Acid chlorides leaving group

IfXis nitrogen then a direct method of animation results. The required reagent is a chloramine or the rather safer O-hydroxylaminesulfonic acid the leaving group is chloride or sulfonate. The overall... 

Stearolic acid better leaving group than chloride. 

Esters and acid chlorides react with Grignard reagents to form tertiary alcohols. The first mole of Grignard displaces the alkoxide or chloride leaving group to form a ketone. The ketone undergoes nucleophilic addition to form the tertiary alcohol. 

Phosphorus pentachloride is an electrophile, with excellent chloride leaving groups. The carboxylic acid reacts with PCI5 to give an acid chloride, via an activated phosphoryl intermediate. 

Benzene is a good nucleophile, by virtue of its ji-electron density. Alkyl chlorides are activated by the potent Lewis acid, aluminium chloride, to departure of the chloride leaving group, to give an intermediate carbocation. 

Reaction of a sulfonyl acid chloride with the alcohol nucleophile gives an ester product, in this case a sulfonate, with expulsion of a chloride leaving group. 

Mixed anhydrides can be formed by reaction of the acid chloride of one carboxylic acid with a different carboxylic acid in the presence of a base the mechanism involves the addition of the carboxylate nucleophile and elimination of the chloride leaving group from the resulting CTI. 

In the case of esters, carboxylate anions, amides, and acid chlorides, the tetrahedral adduct may undergo elimination. The elimination forms a ketone, permitting a second addition step to occur. The rate at which breakdown of the tetrahedral adduct occurs is a function of the reactivity of the heteroatom substituent as a leaving group. The order of stability of the... 

Acid chlorides, which have a very good leaving group (low basicity and nucleo-philicity), may react in this manner. 

Much less work has been done on the arylation of enamino ketones. The enamino ketone (49) has been allowed to react with 2,4,6-trinitrochloro-benzene. In this instance the latter reacts as the acid chloride of an acid the anion of which is a good leaving group (46). This type of reaction will be discussed in Section IV.A. 

As reagents concentrated sulfuric acid, hydrochloric acid, liquid sulfur dioxide, thionyl chloride, phosphorus pentachloride, zinc oxide" and even silica gel can be used. Reagents like phosphorus pentachloride (as well as thionyl chloride and others) first convert the hydroxy group of the oxime 1 into a good leaving group ... 

The preparation of a-iodocarboxylic acids is of particular interest, since iodide is a better leaving group as is chloride or bromide. A similar a-iodination with a phosphorus trihalide as catalyst is not known. However the iodination can be achieved in the presence of chlorosulfonic acid mechanistically the intermediate formation of a ketene 10 by dehydration of the carboxylic acid is assumed ... 

The oxygen atom at 21 is similarly an expendable group. Reaction of 241 (obtained from 185 by the usual procedure for introduction of the 9a-fluoro group) with methanesulfonyl chloride affords the 21 mesylate (242a). Replacement of the leaving group at 21 with iodine by means of potassium iodide in acetone followed by reduction of the halogen with zinc in acetic acid leads to fluorometholone (243). ... 

The net effect of nucleophilic acyl substitution is the replacement of the leaving group by the entering nucleophile. We ll see in Chapter 21, for instance, that acid chlorides are rapidly converted into esters by treatment with alkoxide ions (Figure 4). 

A nucleophilic acyl substitution reaction involves the substitution of a nucleophile for a leaving group in a carboxylic acid derivative. Identify the leaving group (Cl- in the case of an acid chloride) and the nucleophile (an alcohol in this case), and replace one by the other. The product is isopropyl benzoate. 

The reaction occurs by a nucleophilic acyl substitution pathway in which the carboxylic acid is first converted into a chlorosulfite intermediate, thereby replacing the -OH of the acid with a much better leaving group. The chloro-sulfitc then reacts with a nucleophilic chloride ion. You might recall from Section 17.6 Hint an analogous chlorosulfite is involved in reaction of an alcohol with SOCb to yield an alkyl chloride. 

Notice in both of the previous reactions that only "half" of the anhydride molecule is used the other half acts as the leaving group during the nucleophilic acyl substitution step and produces acetate ion as a by-product. Thus, anhydrides are inefficient to use, and acid chlorides are normally preferred for introducing acyl substituents other than acetyl groups. 

Conversion of Amides into Carboxylic Acids Hydrolysis Amides undergo hydrolysis to yield carboxylic acids plus ammonia or an amine on heating in either aqueous acid or aqueous base. The conditions required for amide hydrolysis are more severe than those required for the hydrolysis of add chlorides or esters but the mechanisms are similar. Acidic hydrolysis reaction occurs by nucleophilic addition of water to the protonated amide, followed by transfer of a proton from oxygen to nitrogen to make the nitrogen a better leaving group and subsequent elimination. The steps are reversible, with the equilibrium shifted toward product by protonation of NH3 in the final step. 

The Curtius rearrangement, like the Hofmann rearrangement, involve migration of an -R group from the G-O carbon atom to the neighboring nitro gen with simultaneous loss of a leaving group. The reaction takes place on heat ing an acyl azide that is itself prepared by nucleophilic acyl substitution of m acid chloride. 

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