Malonyl chloride, acylation with

Malonyl chloride reacted with boiling acetone to give the bicyclic 2 1 adduct 210 comprising a pyranone and a l,3-dioxan-4-one moiety (Scheme 99). The modest yield was compensated for by the ease of its preparation. Compound 210 bears a chloride which is almost as reactive as an acyl chloride and which can be substituted by various nucleophiles in a Stille coupling in modest yields <1997SL895>. Treatment of malonyl chloride with ketene and acetone at low temperature afforded symmetric bis(l,3-dioxin-4-ones) in 60% yield although a different reaction pathway may be assumed (Scheme 99) <2000TL4959>. 

Aminothiazole, with acetaldehyde, 42 to 2-mercaptothiazoie, 370 4-Aminothiazole-2,5-diphenyl, to 2,5 di-phenyl-A-2-thiazoline-4-one, 421 Ammothiazoie-A -oxide, 118 2-Aminothiazoles. 12 acidity of, 90 and acrylophenone, 42 acylations of, with acetic acid. 53 with acetic anhydride, 52 with acyl halides, 48 with chloracetyl chloride, 49 with-y-chlorobutyrylchloride, 50 with 0-chloropropionylchloride, 50 with esters, 53 with ethy acrylate, 54 with indoiyl derivatives, 48 with malonic esters, 55 with malonyl chloride, 49 with oxalyl chloride, 50 with sodium acetate, 52 with unsaturated acyl chloride, 49 additions to double bonds, 40 with aldehydes, 98 alkylations, with alcohols, 38 with benzyhydryl chloride, 34 with benzyl chloride, 80 with chloracetic acid, 33 with chloracetic esters, 33 with 2-chloropropionic acid, 32 with dialkylaminoalkyl halides, 33 with dimethylaminoethylchloride, 35 with ethylene oxide, 34, 38... 

Polystyrene can be cross-linked by its acylation with bifunctional acylating agents such as adipoyl, sebacoyl, or malonyl chlorides ia the presence of AlCl iu CS2 solution at 0°C (106). 

The cyclizations to obtain cyclic thioureas have been performed using thiocarbonyldiimidazole.232 Reaction of methyl acetoacetate, thiourea and an aliphatic aldehyde in the presence of the zinc iodide (Znl2) was studied. Under the normal pressure, reaction has not been occurred whereas at high pressure (300 MPa) conditions 3,4-dihydropyrimidine-2-thione was obtained only in 10% yield.233 The same one-pot three-component cyclocondensation reaction in the presence of iodide (I2) provides a variety of 3,4-dihydropyrimi-dine-2-thione in high yields.234 Condensation reaction of thioureas with a,p-unsaturated ketones in the presence of the sodium methoxide in methanol affords 3,4-dihydropyrimidine-2-thione derivatives.235,236 Acylation of N,N -disubstituted thioureas with methyl malonyl chloride followed by base-catalysed cyclization leads in the formation of l,3-disubstituted-2-thiobarbituric acids (Scheme 78).237... 

In an effort to circumvent this difficulty, a situation encompassing an intramolecular aldol condensation was envisioned. To this end, the model methoxypropio-phenone (88) was acylated with malonyl monoacid chloride mono ethyl ester, and... 

More recently, the reaction of malonyl chloride with the enol ethers of cyclic alkenes to give 4,6-alkano-1,3,5-trihydroxybenzene systems in variable yields (18-70%)(ref.2) has been investigated. For example, the enolic methyl ether of cyclooctene gives with malonyl chloride the phloroglucinol depicted by acylation at the double bond and allylic position. 

In contrast to the reaction of pristinamycin 11 with acid anhydrides, where acylation was only observed with acetic anhydride, the reaction of pristinamycin IIa with acid chlorides (Scheme 10) was demonstrated to be of greater synthetic utility. However, the course of acylation depended strongly on the reactivity of the acid chloride. For example, the reaction of pristinamycin 11 with ethyl malonyl chloride in the presence of triethylamine or pyridine resulted in a quantitative conversion by tic into the ester (50, R = CH2C02Et, 60% isolated yield) whereas the use of more reactive acyl chlorides, for example ethyl chloroformate resulted in acylation of the 37-ketone function as its enol ether (see Sect. 5.4.2). If the acylation reagents were used in excess, a diacylated derivative pf the enol form of pristinamycin 11 (51) was obtained. 

Treatment of [ C]malonic acid with oxalyl chloride in the presence of catalytic amounts of DMF affords [ C]malonyl chloride in nearly quantitative yield. The structure of the reagent was confirmed by acylation of 2-methoxypropene, which provided a 3 1 mixture of phloroglucinol monomethyl ether (428) and 4-hydroxy-6-methyl-2//-[2,4- " C]pyran-2-one (427). Etherification of the latter with dimethyl sulfate followed by ring opening upon treatment with sodium methoxide and recychzation afforded 429, which was combined with the original portion of 428 and etherified to give 1,3,5-trimethoxy-[1,3,5- C]benzene, which was used as a key intermediate in the synthesis of several carbon-14 labeled cholesterol acyltransferase inhibitors . ... 

Enediynes 3.798 also with a fused p-lactam ring but now with the nitrogen atom as part of the ten membered ring [218, 220] were synthesized by carbene insertion in diazo enediyne 3.797 in 50% yield (Scheme 3.97) [26, 369-371]. This was prepared by acylation of amine 3.795 with ethyl malonyl chloride in the presence of triethylamine to give amide 3.796, followed by the treatment with p-toluene sulfonyl azide on potassium carbonate as solid support. Treatment of solution of the diazo enediyne product 3.797 with a catalytic amount of rhodium acetate for 30 minutes resulted in the lactam-fused enediyne as the only isolable product. 

Diketones are converted into pyranones on treatment with malonyl dichloride, involving both C- and O-acylation (63JCS4483). The reaction between benzoylacetone and the acid chloride gives only one pyranone in accordance with a preferred direction of enolization consequent upon the unsymmetrical nature of the diketone a 5-acetyl-6-phenylpyranone results rather than the 5-benzoyl-6-methyl isomer. There is still some uncertainty as to whether the product is the 4-hydroxypyran-2-one (409) or the tautomer, but the former is considered to be the more likely. There is yet further controversy, since... 

Acylation of 1-acetylindole in the presence of aluminium chloride goes cleanly at C-6, but with diacid chlorides (malonyl, succinyl), 2-substitution occurs. The former result is due to strong deactivation of C-5 by a 1-acetyl-Lewis-acid complex and the latter is probably due to complexation of one acid chloride to the 1-acetyl group, followed by intramolecular delivery of the other. ... 

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