Chlorides, acyl reagents

The neutralized amine groups did not react with the acyl chloride reagents in the interfacial reaction step and did not undergo condensation reactions during the heat cure step of membrane formation. 

This chapter focuses on the advantages achieved with different procedures and makes comparative analyses of the synthetic results. Furthermore, despite utility at small scale, the use of Lewis acid/acyl chlorides reagents on an industrial scale is frequently discouraged due to the large amounts of waste produced. Practically, the use of homogeneous Lewis acids in combination with acyl chlorides or anhydrides poses a serious problem for the efficient recovery and disposal of metal oxides and protic inorganic acid by-products. 

Diethylcarbamyl chloride added at once to a dry soln. of pyridine N-oxide in benzene, then a soln. of -butyl mercaptan in triethylamine added slowly with cooling during 20 min., and refluxed 2 hrs. -> 2-n-butylthiopyridine. Y 67%. F. e. and acyl chloride reagents s. L. Bauer, T. E. Dickerhofe, and K.-Y. Tsemg, J. Heterocyclic Chem. 12, 797 (1975). 

In synthetic target molecules esters, lactones, amides, and lactams are the most common carboxylic acid derivatives. In order to synthesize them from carboxylic acids one has generally to produce an activated acid derivative, and an enormous variety of activating reagents is known, mostly developed for peptide syntheses (M. Bodanszky, 1976). In actual syntheses of complex esters and amides, however, only a small selection of these remedies is used, and we shall mention only generally applicable methods. The classic means of activating carboxyl groups arc the acyl azide method of Curtius and the acyl chloride method of Emil Fischer. 

The acylstannanes 874 and 875 are prepared by the reaction of acyl chlorides with (MciSnl - The symmetrical 1,2-diketones 877 can be prepared by the reaction of an excess of benzoyl chloride with (EtjSn) . Half of the benzoyl chloride is converted into the benzoyltin reagent 876, which is then coupled with the remaining benzoyl chloride under a CO atmosphere to afford the a-diketone 877[748], Triethyl phosphite is used as a ligand. 

Treating the iminothiazoles with acyl chlorides yields the aminium salts (415>, which are acylation and alkoxycarbonylation reagents (Scheme 237) (731). 

The characteristic reaction of acyl chlorides acid anhydrides esters and amides is nucleophilic acyl substitution Addition of a nucleophilic reagent Nu—H to the carbonyl group leads to a tetrahedral mtermedi ate that dissociates to give the product of substitution... 

Section 20 6 Acid anhydrides are less reactive toward nucleophilic acyl substitution than acyl chlorides but are useful reagents for preparing esters and amides... 

CoupDng of ongarxjtin reagents (and Pd catalyst) with aryl or vinyl haiidas or triflates, acyl chlorides or allyl acetates. 

There are some problems associated with the use of functional derivatives of carboxylic acids. Long-chain acid anhydrides are not commercially available, and one half of the acylation reagent is not utilized. Acyl chlorides require the use of tertiary base catalysts, whose double role has been explained before. Some of the intermediate acyl ammonium compounds formed are, however, insoluble in the solvent system. Examples include RCO - N+EtsCL in LiCl/DMAc, where RCO refers to the propionyl, hexanoyl, and stearoyl moiety, respectively. Hexanoyl- and stearoyl-pyridinium chlorides are also insoluble in the same solvent system [185]. 

Nucleophilic addition reactions of allylic tin reagents to chiral 3-substituted 3,4-dihydroisoquinolines 89 activated by acyl chlorides afford trans 1,3-disubstituted 1,2,3,4-tetrahydroisoquinolines 90 stereoselectively <95CL1003>. 

This reagent combination also converts carboxylic acids to acyl chlorides (see Section 3.4.1). The mechanistic basis for the special effectiveness of benzotriazole has not yet been determined, but it seems likely that nucleophilic catalysis is involved. Sulfinyl ester intermediates may be involved, because Z-2-butene-l,4-diol gives a cyclic sulfite ester with one equivalent of reagent but the dichloride with two equivalents. 

The inclusion of DMAP to the extent of 5-20 mol % in acylations by acid anhydrides and acyl chlorides increases acylation rates by up to four orders of magnitude and permits successful acylation of tertiary and other hindered alcohols. The reagent combination of an acid anhydride with MgBr2 and a hindered tertiary amine, e.g., ( -Pr)2NC2H5 or 1,2,2,6,6,-pentamethylpiperidine, gives an even more reactive acylation system, which is useful for hindered and sensitive alcohols.105... 

Ketones can also be prepared from acyl chlorides by reaction at low temperature using an excess of acyl chloride. Tetrahydrofuran is the preferred solvent.91 The reaction conditions must be carefully controlled to prevent formation of tertiary alcohol by addition of a Grignard reagent to the ketone as it is formed. 

Pyridinethiolate esters, which are easily prepared from acyl chlorides, also react with Grignard reagents to give ketones (see Entry 6 in Scheme 7.3).92 /V-Mclhoxy-/V-mclhylamides are also converted to ketones by Grignard reagents (see Entries 17 and 18). 

Lewis acids catalyze the reaction of alkylzinc reagents with acyl chlorides.160 The reaction is also catalyzed by transition metals, as is discussed in Chapter 8. 

The most common application of organocadmium compounds has been in the preparation of ketones by reaction with acyl chlorides. A major disadvantage of the use of organocadmium reagents is the toxicity and environmental problems associated with use of cadmium, and this has limited the recent use of organocadmium reagents. 

Organomercury reagents do not react with ketones or aldehydes but Lewis acids cause reaction with acyl chlorides.187 With alkenyl mercury compounds, the reaction probably proceeds by electrophilic attack on the double bond with the regiochemistry being directed by the stabilization of the (3-carbocation by the mercury.188... 

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