Amide chlorides chlorination

Several min after addition of ethanol to a mixture of the amide chloride ( fusible white precipitate ) and iodine, an explosion occurs. Addition of the compound to chlorine gas or bromine vapour leads to a delayed violent or explosive reaction. Amminemetal salts behave similarly, and formation of A-halogen compounds is involved in all cases. 

Wallach was the first (1874) to report on the transformation of carboxylic acid amides to amide chlorides by treatment with PCls " various types of amides were converted by this reagent to chloromethyleneiminium chlorides (30 equation 5j(jg reactions can include the a-chlorination of... 

A very efficient preparation of amide chlorides comprises the action of elemental chlorine on thioamides in CH2CI2 or CCU even amide chlorides which possess electron-attracting substituents in the a-position have been prepared in this... 

The formation of amide chlorides from nitriles and hydrogen halides under anhydrous conditions is a well-known reaction of wide scope7- There has been some confusion on the nature of the reaction products, but it has turned out that the isolable species are amide chlorides. The thermal stability of the addition products strongly depends on the acidity of the hydrogen halide used. Iodides are more stable than bromides, which in turn are more stable than the chlorides. As a consequence, thermally stable HQ adducts (38 equation 22) can be prepared if Lewis acids ate present, which incorporate the chlorine anion to give a less basic anion (39). 

Amide chlorides which contain an a-CH or a-CH2 group readily undergo chlorination in these positions. The amide chlorides thus formed were not isolated but their hydrolysis products, a-chlorinated amides (53) and (54 Scheme 2) were formed. 444... 

S-alkylation to thioamidium salts and chlorination to amide chlorides (ref. 8, Scheme 8). The thioamidium salts react with hydride or other nucleophiles to give many useful intermediates. 

Compound 12 cyclizes with hydrazine to give a pyrazoline which can be dehydrogenated to afford pyrazole 12. Many trifluoromethylated pyrazoles are known as described in an excellent review (ref. 27). Alcohols U can be methylated using NaH/TfOMe. These methyl ethers could not be hydrolyzed to the corresponding Mosher acid. As the hydroxyl is now protected by an alkyl group, the thioamide moiety can be chlorinated to give the amide chloride 14- This unstable compound was directly cyclized with benzothiazole (Scheme 35). 

MERCURY AMIDE CHLORIDE (10124-48-8) Reacts violently with halogens barium, chlorine, fluorine, and metal salts of amines. Contact with acids or acid fumes causes decomposition, producing hydrogen chloride fumes. Incompatible with organic anhydrides, acrylates, alcohols, aldehydes, alkylene oxides, substituted allyls, cresols, caprolactam solution, epichlorohydrin, ethylene dichloride, glycols, isocyanates, ketones, maleic anhydride, nitrates, nitromethane, phenols, vinyl acetate. May corrode aluminum, copper, zinc, and some stainless steel in the presence of moisture. 

Wallach was the first (1874) to report on the transformation of carboxylic acid amides to amide chlorides by treatment with PCls various types of amides were converted by this reagent to chloromethyleneiminium chlorides (30 equation lg). - > Side reactions can include the a-chlorination of the amide chloride. If excess PCIs is used, the formation of iminium salts with complex ions (31) has been reported. The very labile bromomethyleneiminium bromides (32 equation 19) can be obtained by action of PBrs on tertiary amides. The iodomethyleneiminium salt (33) was prepared from DMF and diphosphorus tetraiodide in CS . ... 

Nitrogen is a better electron parr donor than oxygen and amides have a more stabilized carbonyl group than esters and anhydrides Chlorine is the poorest electron pair donor and acyl chlorides have the least stabi lized carbonyl group and are the most reactive... 

Benzyl chloride is manufactured by the thermal or photochemical chlorination of toluene at 65—100°C (37). At lower temperatures the amount of ring-chlorinated by-products is increased. The chlorination is usually carried to no more than about 50% toluene conversion in order to minimize the amount of benzal chloride formed. Overall yield based on toluene is more than 90%. Various materials, including phosphoms pentachloride, have been reported to catalyze the side-chain chlorination. These compounds and others such as amides also reduce ring chlorination by complexing metallic impurities (38). 

An interesting alternate synthesis for this agent starts with the chlorination of the benzylic carbon of 8 by means of N ( li lorosuccinimide. Treatment of the chloro compound (9) with M)Jium amide in liquid ammonia serves to remove remaining proton I ll that carbon. This carbanion (10) then performs an alkylation iiMCtlon on unreacted starting chloride. The product of this iilkylation (11) still contains a fairly acidic benzylic proton ... 

Diuretic activity can be retained in the face of replacement of one of the sulfonamide groups by a carboxylic acid or amide. Reaction of the dichlorobenzoic acid, 174, with chlorsulfonic acid gives the sulfonyl chloride, 175 this is then converted to the amide (176). Reaction of that compound with furfuryl ine leads to nucleophilic aromatic displacement of the highly activated chlorine at the 2 position. There is thus obtained the very potent diuretic furosemide (177). ... 

Replacement of chlorine on the pendant benzoyl group by azide is apparently consistent with antiinflammatory activity. Acylation of indomethacin intermediate with p-nitrobenzoyl chloride leads to the corresponding amide (7). Saponification ( ) followed by reduction of the nitro group gives the amine 9. The diazonium salt (10) obtained on treatment with nitrous acid is then reacted with sodium azide there is thus obtained zidomethacin (11). 

Electronically, we find that strongly polarized acyl compounds react more readily than less polar ones. Thus, acid chlorides are the most reactive because the electronegative chlorine atom withdraws electrons from the carbonyl carbon, whereas amides are the least reactive. Although subtle, electrostatic potential maps of various carboxylic add derivatives indicate the differences by the relative blueness on the C-O carbons. Acyl phosphates are hard to place on this scale because they are not used in the laboratory, but in biological systems they appear to be somewhat more reactive than thioesters. 

Allylmagnesium bromide, 41, 49 reaction with acrolein, 41, 49 5-Allyl-l,2,3,4,5-pentachlorocyclopen-tadiene, 43, 92 Allyltriphenyltin, 41, 31 reaction with phenyllithium, 41, 30 Aluminum chloride, as catalyst, for isomerization, 42, 9 for nuclear bromination and chlorination of aromatic aldehydes and ketones, 40, 9 as Friedel-Crafts catalyst, 41, 1 Amidation, of aniline with maleic anhydride, 41, 93... 

Interaction of the two compounds led to the evolution of a toxic gas thought to be chlorine [1], It is the far more poisonous phosgene, arising from the known base-catalysed disproportionation of the carbonate to oxalyl chloride and phosgene, which occurs even at ambient temperature [2], (The editor knows that amides, too, catalyse this rearrangement and suspects that Lewis acids will also)... 

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