Reactions involving acid chlorides

Comments Many reactions involving acid chlorides include a basic catalyst. Burden et al. [15], however, observed some enantioselectivity in incomplete reactions when either 4-dimethylaminopyridine or N-methylimi-dazole was added to the reaction mixture. 

The stereoselectivity of the reaction of ketenes with imines to produce -lactams depends upon the method of ketene generation and different results are obtained in reactions involving acid chloride/NEt versus the photolysis of chromium carbene complexes. ) The complex Cr sC(CH2)2CHMeO (CO)s and aliphatic aldehydes RiR CHCHO bearing a-hydrogen atoms, in... 

The submitters have shown that these reactions proceed by dehydro-chlorination of the acid chloride to the ketene, which is then trapped by reaction with the phosphorane. The resulting betaine decomposes to the allenic ester via an oxaphosphetane. In contrast, the reaction of acid chlorides with 2 equivalents of phosphoranes involves initial acylation of the phosphorane followed by proton elimination from the phosphonium salt. ... 

Acid chlorides, RCOCl, undergo ready attack by weaker nucleophiles, e.g. H2O, ROH. The question then arises whether, with the better potential leaving group Cl , the reactions of acid chlorides could proceed either via a single step 8 2 type pathway (cf. p. 78) involving a T.S., in which attack by and loss of Q are essentially synchronous or via an 8 1 type pathway (cf. p. 79) in which the slow step is RCOCl RCO Cl , followed by fast attack by Y on the acyl cation, RCO . In fact, most reactions of acid chlorides probably proceed via the now familiar tetrahedral intermediate pathway, though there may be some exceptions. 

The synthesis of the moxifloxacin core (de Souza, 2006 Martel et al., 1997 Seidel et al., 2000) proceeds from a Grohe-Heitzer sequence as described earlier in the chapter. Unlike the traditional Grohe-Heitzer sequence, however, the opening step involved the reaction between acid chloride 101 with the mono potassium salt of malonic acid monoethyl ester (102) in the presence of triethylamine to deliver ketoester 103 (Scheme 4.18). Treatment of 103 with ethyl orthoformate furnished acrylate 104, which reacted with cyclopropyl amine to afford 105. Cyclization of 105 in the presence of sodium fluoride in DMF gave the moxifloxicin core 106. 

The mechanism of the Friedel-Crafts acylation reaction, formulated below for reactions using acid chlorides, probably involves the acylium ion (2) as the reactive electrophilic species, although an electrophilic complex (1) between the acid chloride and aluminium chloride may also be involved. 

Reactions of Acid Chlorides Acid chlorides react quickly with water and other nucleophiles and are therefore not found in nature. Because they are the most reactive acid derivatives, acid chlorides are easily converted to other acid derivatives. Often, the best synthetic route to an ester, anhydride, or amide may involve using the acyl chloride as an intermediate. 

Acylation. Aromatic acyclation processes are widely applied in the fine chemical industry as reaction steps in the synthesis of pharmaceuticals and fragrances. Present day industrial synthesis generally involves acid chlorides as the acylating agent. Due to the strong coordination of the product ketone to the Lewis-acid "catalyst" (A1C13,... 

Two different synthetic routes to polyesters are through the reaction of glycols or other polyfunctional hydroxy-compounds emd anhydrides such as phthalic anhydride, and by the reaction of acid chlorides with glycols or bisphenols. These two reactions may be regarded as irreversible. In the case of polyester-forming reactions that involve the use of acid chlorides (Section 5.7), the reaction proceeds better when the hydrochloric acid produced in the polycondensation is effectively removed, by neutralization, for example. 

Two reports involving reactions of acid chlorides with stannylfurans have appeared [90,91]. 

The most important side-chain conversion involves reduction of ketones either by amalgamated zinc and HCl (Clemmensen reduction) or by hydrazine and strong base Wolff-Kishner reduction). This method is important because the necessary ketones are readily available through a modification of the Friedel-Crafts reaction that involves acid chlorides (see Sec. 19.6). Unlike alkylation by the Friedel-Crafts reaction, this method does not involve rearrangement. 

Sulfamide (136) may be used in the synthesis of nitriles (148) by a one-pot reaction with acid chlorides involving elimination of sulfamic acid (86) (Scheme 60). The reaction is believed to involve the initial formation of the N-acylsulfamide followed by enolisation and subsequent elimination of sulfamic acid (86) (Scheme 60). 

Reaction with acid chlorides.2 The adduct reacts with aliphatic and aromatic acid chlorides to give phosphate esters of a-hydroxy /3-diketones (1) in yields of 70-90%. The reaction is considered to involve nucleophilic substitution at the carbonyl group of the acid chloride. The esters are hydrolyzed to a-hydroxy-/3-di-ketones readily by refluxing aqueous benzene (12 hrs.). 

Reaction of Acid Chlorides. Low-temperature polycondensation of diamines and diacid chlorides is an important route for preparing high-melting polyamides such as aromatic polyamides, which decompose or cross-link if prepared by high-temperature melt routes. The reaction may involve an interfacial reaction between the diacid chloride in a water-immiscible solvent with an aqueous diamine solution, or the reaction may be carried out in a homogeneous solution. The presence of a base is usually needed to remove HCl so that polymerization is complete. With weakly basic aromatic diamines, an acid acceptor is not always needed because HCl can be evaporated from the reaction mixture. The general reaction is given by... 

Many examples of the usual route to /S-lactams via imines and acid chlorides, ketens, or keten equivalents have appeared.These include syntheses of 3-[bis(alkylthio)methylenamino]-2-azetidinones, ° of spiro-azetidinones and bis-azetidinones, and the use of l-methyl-2-halogenopyridinium salts to activate carboxylic acids towards coupling with imines. A non-hazardous alternative route to 3-amido-2-azetidinones, avoiding the use of azidoacetyl chloride, involves the reaction of Schiff bases with salts of [(a-methyl-/3-methoxycar-bonyl)vinylamino]acetic acid, e.g. (20), in the presence of ethyl chloroformate, as shown in Scheme 5. Formaldimines can be generated from their trimers by treatment with Lewis acids immediately prior to reaction with acid chlorides, so allowing the formation of the nocardicin nucleus which is unsubstituted at C-4. ... 

How many grams of sodium chloride are required to synthesize 73 grams of hydrogen chloride, if the reaction involves sodium chloride and sulfuric acid ... 

An alternative route involves the reaction of acid chloride and amine at low temperatures to form high-melting polyamides ... 

Most reactions of alkenylsilanes require strong carbon electrophiles, and Lewis acid catalysts are often involved. Reaction with acid chlorides is catalyzed by aluminum chloride or stannic chloride. ... 

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