22. Carboxylic Acid Derivatives: NAS

Determine the major product for the following reaction.

Determine the major product for the following reaction. 

Determine the major product for the following reaction. 

Determine the major product for the following reaction. 

Show how you would accomplish the following synthetic conversions efficiently and in good yield. You may use any necessary additional reagents and solvents.

(g) <IMAGE of reaction>

Show how you would use an acid chloride as an intermediate to synthesize.

(a) N-phenylbenzamide (PhCONHPh) from benzoic acid and aniline.

Show how you would convert the following starting materials to the indicated nitriles:

(a) phenylacetic acid --> phenylacetonitrile

Show how to synthesize the following compounds, using appropriate carboxylic acids and amines.

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Show how to synthesize the following compounds, using appropriate carboxylic acids and amines.

(b) <IMAGE>

Show how to synthesize the following compounds, using appropriate carboxylic acids and amines.

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(c) Propose a second mechanism for the reaction of benzoic acid with acetyl chloride to give acetic benzoic anhydride. This time, let the other oxygen of benzoic acid serve as the nucleophile to attack the carbonyl group of acetyl chloride. Because proton transfers are fast between these oxygen atoms, it is difficult to differentiate between these two mechanisms experimentally.

(e) Propose a mechanism for the reaction of aniline with ethyl acetate to give acetanilide. What is the leaving group in your proposed mechanism? Would this be a suitable leaving group for an SN2 reaction?

Show how you would synthesize the following esters from appropriate acyl chlorides and alcohols.

(e) tert-butyl acetate

(f) diallyl succinate

Show how you would use appropriate acyl chlorides and amines to synthesize the following amides.

(a) N,N-dimethylacetamide

(b) acetanilide (PhNHCOCH₃)

(a) Show how you would use acetic anhydride and an appropriate alcohol or amine to synthesize

(i) benzyl acetate (ii) N,N-diethylacetamide.

Show how you would accomplish the following syntheses. Some of these conversions may require more than one step.

(e) cyclohexylamine --> N-cyclohexylacetamide

(f) bromocyclohexane --> dicyclohexylmethanol

Predict the products of the following reactions.

(a) <IMAGE>

Predict the products of the following reactions.

(b) <IMAGE>

Predict the products of the following reactions.

(k) <IMAGE>

Predict the products of the following reactions.

(l) <IMAGE>

Show how you would accomplish the following syntheses in good yields.

(g) <IMAGE>

Propose a mechanism for the reaction of benzyl acetate with methylamine. Label the attacking nucleophile and the leaving group, and draw the transition state in which the leaving group leaves.

(a) Propose a mechanism for the acid-catalyzed reaction of salicylic acid with acetic anhydride. (b) Explain why a single drop of sulfuric acid dramatically increases the reaction rate.

Show how you would use anhydrides to synthesize the following compounds. In each case, explain why an anhydride might be preferable to an acid chloride.

(c) phthalic acid monoamide 

(d) succinic acid monomethyl ester

Predict the major products formed when benzoyl chloride (PhCOCl) reacts with the following reagents.

(d) anisole and aluminum chloride

(e) excess phenylmagnesium bromide, then dilute acid

(f) LiAlH(O-t-Bu)3

Predict the products of the following reactions.

(e) <IMAGE>

(f) <IMAGE>

One mole of acetyl chloride is added to a liter of triethylamine, resulting in a vigorous exothermic reaction. Once the reaction mixture has cooled, 1 mole of ethanol is added. Another vigorous exothermic reaction results. The mixture is analyzed and found to contain triethylamine, ethyl acetate, and triethylammonium chloride. Propose mechanisms for the

two exothermic reactions.

Phosgene is the acid chloride of carbonic acid. Although phosgene was used as a war gas in World War I, it is now used as a reagent for the synthesis of many useful products. Phosgene reacts like other acid chlorides, but it can react twice.

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(a) Predict the products formed when phosgene reacts with excess propan-2-ol.

Suggest the most appropriate reagent for each synthesis, and explain your choice.

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There are many methods for activating a carboxylic acid in preparation for coupling with an amine. The following method converts the acid to an N-hydroxysuccinimide (NHS) ester.

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(a) Explain why an NHS ester is much more reactive than a simple alkyl ester.

(c) Diethyl carbonate is a liquid reagent that is easy to handle. Also show how you might use diethyl carbonate instead of methyl isocyanate to make Sevin® insecticide.

Two widely used pain relievers are aspirin and acetaminophen. Show how you would synthesize these drugs from phenol.

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Suggest the most appropriate reagent for each synthesis, and explain your choice.

(d) <IMAGE>

Predict the products of the following reactions.

(d) anisole + succinic anhydride and aluminum chloride

Show how you would accomplish the following multistep syntheses. You may use any additional reagents and solvents you need.

(e) <IMAGE>

Write the mechanism for each of the following reactions:

a. the reaction of acetyl chloride with water to form acetic acid

Write the mechanism for the reaction of an amino acid with di-tert-butyl dicarbonate.

Predict the products of the following reactions.

(a) phenol + acetic anhydride

(b) phenol + acetic formic anhydride

(c) aniline + phthalic anhydride

Predict the products of the following reactions.

(i) <IMAGE>

(j) <IMAGE>

Predict the products of the following reactions:

(i) <IMAGE of reaction>

There are many methods for activating a carboxylic acid in preparation for coupling with an amine. The following method converts the acid to an N-hydroxysuccinimide (NHS) ester.

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(b) Propose a mechanism for the reaction shown.

There are many methods for activating a carboxylic acid in preparation for coupling with an amine. The following method converts the acid to an N-hydroxysuccinimide (NHS) ester.

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(c) Propose a mechanism for the reaction of the NHS ester with an amine, R-NH2.

Show how you would synthesize the following esters from appropriate acyl chlorides and alcohols.

(c) benzyl benzoate

(d) cyclopropyl cyclohexanecarboxylate

Show how the following ketones might be synthesized from the indicated acids, using any necessary reagents.

(a) propiophenone from propionic acid (using Friedel–Crafts acylation)

Predict the products of the following reactions:.

(h) <IMAGE>

Predict the products of the following reactions.

(i) <IMAGE>

Phosgene is the acid chloride of carbonic acid. Although phosgene was used as a war gas in World War I, it is now used as a reagent for the synthesis of many useful products. Phosgene reacts like other acid chlorides, but it can react twice.

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(b) Predict the products formed when phosgene reacts with 1 equivalent of methanol, followed by 1 equivalent of aniline.

Show how you would accomplish the following syntheses. Some of these conversions may require more than one step.

(a) isopentyl alcohol --> isopentyl acetate (banana oil)

Show how you would accomplish the following syntheses. Some of these conversions may require more than one step.

(b) 3-ethylpentanoic acid --> 3-ethylpentanenitrile

Show how you would accomplish the following syntheses. Some of these conversions may require more than one step.

(c) isobutylamine --> N-isobutylformamide

Show how you would accomplish the following syntheses. Some of these conversions may require more than one step.

(d) ethyl acetate --> 3-methylpentan-3-ol