A -alkylated

ON A alkylating agents, intercalating agents, wrong substrates (Trofan horses, e.g, S-fluorouracil)... 

It is of interest to note that by substituting alkyl bromides for cyciohexyl bromide the corresponding a-phenyl-a-alkyl-acetonitriles are obtained, which may be hydrolysed to the a-phenylaliphatic acids thus with ethyl iodide a-phenyl-lwt3Tonitrile is produced, hydrolysed by ethanoUo potassium hydroxide to a-phenylbutyric acid. 

The (E)-a-alkyl-/5-silylacrylate 22 is prepared by regio- and stereoselective car-bony lation of the trimethylsilylalkyne 21 using a Pd catalyst coordinated by SnClj and dppf[20]. 

Alkylation can also be accomplished with electrophilic alkenes. There is a dichotomy between basic and acidic conditions. Under basic conditions, where the indole anion is the reactive nucleophile, A-alkylation occurs. Under acidic conditions C-alkylation is observed. The reaction of indole with 4-vinylpyri-dine is an interesting illustration. Good yields of the 3-alkylation product are obtained in refluxing acetic acid[18] whereas if the reaction is done in ethanol containing sodium ethoxide 1-alkylation occurs[19]. Table 11.2 gives some examples of 3-alkylation using electrophilic alkenes. 

Thiazole acetic acids and their hotnologs can also be prepared by cyclization procedures 4-thiazole alkanoic acids and their salts were prepared by treating a thioamide with a -y-chloro- or 7-bromoacetoacetic or their a-alkyl derivatives (4, 10, 16, 22, 273, 275, 281, 640, 647, 695). 

Because etiolate anions are sources of nucleophilic carbon one potential use m organic syn thesis IS their reaction with alkyl halides to give a alkyl denvahves of aldehydes and ketones... 

Section 21 9 Michael addition of the enolate ions derived from ethyl acetoacetate and diethyl malonate provides an alternative method for preparing their a alkyl derivatives... 

There is a wide variety of dyes unique to the field of hair coloring. Successive N-alkylation of the nitrophenylenediamines has an additive bathochromic effect on the visible absorption to the extent that violet-blue dyes can be formed. Since the simple A/-alkyl derivatives do not have good dyeing properties, patent activity has concentrated on the superior A/-hydroxyalkyl derivatives of nitrophenylenediamines (29,30), some of which have commercial use (31). Other substituents have been used (32). A series of patents also have been issued on substituted water-soluble azo and anthraquinone dyes bearing quaternary ammonium groups (33). 

OC-All lation of Carbonyl Compounds and Derivatives. The organoborate iatermediates generated by the reaction of alkylboranes with carbanions derived from a-halocarbonyl compounds and a-halonitriles rearrange to give a-alkylated products. 

A AlI lation. 1-Substitution is favored when the indole ring is deprotonated and the reaction medium promotes the nucleophilicity of the resulting indole anion. Conditions which typically result in A/-alkylation are generation of the sodium salt by sodium amide in Hquid ammonia, use of sodium hydride or a similar strong base in /V, /V- dim ethyl form am i de or dimethyl sulfoxide, or the use of phase-transfer conditions. 

Another common process iavolves reaction with C=C or C=N species having adjacent CH2 or CH groups. Initial attack of the isocyanate is on the electron-rich center of the double bond with subsequent migration and iasertion of the CONR group iato the CH bond. Suitable reagents iaclude A/-alkylated acetamidines, 1-methyl dihydroisoquiaoline, and 2-methyl-2-oxa2oline [1120-64-5] (35). 

Low boiling isocyanates, such as methyl isocyanate [624-83-9] are difficult to prepare via conventional phosgenation due to the fact that the A/-alkyl carbamoyl chlorides are volatile below their decomposition poiat. Interestingly, A/-ethyl carbamoyl chloride decomposes at its boiling poiat whereas the A/-propyl carbamoyl chloride is thermoly2ed cleanly into isocyanate and hydrogen chloride. 

Naphthol is mainly used in the manufacture of the insecticide carbaryl (59), l-naphthyl A/-methyicarbamate/ iJ-2j5 - (Sevin) (22), which is produced by the reaction of 1-naphthol with methyl isocyanate. Methyl isocyanate is usually prepared by treating methylamine with phosgene. Methyl isocyanate is a very toxic Hquid, boiling at 38°C, and should not be stored for long periods of time (Bhopal accident, India). India has developed a process for the preparation of aryl esters of A/-alkyl carbamic acids. Thus l-naphthyl methylcarbamate is prepared by refluxing 1-naphthol with ethyl methylcarbamate and POCl in toluene (60). In 1992, carbaryl production totaled > 11.4 x 10 t(35). Rhc ne-Poulenc, at its Institute, W. Va., facihty is the only carbaryl producer in United States. 

A number of A/-acyl-. A/-alkyl-, and /V-arylamin on apbtbalenol sulfonic acids are used as couplers for a2o dyes. Examples of such intermediates are shown in Table 8. 

The (A/-alkylated) lactam of 8-aminonaphthalenecarboxylic acid (47) also is a valuable dye iatemiediate, eg, for cyclometbine-type dyes used for dyeiag polyacrylonitrile fibers and other synthetics. 1,8-Naphtholactams are prepared in high yield and purity by the reaction of naphtholactones with RNH2 (R = H, Cl—4 alkyl, cycloalkyl, or optionally substituted aryl) in aqueous medium, usually in the presence of bisulfite at 150°C over a period of 15 h (143). 

---