Acid chlorides addition-elimination reaction

Rates and product selectivities 5 = ([ester product]/[acid product]) x ([water]/ [alcohol solvent] were reported for solvolyses of chloroacetyl chloride at —10 °C and phenylacetyl chloride at 0 °C in EtOH- and MeOH-water mixtures. Additional kinetic data were reported for solvolyses in acetone-water, 2,2,2-trifluoroethanol (TFE)-water, and TFE-EtOH mixtures. Selectivities and solvent effects for chloroacetyl chloride, including the kinetic solvent isotope effect (KSIE) of 2.18 for MeOH, were similar to those for solvolyses of p-nilrobcnzoyl chloride rate constants in acetone-water were consistent with a third-order mechanism, and rates and products in EtOH-and MeOH-water mixtures could be explained quantitatively by competing third-order mechanisms in which one molecule of solvent (alcohol or water) acts as a nucleophile and another acts as a general base (an addition-elimination reaction channel) (29 R = Et, Me, H).23... 

This is an addition -elimination reaction involving addition of methylamine to the acid chloride and elimination of hydrochloric acid. The mechanism is illustrated below using arrow pushing. 

The reaction between salicylic acid and acetyl chloride is an addition-elimination reaction where the hydroxyl group of salicylic acid adds to the carbonyl of acetyl chloride. This addition is followed by the elimination of hydrochloric acid as shown below. 

Amides can be prepared in a variety of ways, starting with acyl chlorides, acid anhydrides, esters, carboxylic acids, and carboxylate salts. All of these methods involve nucleophilic addition—elimination reactions by ammonia or an amine at an acyl carbon. As we might expect, acid chlorides are the most reactive and carboxylate anions are the least. 

The alcohol undergoes a nucleophilic addition-elimination reaction at the sulfonic acid group, with loss of chloride this generates a protonated sulfonate ester. Deprotonatlon by pyridine generates the product. 

Thionyl chloride Is electrophilic, and susceptible to attack by the carboxylic acid a sequence of addition-elimination reactions gives the corresponding acid chloride. 

The acid chlorides contain an excellent leaving group, and addition-elimination reactions are common (Fig. 17.44). 

FIGURE 18i22 Addition-elimination reactions of acid chlorides. Note the synthetic potential. 

Many nucleophiles are effective in the addition—elimination reaction of acid chlorides, and a great many acyl compounds can he made using acid chlorides as starting materials. 

The presence of the good leaving group (chloride) attached directly to the carbon-oxygen double bond makes all manner of addition-elimination reactions possible for acid chlorides. The acid chloride can be used to make anhydrides, esters, carboxylic acids, amides, aldehydes, ketones, and alcohols. 

In Section 16.5 we saw that in a nucleophilic addition-elimination reaction, the nucleophile that adds to the carbonyl carbon must be a stronger base than the substituent that is attached to the acyl group. This means that a carboxylic acid derivative can be converted into a less reactive carboxylic acid derivative in a nucleophilic addition elimination reaction, but not into one that is more reactive. For example, an acyl chloride can be converted into an ester because an alkoxide ion is a stronger base than a chloride ion. 

The most widely employed synthetic route to aramids is based on the polycondensation of dicarboxylic acids with diamines in the presence of condensing agents. Good reviews on the synthesis of aramids have recently appeared (1-3). Recently, promising alternative synthetic routes to aramids have been reported and are described herein. These include the polycondensation of N-silylated diamines with diacid chlorides, the addition-elimination reaction of dicarboxylic acids with diisocyanates, and the palladium-catalyzed carbonylation polymerization of aromatic dibromides, aromatic diamines and carbon monoxide. 

Several papers report on the nucleophilic reactivity of dithiocarbamate ions towards alkyl halides, 1,2-dibromoalkyl compounds, alkyl and aryl chloroformates, chloroacetic acid, chloroacetates, 3-halo-genophthalides, sulphenyl chlorides, sultones, and trialkylam-monium compounds. Examples of a similar reactivity of dithiocarbazate anions have also appeared. " A series of papers deal with addition or addition-elimination reactions of dithiocarbamate - or dithiocarbazate anions with w-nitrostyrene, 2-thioxo-, 2-oxo-, and 2-imino-5-methoxycarbonylmethylidene-4-thiazolidones, dimethyl acetylenedicar-boxylate, and NN -dialkyl phenylpropiolamidines. S-Monoalkylated N-cyanodithioimidocarbonates (492) underwent oxidative ring-closure to give 3-halogeno-l,2,4-thiadiazole sulphides (493) on treatment with halogenating agents. ... 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

Ion 21 can either lose a proton or combine with chloride ion. If it loses a proton, the product is an unsaturated ketone the mechanism is similar to the tetrahedral mechanism of Chapter 10, but with the charges reversed. If it combines with chloride, the product is a 3-halo ketone, which can be isolated, so that the result is addition to the double bond (see 15-45). On the other hand, the p-halo ketone may, under the conditions of the reaction, lose HCl to give the unsaturated ketone, this time by an addition-elimination mechanism. In the case of unsymmetrical alkenes, the attacking ion prefers the position at which there are more hydrogens, following Markovnikov s rule (p. 984). Anhydrides and carboxylic acids (the latter with a proton acid such as anhydrous HF, H2SO4, or polyphosphoric acid as a catalyst) are sometimes used instead of acyl halides. With some substrates and catalysts double-bond migrations are occasionally encountered so that, for example, when 1 -methylcyclohexene was acylated with acetic anhydride and zinc chloride, the major product was 6-acetyl-1-methylcyclohexene. ... 

Additional work was carried out by the GE group on optimization of the reaction yield and to eliminate unwanted linear oligomers [14], Three side reactions which interfere with synthesis of cyclics were identified reaction of the amine with acid chloride to form an acyl ammonium salt, followed by decomposition to an amide (Equation (3.2)) reaction with CH2CI2 to form a salt (Equation (3.3)) hydrolysis of the acid chloride, forming carboxylate via catalysis... 

Acylation reactions can also be greatly improved in this way, with t-alkyl- or sec-alkyl-manganese reagents reacting with acid chlorides in excellent yields [123]. The related addition-elimination to 3-ethoxy-2-cyclohexenone is also improved, resulting after acidic aqueous workup in 3-methyl-2-cyclohexenone [125]. The perilla-ketone 126 was prepared in an improved yield using copper(I) catalysis (Scheme 2.58) [129]. 

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