Halogenation of amides

The classical synthesis of imidoyl chlorides involves the reaction of N-substituted carboxylic acid amides with phosphorus pentahalides. Wallach and his students (288-292 1876-1882 investigated this reaction 

In contrast, unsubstituted amides react with phosphorus pentachloride in a different manner, yielding the corresponding trichlorophosphazenes (VII). The correct structural assignment of the obtained products was performed by Kirsanov in 1955 The trichlorophosphazenes eliminate 

In the reaction of N-substituted carboxylic acid amides with phosphorus pentachloride generally the corresponding free imidoyl chlorides (I) or their hydrochlorides (II) (iminium chlorides) are formed. If the iminium chlorides are obtained initially, dehydrochlorination can be achieved by simply heating or using a stronger base, such as triethylamine, as the hydrogen chloride scavenger. 

In the reaction of aliphatic carboxylic acid amides having hydrogens adjacent to the C=N bond, self-condensation of the generated imidoyl 

If an ortho-substituted benzene ring is attached to the nitrogen, the self-condensation is minimized due to steric hindrance and the yield of imidoyl chlorides increases in this order CH3 Cl Br ( ). Likewise, lowering of the basicity of the nitrogen prevents condensation. For example, N-sulfonimidoyl chlorides of aliphatic carboxylic acids are obtained in excellent yield ( ). The carboxylic acid amides of a,j8-unsaturated acids also do not undergo tautomerization, because the formation of allenes is not favored under mild conditions 

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The O-S exchange method in presence of a-halogenated carbonyl compound is a very good one for thiazole compounds. The thioamide is prepared in situ by the action of amide upon phosphorus pentasulphide with solvent. The a-halogenated aldehyde reacts directly. But the O-Se exchange cannot be performed with a-halogenated carbonyl compounds because of the apparition of phosphoric acid. (Scheme 3), The C-Se bond is very sensitive to add pH. 

Ketone formation can also be avoided if one of the functional acyl halogens ia phosgene is blocked. Carbamyl chlorides, readily obtained by the reaction of phosgene with ammonia or amines, are suitable reagents for the preparation of amides ia direct Friedel-Crafts acylation of aromatics. The resulting amides can be hydroly2ed to the corresponding acids (134) ... 

A/-Chloro fatty acid amides have been synthesized from the direct halogenation of the amide in boiling water (28). They are useful as reactive intermediates for further synthesis. Fluorination has also been reported by treating the fatty amide with fluorine-containing acid reagents at 200 °C to reach a fluorinated amide with less reactivity toward fluorocarbon polymers (29). 

Violent interaction of amides and analogues with halogens, halogen derivatives and acid chlorides... 

Nitronate(47a) is not the only oxazete derivative. For example, sterically hindered nitroalkenes (42b-d) can be prepared by nitration and halogenation of readily available allenes (48). Compounds (42b-d) are rather smoothly isomerized into the corresponding four-membered cyclic nitronates (47b-d) by the first-order reaction equation (168). Storage of nitronate (47c) is accompanied by its slow transformation into acid chloride (47e) from which amide (47f) can be easily synthesized. 

In these reaetions, the most reliable mechanism is considered to involve the initial metal-coordination at the nitrogen atom of the pyridine ring and the subsequent attack of an alkyl or aryl anion at the most probable cationic sites on the ring, namely, the 2- and/or 4-position of the ring. If a 2-halogen substituted pyridine is used, the nucleophilic anion attacks the 6-position. Thus, the addition is a more prefered reaction than the ipso-substitution as shown in reaction (29). The substitution of amide or phenyl-... 

Nitrosation of, 401 Ortho acids, 41-42 Ortho amides, 42 Orthocarbonates, 42 Ortho esters, 41-68 halogenation of acyl groups, 58-60 monocyclic, 51-53 polycyclic, 51... 

A number of other methods exist for the a halogenation of carboxylic acids or their derivatives.134 The acids or their chlorides or anhydrides can be a chlorinated by treatment with CuCl in polar inert solvents (e.g., sulfolane).135 Acyl halides can be a brominated or chlorinated by use of N-bromo- or N-chlorosuccinimide and HBr or HC1.136 The latter is an ionic, not a free-radical halogenation (see 4-2). Direct iodination of carboxylic acids has been achieved with L-Cu(II) acetate in HO Ac.137 Acyl chlorides can be a iodinated with L and a trace of HI.138 Carboxylic esters can be a halogenated by conversion to their enolate ions with lithium N-isopropylcyclohexylamide in THF and treatment of this solution at - 78° with I2138 or with a carbon tetrahalide.139 Carboxylic acids, esters, and amides have been a fluorinated at -78°C with F2 diluted in Ni.,4°... 

Halogenation of Aromatic and Heterocyclic Compounds by Means of N-Halogenated Amides N. P. Buu-Hoi, Rec. Chem. Prog., 1952,13, 30-36. 

Halogenation of trans-2-pyridone photodimers results in [l,3]-migration of an amide nitrogen (Scheme 29).52... 

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