Carboxylic acids acid chlorides

Aldehydes, ketones, carboxylic acids, acids chlorides, esters and epoxides to the corresponding alcohols. 

Acyl-transfer reactions are some of the most important conversions in organic chemistry and biochemistry. Recent work has shown that adjacent cationic groups can also activate amides in acyl-transfer reactions. Friedel-Crafts acylations are known to proceed well with carboxylic acids, acid chlorides (and other halides), and acid anhydrides, but there are virtually no examples of acylations with simple amides.19 During studies related to unsaturated amides, we observed a cyclization reaction that is essentially an intramolecular acyl-transfer reaction involving an amide (eq 15). The indanone product is formed by a cyclization involving the dicationic species (40). To examine this further, the related amides 41 and 42 were studied in superacid promoted conversions (eqs 16-17). It was found that amide 42 leads to the indanone product while 41... 

Fig. 15.22 Display of predicted Hansch parameters of the sum of inductive and resonance constants (F + R) versus lipophilicity (jr) for 302 commercially available carboxylic acids, acid chlorides, sulphonyl chlorides and isocyanates. Symbol size corresponds to larger molecular size (MR). Circles represent the selected R groups and triangles represent the unselected compounds. Colors convey the segmentation of the diversity reagents into nine sectors for selection.

However, the most important methods for preparing alcohols are catalytic hydrogenation (H2/Pd-C) or metal hydride (NaBH4 or LiAlH4) reduction of aldehydes, ketones, carboxylic acids, acid chlorides and esters (see Sections 5.7.15 and 5.7.16), and nucleophilic addition of organometalhc reagents (RLi and RMgX) to aldehydes, ketones, acid chlorides and esters (see Sections 5.3.2 and 5.5.5). 

The carboxylic acid derivatives vary greatly in their reactivities in the acyl substitution reactions. In general, it is easy to convert more reactive derivatives into less reactive derivatives. Therefore, an acid chloride is easily converted to an anhydride, ester or amide, but an amide can only be hydrolysed to a carboxylic acid. Acid chlorides and acid anhydrides are hydrolysed easily, whereas amides are hydrolysed slowly in boiling alkaline water. 

Carboxylic acids, acid chlorides, acid anhydrides and esters get reduced to primary alcohols when treated with lithium aluminium hydride (LiAlH) (Fig.M). The reaction involves nucleophilic substitution by a hydride ion to give an intermediate aldehyde. This cannot be isolated since the aldehyde immediately undergoes a nucleophilic addition reaction with another hydride ion (Fig.N). The detailed mechanism is as shown in fig.O. 

Lithium aluminium hydride is highly reactive and can also reduce carboxylic acids, acid chlorides, anhydrides, esters, lactones, amides, lactams, imines, nitriles and nitro group. For example, -COCI, -CO2H, -C02Et, -CHO and >CO are reduced to -CH2OH or >CHOH, provided the correct solvent is used. 

These include carboxylic acids, acid chlorides, esters, and amides, as well as other similar compounds discussed in Chapter 22. Each of these compounds contains an electronegative atom (Cl, O, or N) capable of acting as a leaving group. Acid chlorides, esters, and amides are often called carboxylic acid derivatives, because they can be synthesized from carboxylic acids (Chapter 22). 

Until about 1950, reduction of carboxylic acids and their derivatives to aldehydes was not straightforward, and even one of the best methods, the Rosenmund hydrogenation of acid chlorides, required very careful control of both the reaction conditions and preparation of catalyst. The advent of aluminum and boron hydrides and their ready commercial availability transformeKl the situation to such an extent that the formation of aldehydes from carboxylic acids, acid chlorides, esters, amides, nitriles and similar groups in the presence of other reducible functional groups has become a relatively easy operation on both small and large scale. 

Based on the carboxylic acid, acid chloride, or alkyl halide. 

Functional group priorities carboxylic acid > acid chloride > aldehyde > nitrile > ketone > alcohol > amine > halide... 

After attaching the chloroacetic acid derivatives, they can be converted to the carboxylic acid, acid chloride, and finally to the amide functions (Takada et al., 1988). A shorter process (bottom reaction in scheme above) used chloroacetonitrile followed by reduction instead of chloroacetate to give the product in an overall yield of 76% (Dietrich et al., 1989). Chloroacetonitrile was previously used to prepare secondary amines from primary amines (Overman and Burk, 1984). 

Carboxylic acids, acid chlorides, acid anhydrides and esters... 

Selective reductions. The reducing properties of 9-BBN in THF have been nviewed in detail. Aldehydes and ketones are reduced rapidly and in high yield th some bias, in the case of unsymmetrical ketones, for attack from the less hindered side. a,)3-Unsaturated aldehydes and ketones are reduced selectively to tilylic alcohols. Anthraquinone (1) is reduced cleanly to 9,10-dihydro-9,10- nthracenediol (2). Carboxylic acids, acid chlorides, and esters are reduced I Afflciently. Epoxides are reduced only slowly by 9-BBN, but are reduced readily... 

Carboxylic acids, acid chlorides, and acid anhydrides react with alcohols to produce esters, objective 6 (Section 5.5), Exercise 5.36 Polyesters result from the reaction of dicar-boxylic acids and diols. Polyesters are an example of condensation polymers these are produced when monomers react to form a polymer plus a small molecule such as water. Many esters are very fragrant and represent some of nature s most pleasant odors. Because of this characteristic, esters are widely used as flavoring agents. 

Esterification (Section 17.7A) The synthesis of an ester, usually involving reactions of carboxylic acids, acid chlorides or acid anhydrides with alcohols. 

Ionic compounds are usually scarcely soluble, but covalent compounds such as hydrogen halides and many organic compounds are soluble. Examples are hydrocarbons, carboxylic acids, acid chlorides, nitriles, aldehydes, ketones, alcohols, amines and nitrocompounds, but the conductivities of their solutions are very small. Many acceptor halides such as those of aluminium, titanium(IV), tin(IV), phosphorus(V), arsenic(III) and bismuth(III) as well as ferric chloride show reasonable solubilities due to interaction with liquid hydrogen sulphide. Solvates of AICI3, AlBrs, TiCl4, SnCU, BCI3 and others have been described . 

Anhydrides of carboxylic acids are, as the name suggests, the product of two carboxylic acid units that couple together with loss of water. It is possible to convert carboxylic acids directly to anhydrides, but more commonly they are prepared from acid chlorides. Once an acid chloride has been prepared, it is highly reactive in the presence of a variety of nucleophiles, even relatively weak nucleophiles. In Section 20.2, for example, the reaction of an acid chloride with water gave the parent carboxylic acid. Acid chlorides react with other carboxylic acids to form anhydrides where the acid behaves as a nucleophile. 

Thus far, the chapter has been devoted to the chemistry of carboxylic acid derivatives. Another important class of organic acids is the sulfonic acids (see 175 X = OH). In principle, sulfonic acids should give the same t3rpes of derivatives as the carboxylic acids acid chlorides, esters, and amides. This section will explore some of these common sulfonic acid derivatives sulfonyl chlorides (175 ... 

Section 32 Alcohols and Phenols from Carboxylic Acids, Acid Chlorides and... 

ALCOHOLS AND PHENOLS FROM CARBOXYLIC ACIDS, ACID CHLORIDES AND ANHYDRIDES... 

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