Acid chloride reaction with ammonia

Reaction requires two moles of ammonia or amine, one to form the amide and one to neutralize the carboxylic acid by-product. The mechanism is analogous to that of the acid chloride reaction with ammonia or amines. 

One of the first compounds to be introduced to the clinic, aztreonam (40-9), has been produced by total synthesis. Constmction of the chiral azetidone starts with amide formation of L-threonine (40-1) via its acid chloride treatment with ammonia leads to the corresponding amide (40-2). The primary amino group in that product is then protected as its carbobenzyloxy derivative (40-3). Reaction of that product with methanesulfonyl chloride affords the mesylate (40-4). Treatment of that intermediate with the pyridine sulfur trioxide complex leads to the formation of the A -sulfonated amide (40-5). Potassium bicarbonate is sufficiently basic to ionize the very acidic proton on the amide the resulting anion then displaces the adjacent mesylate to form the desired azetidone the product is isolated as its tetrabutyl ammonium salt (40-6). Catalytic hydrogenation over palladium removes the carbobenzyloxy protecting group to afford the free primary amine (40-7). The... 

The next preparation will deal with this reaction. The acid-chlorides react with ammonia as well as with primary and secondary organic bases with great ease ... 

ANTIMONY TRICHLORIDE (10025-91-9) Cl3Sb Contact with moist air forms corrosive hydrogen chloride fumes. Contact with water, steam forms hydrochloric acid and toxic antimony oxychloride. Aqueous solution is an acid. Violent reaction with ammonia, strong bases, amines, amides, and inorganic hydroxides alkali metals finely divided aluminum potassium, sodium. Attacks metals, releasing flammable... 

MESYL CHLORIDE (124-63-0) Combustible liquid (flash point >212°F/>100°C). Reacts with water, acid, or acid fumes, forming hydrochloric acid. Violent reaction with ammonia, caustics, strong oxidizers. Aqueous solution incompatible with sulfuric acid, ammonia, aliphatic amines, alkanolamines, bases, isocyanates, alkylene oxides, epiehlorohy-drin. Attacks metals in the presence of moisture. 

When the -OH of a carboxylic acid is replaced by an -NH2, the compound produced is an amide. Amides are neutral to mildly basic compounds. They can be made from acids, acid chlorides, acid anhydrides, and esters by reaction with ammonia or primary and secondary amines. The amide linkage is found in polyamide resins such as nylon. 

The presence of three nitro groups on the aromatic ring of picryl chloride makes the chloro group extremely reactive towards nucleophiles. Picryl chloride (87) is hydrolyzed to picric acid (4) in the presence of hot water or aqueous sodium hydroxide. Aminolysis of picryl chloride in the presence of primary and secondary amines is complete in minutes at room temperature. Picryl chloride is therefore a very useful starting material for the synthesis of a range of other picryl derivatives. The reaction of picryl chloride (87) with ammonia can be used to synthesize 2,4,6-trinitroaniline (53) (picramide). Treatment of picryl chloride with alcohols under reflux forms picric acid and the alkyl chloride of the corresponding alcohol, whereas the same reaction in the presence of alkali metal hydroxides, or the alkoxide anion of... 

Ethylene adds hypochlorous acid more readily than it adds either moist chlorine or hydrogen chloride. Bubbled into chlorine water, it is converted completely into ethylene chlorohydrin, and by the hydrolysis of this substance glycol is obtained. Ethylene chlorohydrin is important also because of its reaction with ammonia whereby mono-, di-, and triethanolamine are formed, substances which are used in the arts and are not without interest for the explosives chemist. Ethylene may be oxidized catalytically in the gas phase to ethylene oxide which reacts with water to form glycol and with glycol to form diglycol which also is of interest to the dynamite maker. 

The acid filtrate is treated with excess of ammonium chloride and with ammonia to precipitate the ferric oxide and any alumina, the precipitate being tested for the latter in the usual way. The filtrate is divided into three parts one is acidified with acetic acid and tested for copper with ferrocyanide in another the manganese (if present) is precipitated with ammonium sulphide, lime and magnesia being then tested for in the third sulphates are tested for with barium chloride. Manganese is best sought in a separate portion of the substance by the well-known dry reaction. 

Thiadiazine 199 is formed from the reaction between either sulfur dichloride and dichloromalononitrile or N,2,2-trichlorocyanoacetimidoyl chloride and sulfur (Scheme 15). Product 199 is very unstable, but treatment with formic acid transforms it into 200 (Scheme 15). The chlorine atoms of 200 can be successively replaced by reaction with ammonia, primary or secondary amines, alkoxide, and other nucleophiles (73TL4489). 

A reaction of rather less general application, but one which produces valuable intermediates, is the treatment of dithiosalicylamide and its A-substituted derivatives with phosphorus pentachloride. Thus, A.A-diethyldithiosalicylamide (20) yields 3-chloro-2-ethyl-l,2-benz-isothiazolium chloride (21).14-16 This salt (21) is a versatile compound for example, heating it with diethylamine gives 3-diethylamino-l,2-benzisothiazole (22)16, treatment with base yields 2-ethyl-l,2-benzisothiazolinone (23), and reaction with ammonia, followed by hydrochloric acid, affords 3-ethylamino-l,2-benzisothiazole (24).14 This final reaction involves an interesting rearrangement which will be discussed in more detail in Sections II, C, 2 and II, C, 3. 

Using the principles we ve outlined above, you should be able to see how these compounds can be interconverted by substitution reactions with appropriate nucleophiles. We ve seen that acid chlorides react with carboxylic acids to give acid anhydrides, and with alcohols to give esters. They ll also react with amines (such as ammonia) to give amides. 

Direct methods for making the complex starting with cobalt(II) chloride involve preparation of a carbonatotetra-ammine salt by air oxidation and subsequent reaction with ammonia and hydrochloric acid. The procedure is time-consuming but gives excellent yields. A more rapid and simpler synthesis, which utihzes the reaction of hydrogen... 

Thionyl chloride is frequently the reagent of choice for the dehydration of higher-molecular-weight amides, since the secondary products are gaseous and the nitrile is more readily purified. Oftentimes, the higher fatty acids are converted to the nitriles in a single operation via the intermediate ammonium salts and amides. For this purpose, dry ammonia gas is passed into the molten acids at 290-300° the yields of nitriles are excellent (80-85%). A small amount of 85% phosphoric acid appreciably reduces the reaction time. Another procedure consists in passing the acid vapors mixed with ammonia over silica gel at 500°. This technique... 

In the laboratory, amides and esters are usually prepared from the acid chloride rather than from the acid itself. Both the preparation of the acid chloride and its reactions with ammonia or an alcohol are rapid, essentially irreversible reactions. It is more convenient to carry out these two steps than the single slow, reversible reaction with the acid. For example n... 

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