By Reaction with Alkyl Halides

Pyrrolethiols, readily obtained from the corresponding thiocyanates by reduction or treatment with alkali, rapidly oxidize to the corresponding disulfides. They are converted into thioethers by reaction with alkyl halides in the presence of base. Both furan- and thiophene-thiols exist predominantly as such rather than in tautomeric thione forms. 

The triazole 76, which is more accurately portrayed as the nucleophilic carbene structure 76a, acts as a formyl anion equivalent by reaction with alkyl halides and subsequent reductive cleavage to give aldehydes as shown (75TL1889). The benzoin reaction may be considered as resulting in the net addition of a benzoyl anion to a benzaldehyde, and the chiral triazolium salt 77 has been reported to be an efficient asymmetric catalyst for this, giving the products (/ )-ArCH(OH)COAr, in up to 86% e.e. (96HCA1217). In the closely related intramolecular Stetter reaction e.e.s of up to 74% were obtained (96HCA1899). 

Electroreduction of the cationic Rh(IlI) complex [Rh(Por)(MeNFl2)2l in CH2CI2 followed by reaction with alkyl halides has been utilized to form a-alkyl products. The reaction scheme proposed for this reaction was one-electron reduction of Rh(lll) to form Rh(Por)-. This can either dimerize or attack the carbon atom of the alkyl halide RCH2X, the latter step involving elimination of either X- or 2t7.2.ix reactions of Co(ll) and Fe(II) porphyrins M(Por) with... 

The nitrogen atom in quinolizidine derivatives behaves as a tertiary amine and hence it can undergo quaternization by reaction with alkyl halides. For instance, berberine derivative 101 was transformed into 102 by treatment with 3-iodopropanol followed by anion exchange. Compound 102 was then transformed into intermediate 103, which was employed as a precursor for the the preparation of bis-ammonium salt 104 (Scheme 10). This compound showed ultrashort curare-like activity in rhesus monkeys <2001JOC3495>. 

Friedeb Crafts reaction Anisole undergoes Friedel-Crafts reaction, i.e., the all rl and acyl groups are introduced at ortho and para positions by reaction with alkyl halide and acyl halide in the presence of anhydrous alurntnlurn chloride (a Lewis acid) as catalyst. 

N-Alkylation of oxazolo[4,5-4]pyridines can be achieved in a number of ways. Viaud et al. have reported direct N-alkylation by reaction with alkyl halides (Equation 27 Table 23) or Michael condensation with a range of olefins (Equation 28 Table 24) <1996TL2409>, both methods affording the desired products in good yields. 

Unsymmetrically -substituted borazines can be prepared by the reaction of IV-substituted borazines or h-trihalogeno-N-substituted borazines and the appropriate amount of Grignard reagent (94). Borazines unsymmetrically substituted on nitrogen have been prepared by the reaction of Hthium borohydride and ammonium chloride and alkyl ammonium chlorides (105,106), and by Uthiation of B- trime thylb o r azine followed by reaction with alkyl halides (107). 

Potassium phthalimide is a "NH2-synthon which allows the preparation of primary amines by reaction with alkyl halides. After alkylation, the phthalimid is not nucleophile and does not react anymore. Product is cleaved by reaction with base or hydrazine, which leads to a stable cyclic product. 

Phenols can be converted into esters by reaction with acid chlorides or acid anhydrides and into ethers by reaction with alkyl halides in the presence of base (Following fig.). These reactions can be done under milder conditions than those used for alcohols due to the greater acidity of phenols. Thus phenols can be converted to phenoxide ions with sodium hydroxide rather than metallic sodium. 

Esterification. Carboxylic acids can be esterified by reaction with alkyl halides and DBU in benzene at 25 or 80° (equation I). The reaction is widely applicable to hindered or unstable acids and to BOC- or CBZ-protected amino atids. Yields are invariably high. Triethylamine is of less value as the base. Presumably the hydrogen-bonded complex of DBU and the acid plays a significant role in the reaction. The DBU can be recovered by treatment of the hydrohalide with sodium hydroxide. ... 

The typical reactions of the alcohol group include their conversion to ethers and esters by reaction with alkyl halides and with acid chlorides or anhydrides, respectively (Scheme 6.2). The benzyl ether group is readily cleaved by hydrogenolysis and is often used as a protecting group for alcohols. Primary alcohols are oxidized initially to the aldehyde and then to the carboxylic acid. 

Cysteine peptides may be converted to sulfonium derivatives by reaction with alkyl halides. The resulting sulfonium salts undergo /3-elimina-... 

Sodium hydrogen sulfide can be used for the preparation of thiols (19) by reaction with alkyl halides. A large excess of sodium hydrogen sulfide must be employed to avoid formation of the dialkyl sulfide (Scheme 17) (see Chapter 4, p. 41). 

Enolates can be alkylated by reaction with alkyl halides (in an SN2 reaction with primary and secondary alkyl halides). These reactions produce new carbon-carbon bonds. 

By reaction with alkyl halides, esters of sulfonic and carbonic acids, trimethy-loxonium tetrafluoroborate, diazo compounds, Mannich or Mitsunobu conditions or miscellaneous reagents. Methyl iodide is a versatile and effective methylating reagent that can be used at room temperature, at moderate temperatures in a tightly closed vessel or at high temperatures in an autoclave. 2,4-Dihydropyrazol-3-one 1 was methylated at N1 with sodium hydride in boiling 1,4-dioxane followed by methyl iodide at room temperature. l,2-Dihydropyrazol-3-one 2 was obtained in 59% yield (79AP853) (Scheme 1). 

Treatment of 1,3-diketones, such as CH3COCH2COCH3, with two equivalents of sodamide or potassium amide in liquid ammonia followed by reaction with alkyl halides gives the homologues in good yields [5,6] e.g. ... 

As sources of nucleophilic carbon, enolates can be alkylated at the a carbon by reaction with alkyl halides. 

Trimethyl tetrathiophosphate heated 12 hrs. in a closed flask on a water bath with a 28% soln. of trimethylamine in anhydrous acetone tetramethyl-ammonium dimethyl tetrathiophosphate. Y 85%. — The salts produced give mixed esters by reaction with alkyl halides. Also cleavage of trimethyl trithiol-phosphate s. P. Ghabrier and T. N. Thanh, G. r. 261, 2229 (1965). 

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