A-halo

This reaction involves the condensation of an aldehyde or ketone with an a-halo ester in the presence of a basic condensing agent (sodium ethoxlde, sodamide, finely divided sodium or potassium iert.-butoxide) to give a glycldio (or ap-epoxy) ester. Thus acetophenone and ethyl chloroacetate yield phenyl-methylglycidic ester (I) ... 

Acid chlorides and bromides, allyl halides, a-halo-ketones, esters, amides and nitriles react at 25° within 3 minutes. Vinyl and aryl halides are inert. 

Synthesis Since a-halo-carbonyl compounds are very reactive electrophiles, we can use a short cut ... 

We need for B a derivative of a ketone in which the normal polarity is inverted, and you will realise from frames 158-161 that the a-halo carbonyl compoimd is ideal. So how would you make TM 171 ... 

Analysis Either way round will do, so let s arbitrarily chose ketone and a-halo ester ... 

Synthesis Our problems are not yet oyer because if we combine ketone and a-halo ester in base, quite a different reaction occurs. Can you draw a mechanism for it ... 

Alkyl Halides, Polyhalides, a-Halo Ketones and Esters... 

Substitutive nomenclature of alkyl halides treats the halogen as a halo—(fluoro chloro bromo or lodo ) substituent on an alkane chain The carbon chain is numbered m the direction that gives the substituted carbon the lower number... 

Aldehyde or ketone Halogen a Halo aldehyde or ketone Hydrogen halide... 

Once formed this enol reacts rapidly with the halogen to form an a halo ketone OH O... 

The cationic intermediate is simply the protonated form (conjugate acid) of the a halo ketone Deprotonation of the cationic intermediate gives the products... 

This reaction is of synthetic value in that a halo acids are reactive sub strates m nucleophilic substitution reactions... 

Analyzing the target molecule in this way reveals that the required alkyl halide IS an a halo ketone Thus a suitable starting material would be bromomethyl phenyl ketone... 

Nucleophilic substitution by ammonia on a halo acids (Section 19 16) The a halo acids obtained by halogenation of car boxylic acids under conditions of the Hell-Volhard-Zelinsky reaction are reac tive substrates in nucleophilic substitu tion processes A standard method for the preparation of a ammo acids is dis placement of halide from a halo acids by nucleophilic substitution using excess aqueous ammonia... 

Among compounds other than simple alkyl halides a halo ketones and a halo esters have been employed as substrates m the Gabriel synthesis Alkyl p toluenesul fonate esters have also been used Because phthalimide can undergo only a single alkyl ation the formation of secondary and tertiary amines does not occur and the Gabriel synthesis is a valuable procedure for the laboratory preparation of primary amines... 

One of the oldest methods for the synthesis of ammo acids dates back to the nineteenth century and is simply a nucleophilic substitution m which ammonia reacts with an a halo carboxylic acid... 

The a halo acid is normally prepared by the Hell-Volhard-Zehnsky reaction (see Sec tion 19 16)... 

Preparation. The general preparation of y acids is by the hydrolysis of an a-halo acid or by the acid hydrolysis of the cyanohydrins of an aldehyde or a ketone. 

Substitution Reactions. Reaction with nitrous acid in dilute aqueous solutions yields the corresponding hydroxy acid or in solution containing a hydrohahc acid, the corresponding a-halo acid, with inversion in many cases. 

They are generally produced in neutral to slightly acid solution. A/-Halo-A/-sodioamidates, A/-halo-A[-sodiocarbamadiates, and... 

Amino Acids. The formation of A/-halo-a-amino acids involves halogenation of the acid anion (13). /V-Cb1oro-CX-amino acids decompose to aldehydes and nitriles, the selectivity depending on pH and stoichiometry (110). For example, AJ-chloroalanine decomposes in the 6.5—10 pH range. 

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