Carbonyl derivatives, dehydration

A recent procedure which utilizes the pivaloyl derivative of o-bromoaniline as one of the fragments is also a type llac approach. The compound is converted to its dilithio derivative at -78 °C. Reaction with a-halo ketones then affords indole hydrates by N-alkylation and reaction of the o-lithiated position with the carbonyl group dehydration subsequently yields indoles (equation 108) (81TL1475). The (V-trifluoroacetyl and N-t-butoxycarbonyl derivatives of o-bromoaniline exhibit similar reactivity. 

The aldol condensation is the reaction of an aldehyde or ketone enolate with an aldehyde or ketone to give a /3-hydroxy aldehyde or ketone. A simple aldol reaction is one in which the enolate nucleophile is derived from the carbonyl electrophile. Very often the /3-hydroxy carbonyl product dehydrates to give an... 

Reactions of phenylthiocyclopropyl lithium with alkyl halides and epoxides have also been reported to deliver products opened to a variety of carbonyl derivatives jS-(l-Phenylthio)cyclopropyl enones have been prepared by using lithium salts of a-hydroxymethylene ketones as electrophiles and dehydrating with acid (equation 110). Rearrangement to cyclobutanones occurs with trifluoroacetic acid, whereas thermal vinylcyclopropane-cyclopentene expansion sometimes gives mixtures of regioisomers . 

As can be seen from equations 2-5, the formation of A -acylenamines proceeds from derivatives of carboxylic acids (having an oxidation level equal to three ), namely anhydrides or add halides RCOX or amides RCONH2, on the one hand, and from carbonyl compounds or their derivatives (oxidation level equal to two ), namely enamines 3, acetylenes 5, or vinyl ethers 6, on the other. Indeed, the acetylenes 5, being the dehydration products of enols, may be regarded as having a masked carbonyl functionwhile the enamines 3 rank with vinyl ethers, vinyl esters and enols, as the heteroanalogs of these carbonyl derivatives (see Section IV). 

The products are known as benzimidazoles. The reactants are ortho-phenylenediamine derivatives and aliphatic adds in a refluxing HCl solution. The reaction is shown in a reasonable mechanistic form in Scheme 4.24. Here, it is proposed that an amino group displaces OH from the acid to form an amide (4.25), which is a known process. Amide carbonyls do not generally behave in the way aldehyde and ketone carbonyls do, but nevertheless it has been suggested that the second amino group does add to the amide carbonyl, with dehydration of the adduct, to form the double bond in the imidazole ring (4.26). 

Monodithiocarbamates can be prepared from phenylene diamines in the presence of a second, more basic amine. For example, addition of carbon disulfide and NEta to 1,2-diaminobenzene affords the yellow triethylammonium dithiocarbamate salt in high yield (115). The latter can then be reacted with various a-halogenated carbonyl derivatives resulting in cyclization and dehydration to give the new amines. These in turn react with carbon disulfide and... 

Amides can, in principle, be prepared by thermal dehydration of ammonium salts of carboxylic acids, such as [NH4] [RCOO] or [RNH3]+[RCOO], but this route is rarely used in practice, because of the reversibility of the process. Most strategies depend on the reaction of amines with carbonyl derivatives where there is a better leaving group than OH attached to the carbonyl. 

Borohydrides reduce a-substituted ketones to the corresponding a-substituted alcohols, and such products can be further reduced to olefins (see section VIII). Other reagents serve, through participation of the carbonyl group, to remove the substituent while leaving the ketone intact. The zinc or chromous ion reduction of a-halo ketones is an example of this second type, which is not normally useful for double bond introduction. However, when the derivative being reduced is an a,jS-epoxy ketone, the primary product is a -hydroxy ketone which readily dehydrates to the a,jS-unsaturated ketone. Since... 

Condensation of an appropriately substituted phenylacetic acid with phthalic anhydride in the presence of sodium acetate leads to aldol-like reaction of the methylene group on the acid with the carbonyl on the anhydride. Dehydration followed by decarboxylation of the intermediate affords the methylenephthal-ides (12). Treatment of the phthalides with base affords directly the indandiones, probably via an intermediate formally derived from the keto-acid anion (13). The first agent of this class to be introduced was phenindandione (14) this was followed by anisindandione (1S) and chlorindandione (16). ... 

Nitro compounds are versatile precursors for diverse functionalities. Their conversion into carbonyl compounds by the Nef reaction and into amines by reduction are the most widely used processes in organic synthesis using nitro compounds. In addition, dehydration of primary nitro compounds leads to nitrile oxides, a class of reactive 1,3-dipolar reagents. Nitro compounds are also good precursors for various nitrogen derivatives such as nitriles, oximes, hydroxylamines, and imines. These transformations of nitro compounds are well established and are used routinely in organic synthesis. 

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