L-24 Acid Chloride

Ghada Acid chloride & Acid anhydride By the end of this lecture the Specific student is expected to: • Define general concept of Objectives hydrocarbons derivatives. • Compare up between deferent types L-23 of functional groups. • Describe the structure of Acid Acid derivatives. chloride and Acid anhydride, And acid • Nomenclature the Acid chloride and anhydride Acid anhydride • Draw the structure of Acid chloride Phys./chem. and Acid anhydride Discuss the properties physical and chemical • Properties of Acid chloride and Acid anhydride Definition The functional group of an acid chloride, also known as acyl chloride, is an acyl group bonded to a chlorine atom. The simplest member of this family is acetyl chloride (CH3COCl), where the acyl group is bonded to a chlorine atom. Nomenclature

Acid chlorides are named by replacing the ic acid ending with -yl choride or replacing the carboxylic acid ending with -carbonyl chloride. Acid chlorides and acid anhydrides • Acid chlorides are named as follows: – first as a carboxylic acid – Remove the “-ic acid” and add “-oyl chloride”

Propanoyl chloride 3-Methylbutanoyl chloride Examples Physical properties • Lacking the ability to form hydrogen bonds, acid chlorides have lower boiling and melting points than similar carboxylic acids. For example, acetic acid boils at 118 °C, whereas acetyl chloride boils at 51 °C. • The simplest acyl chloride is ethanoyl chloride or acetyl chloride; methanoyl chloride is not stable Chemical properties Preparation of acid chloride Acid chlorides are prepared from the corresponding carboxylic acids, most commonly from the reaction with thionyl chloride or oxalyl chloride Chemical properties Reactions of acid chloride

Acid chlorides are the most reactive carboxylic acid derivatives, and easily converted to acid anhydrides, esters and amides via nucleophilic acyl substitutions . Acid chlorides are sufficiently reactive with H2O, and quite readily hydrolysed to carboxylic acid. Reactions of acid chloride Acid chlorides are easily converted to 1˚ alcohols and aldehydes and 3 ˚ alcohols and ketones through the choice of appropriate metal hydride and organometallic reagents. Acid chloride reacts with benzene in the presence of Lewis acid (AlCl3) in Friedel–Crafts acylation. Reactions of acid chloride

Hydrolysis reaction:

+ H2O + HCl

Esterification:

+ HCl Reaction with H2O - Acid Chlorides

– Low-molecular-weight acid chlorides react rapidly with water. – Higher molecular-weight acid chlorides are less soluble in water and react less readily.

O O CH3CCl + H2O CH3COH + HCl Acetyl chloride Reaction with Alcohols • Acid halides react with alcohols to give esters. – Acid halides are so reactive toward even weak nucleophiles such as alcohols that no catalyst is necessary. – If the alcohol or resulting ester is sensitive to HCl, the reaction is carried out in the presence of a 3° amine to neutralize the acid. O O

Cl + HO O + HCl Butanoyl Cyclohexanol Cyclohexyl butanoate chloride Reaction with Ammonia

• Acid halides react with ammonia, 1° amines, and 2° amines to form amides. – Two moles of the amine are required per mole of acid chloride.

O O + - Cl + 2NH3 NH2 + NH4 Cl Hexanoyl Ammonia Hexanamide Ammonium chloride chloride Acid Chlorides with Salts

• Acid chlorides react with salts of carboxylic acids to give anhydrides. – Most commonly used are sodium or potassium salts.

O O O O + + - + - CH3 CCl Na OC CH3 COC + Na Cl Acetyl Sodium Acetic benzoic chloride benzoate anhydride Gilman Reagents

• Acid chlorides at -78°C react with Gilman reagents to give ketones. – Under these conditions, the TCAI is stable, and it is not until acid hydrolysis that the ketone is liberated.

O O 1 . ( CH3 ) 2 CuLi, ether, -78°C Cl 2 . H2 O Pentanoyl chloride 2-Hexanone Gilman Reagents

– Gilman reagents react only with acid chlorides. – They do not react with acid anhydrides, esters, amides or nitriles under the conditions described.

O 1 . ( CH ) CuLi, ether, -78°C H CO 3 2 3 Cl 2 . H2 O O O

H 3CO O Uses of Acid Chloride

• Acetyl chloride is used in organic synthesis as an acetylating agent and in testing for water and/ or cholesterol in organic liquids, in the pharmaceutical industry and in pesticide manufacture. Acid Anhydride Definition

The functional group of an acid anhydride is two acyl groups bonded to an oxygen atom. These compounds are called acid anhydrides or acyl anhydrides, because they are condensed from two molecules of carboxylic acid by the loss of a water molecule. Definition An acid anhydride may be symmetrical, where two acyl groups are identical, or it may be mixed, where two different acyl groups are bonded to an oxygen atom. The simplest member of this family is acetic anhydride, (CH3CO)2O, where the acyl group (CH3CO) is bonded to an acetate group (CH3CO2). Acid Anhydride Examples Nomenclature of acid anhydrides

Symmetrical acid anhydrides are named by replacing the -acid suffix of the parent carboxylic acids with the word anhydride. Mixed anhydrides that consist of two different acid-derived parts are named using the names of the two individual acids with an alphabetical order. Nomenclature of acid anhydrides Acid Anhydrides

• Cyclic anhydrides are named from the dicarboxylic acids from which they are derived.

O O O

O O O

O O O Succinic Maleic Phthalic anhydride anhydride anhydride Acid Anhydrides O O O O C C O CH3 O butanoic anhydride acetic benzoic anhydride butyric anhydride

O OH O O O HO O succinnic acid succinnic anhydride Physical properties • Solubility in water Acid anhydride can't be said to dissolve in water because it reacts with it to give carboxyloc acid. There is no such thing as an aqueous solution of acid anhydride. Physical properties • Boiling point Ethanoic anhydride( as example) boils at 140°C. This is because it is a fairly big polar molecule and so has both van der Waals dispersion forces and dipole-dipole attractions. It does not, however, form hydrogen bonds. That means that its boiling point isn't as high as a carboxylic acid of similar size. For example, pentanoic acid (the most similarly sized acid) boils at 186°C. Chemical properties Preparation of acid anhydride Anhydrides are produced most commonly by the reaction of an acid chloride and a carboxylic acid or carboxylate salt. Five- or six- membered cyclic anhydrides are prepared by heating dicarboxylic acids at high temperatures. Chemical properties Reactions of acid anhydride

Acid anhydrides are the second most reactive of the carboxylic acid derivatives. They are fairly readily converted to the other less reactiv carboxylic acid derivatives, e.g. esters, carboxylic acids and amides. Acid anhydrides undergo many reactions similar to those of acid chlorides, andthey can often be used interchangeably. Reactions of acid anhydride Reaction with H2O - Anhydrides

– Low-molecular-weight anhydrides react readily with water to give two molecules of carboxylic acid. – Higher-molecular-weight anhydrides also react with water, but less readily.

O O O O CH3COCCH3 + H2O CH3COH + HOCCH3 Acetic anhydride Reaction with Alcohols • Acid anhydrides react with alcohols to give one mole of ester and one mole of a carboxylic acid.

O O O O + CH3 COCCH3 + HOCH2 CH3 CH3 COCH2 CH3 CH3 COH Acetic anhydride Ethanol Ethyl acetate Acetic acid

– Cyclic anhydrides react with alcohols to give one ester group and one carboxyl group. O O O + O HO OH O O Phthalic 2-Butanol anhydride (sec-Butyl alcohol) (sec-Butyl hydrogen phthalate Reaction with Ammonia

• Acid anhydrides react with ammonia, and 1° and 2° amines to form amides. – Two moles of ammonia or amine are required.

O O O O - + + + CH3 COCCH3 2NH3 CH3 CNH2 CH3 CO NH4 Acetic Ammonia Acetamide Ammonium anhydride acetate Acid chlorides and acid anhydrides

• Acid chlorides and anhydrides have structures that are quite similar to carboxylic acids and esters. • Both are able to be hydrolized to produce carbolxylic acids.

carboxylic acid ester acid chloride acid anhydride • Acid chlorides are produced by reaction of a carboxylic acid

with an inorganic chloride (PCl3, PCl5, or SOCl2).

inorganic chloride Acid chlorides and acid anhydrides

• Acid anhydrides are made by condensation reactions between carboxylic acids (or between acid chlorides and carboxylic acids):

Propanoic acid Propanoic acid Propanoic anhydride • Naming is straightforward: indicate the names of the acids used to make the anhydride (without the “acid” part included)

Ethanoic propanoic anhydride Acid chlorides and acid anhydrides Acyl transfer reactions

• Carboxylic acids (esters, acid chlorides…) possess an acyl group (notice how this is different that the carboxyl group of the acid)

Acyl group

• Acyl transfer reactions occur during protein synthesis. The reaction involves the formation of a new bond between the acyl group and another molecular fragment. • One example of an acyl transfer occurs during an esterification:

H2O

carboxylic acid alcohol ester Reactivity of Acid Derivatives Uses of Acid anhydride

• The largest volume use for acetic anhydride is as a raw material for cellulose acetate fibers and plastics. It is widely used as an acetylating agent or in chemical synthesis. Acetic anhydride is also a key raw material for aspirin, acetaminophen and other pharmaceuticals manufacturing