-butylammonium fluoride to liberate the primary amines.     

A facile access to natural and unnatural dialkylsubstituted maleic anhydrides

A facile new route to the potential building blocks 2-bromomethyl-3-alkylmaleic anhydrides 15a/b for the synthesis of natural and unnatural dialkylsubstituted maleic anhydrides has been demonstrated, starting from dimethyl citraconate (9) via NBS-bromination, S_N2′ Grignard coupling reactions, hydrolysis, molecular bromine addition and dehydrative ring closure reactions pathway with 49-51% overall yield in 5-steps. Chemoselective allylic substitution of bromoatom in 15a/b with Grignard reagents has been described to obtain the unsymmetrical maleic anhydride 16 and symmetrically dialkylsubstituted maleic anhydrides 25a/b in 55% yield. The naturally occurring 2-carboxymethyl-3-hexylmaleic anhydride (1) has been synthesized from 16 via esterification, ozonolysis and an oxidation route. The synthesis of two naturally occurring 2-(β-carboxyethyl)-3-alkylmaleic anhydrides 2a/b have been completed via a chemoselective diethylmalonate coupling reaction followed by acid induced hydrolysis. In our hands the S_N2 or S_N2′ coupling of Grignard reagent with 21 to obtain 1 and Reformatsky reaction with 15a/b to obtain 2c/d met with failure.     

Samarium-mediated mild and facile method for the synthesis of amides

Samarium-mediated facile method for the formation of amide bonds by the reaction of acyl chlorides and amines is described. The reaction afforded high yields of the desired amides under mild and neutral conditions.     

Indium-mediated mild and facile method for the synthesis of amides

Indium-mediated coupling reactions of acyl chlorides and amines for the synthesis of amide bonds are described. The reaction afforded high yields of the desired amides under mild and neutral conditions, and it was applicable also to the preparation of peptides without epimerization.     

Zinc(0)/dimethylformamide-mediated synthesis of symmetrical carboxylic anhydrides from acid chlorides

The high yielding synthesis of symmetrical carboxylic anhydrides from acid chlorides mediated by zinc dust in the presence of dimethylformamide is presented. A mechanism involving the reductive insertion of zinc(0) into the C-Cl bond of a Vilsmeier-type iminium intermediate as the crucial step is also proposed.     

A mild method for the synthesis of 2-ketopyrroles from carboxylic acids

A mild method for the synthesis of 2-ketopyrroles from carboxylic acids via 2-pyridylthiolesters and pyrrylmagnesium chloride is described.     

A facile and mild method for the synthesis of terminal bromofluoroolefins via diethylzinc-promoted Wittig reaction

[reaction: see text] Synthesis of 1-bromo-1-fluoroolefins was achieved in good yields via a Wittig reaction promoted by diethylzinc, even with nonactivated aldehydes and ketones as starting materials.     

A mild and efficient catalytic alkylative monofunctionalization of cyclic anhydrides.

Substituted succinic and glutaric anhydrides undergo a nickel-catalyzed monofunctionalization with organozinc reagents as nucleophiles. The reaction proceeds readily with a variety of substrates, employs commercially available or readily attainable reagents, tolerates sensitive functionality on both partners, and affords the product ketoacids in moderate to high yields. The use of a chiral phosphinooxazoline results in a desymmetrization of a meso anhydride to provide the ketoacid in 85% yield and 79% ee.     

Reaction of essentially free benzyl cations with acetonitrile; synthesis of ethanimidic carboxylic anhydrides and unsymmetrical diacylamines

Benzyl cations were generated via the thermal decomposition of N-benzyl-N-nitrosopivalamide in acetonitrile and acetonitrile-water mixtures at 25 degrees C. The first-formed (primary) benzylating agent, the benzyl cation, was scavenged competitively by pivalate (trimethyl acetate) ion to yield benzyl pivalate, by acetonitrile to yield the corresponding N-benzylnitrilium ion, and by water (when present) to yield benzyl alcohol. The nitrilium ion underwent a cascade of reactions to yield an array of products whose identities and relative yields as a function of time were used to elucidate the mechanistic paths involved. Thus, the N-benzylnitrilium ion reacted with pivalate ion to yield the Z-isomer of N-benzylethanimidic pivalic anhydride, followed by its conversion into the E-isomer. This article appears to be the first to document compounds of this type. The E-isomer is labile under the reaction conditions, rearranging into N-acetyl-N-pivalylbenzylamine. In the presence of water as a diluent, a significant fraction of the nitrosoamide was hydrolyzed to benzyl alcohol; hydrolysis of the nitrilium ion yielded N-benzyl acetamide. The yield of hydrosylates was directly proportional to the mole fraction of water in the medium.     

A mild and efficient one pot synthesis of 1,3,4-oxadiazoles from carboxylic acids and acyl hydrazides

A convenient one pot method for the synthesis of 2,5-disubstituted 1,3,4-oxadiazoles from acids and acyl hydrazides is reported. Acid activation with CDI, followed by coupling with the desired acylhydrazide and dehydration in the same pot with Ph₃P and CBr₄ affords the corresponding 1,3,4-oxadiazoles in good yield. The scope of the acid and acylhydrazide components is presented.