Acyl halides reactions with ethanol

When the reagent is the thiocyanate ion, S-alkylation is an important side reaction (10-43), but the cyanate ion practically always gives exclusive N-alkylation. ° Primary alkyl halides have been converted to isocyanates by treatment with sodium nitrocyanamide (NaNCNN02) and m-chloroperoxybenzoic acid, followed by heating of the initially produced RN(N02)CN. ° When alkyl halides are treated with NCO in the presence of ethanol, carbamates can be prepared directly (see 16-7). ° Acyl halides give the corresponding acyl isocyanates and isothiocyanates. For the formation of isocyanides, see 10-111. 

There is also evidence for the role of acylium ions in some acyl substitutions, such as the reactions of acyl halides with nucleophilic reagents in acetonitrile, nitromethane, and ethanol and the hydrolysis of some acyl fluorides. 203,206,207 ylium ions are more likely candidates for reaction intermediates under acidic conditions. Bender reported that the hydrolysis of a series of substituted methyl 2,6-dimethylbenzoates in 9.7 M sulfuric acid proceeds through an acylium ion intermediate. Hydrolysis of a series of substituted 2,6-dimethylbenzoyl chlorides in 99% CH3CN-H2O was determined to involve an acylium intermediate under acidic or neutral conditions, and p values (measured by cr" ) were found to be -3.85 and -3.73, respectively. The value of p under basic conditions was -I-1.20, suggesting that the base-promoted reaction does involve a tetrahedral addition intermediate. ... 

Stirring these acyl compounds with a base such as sodium ethoxide in dry ethanol solution. The presence of an electron-withdrawing substituent appears to drastically decrease the rate a complex di-p-chloro-bis[MA -dimethyl-5-chlorobenzylamino-2C,Andipalladium(ll) is recovered unchanged after 3 days under reflux under the same reaction conditions. These reactions are presumed to proceed through a two-step process in which the first step is the insertion of acyl halides and the second is the potassium cyanide-induced dissociation of the presumed intermediates 7.37 [76,88]. 

Concurrent with acetic anhydride formation is the reduction of the metal-acyl species selectively to acetaldehyde. Unlike many other soluble metal catalysts (e.g. Co, Ru), no further reduction of the aldehyde to ethanol occurs. The mechanism of acetaldehyde formation in this process is likely identical to the conversion of alkyl halides to aldehydes with one additional carbon catalyzed by palladium (equation 14) (18). This reaction occurs with CO/H2 utilizing Pd(PPh )2Cl2 as a catalyst precursor. The suggested catalytic species is (PPh3)2 Pd(CO) (18). This reaction is likely occurring in the reductive carbonylation of methyl acetate, with methyl iodide (i.e. RX) being continuously generated. 

The cyclodehydration of readily available Af-phenacyl-A( -acylhydrazines (177) and related compounds, continues to provide a versatile entry to the 1,3,4-oxadiazine ring-system. Cyclodehydration, which usually yields the 4//-derivatives (178) can be effected with polyphosphoric acid and acetic acid at 140°C <83MI 6i7-0l>, or, as in the case of the benzoin iV-acyl hydrazones (179 X = OH), in good yields (75-80%) with polyphosphoric acid at 160°C <85IJC(B)979>. The 5,6-diphenyl-4//-1,3,4-oxadiazines (180) resulting from this latter reaction are also available, but in lesser yields (50-60%), by condensation of desyl halides (179 X = Cl or Br) with an acylhydrazide (RCONHNHj) followed by cyclization in hot ethanolic potassium hydroxide. 

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