Hahdes alkyl, alkylation with

Ketenimines are usually prepared from carboxyHc acid derivatives such as amides and imino chlorides via elimination and from nitriles via alkylation with alkyl haHdes under strong basic conditions (21,64). 

Compounds, eg, phenacyl hahdes, ben2yl hahdes, alkyl iodides, or alkyl esters of sulfonic acids, react with DMSO at 100—120°C to give aldehydes (qv) and ketones (qv) in 50—85% yields (eq. 8) (41) ... 

Reaction of carbon disulfide with 2-phenyl-5(4//)-oxazolone 146 followed by S-alkylation with a methyl hahde gives 4-[bis(methylthio)methylene]-2-phenyl-5(4//)-oxazolone. The solvolysis and aminolysis of this compound have also been studied. ... 

The scaffold that would support such a tethered tris-NHC ligand could either be a CH-, a N- or a bigger moiety like a benzene ring. In each case, the scaffold carrying three alkyl hahdes is reacted with the appropriate substituted imidazole to generate the tris-imidazo-lium salt precursor (see Figure 3.134) [386,391,393],... 

The direct allylation of radical precursors (e.g., alkyl hahdes, thioacyl derivatives) with allyltributylstannane in the presence of an initiator represents a well-established protocol for carbon-carbon bond formation [29,30]. This methodology provides a convenient means for introducing an allyl group to the anomeric carbon of carbohydrates [31]. hi their recent work on the preparation of building blocks for C-glycoside synthesis, Postema and coworkers... 

Several methods, all based on carbon monoxide or metal carbonyls, have been developed for converting an alkyl halide to a carboxylic acid or an acid derivative with the chain extended by one carbon. When an alkyl hahde is treated with SbCls—SO2 at —70°C, it dissociates into the corresponding carbocation (p. 236). If carbon monoxide and an alcohol are present, a carboxylic ester is formed by the following route ... 

Sommelet reaction. Preparation of aldehydes from aralkyl or alkyl hahdes by reaction with hexamethylenetetramine followed by mild hydrolysis of the formed quaternary salt. 

Ethyl ketones. The reactions of alkyl hahdes (and tosylates) with Na Fe-(( 0)4 and ethylene in THF at 5 to 25° gives ethyl ketones in high yields (KO-95%). Intermediates (a)-(c) are probably involved. Actually, the hydrogen... 

The preparation of these salts is usually performed by a simple N-alkylation of 1-methylimidazole generating a l-alkyl-3-methylimidazolium cation followed by anion metathesis [27]. The synthesis can also start with imidazole, which is consecutively alkylated with alkyl hahdes (Scheme 3.5-9). The 1,3-dialkylimidazolium cations will be abbreviated throughout this section as [C Cylm], where Im stands for imidazolium and x and y are the number of the carbons of the alkyl chains. 

Keto esters represent interesting substrates that permit ready and various opportunities for further stmctural manipulation, but until 2002 only limited asymmetric a-alkylation procedures were developed [85]. In 2002, Dehmlow et al. [86] demonstrated the use of cinchonidinium bromide Ic in asymmetric a-alkylation of p-ketoester 24 when the corresponding benzylated product 29 (Scheme 8.11, entry 1) was obtained in excellent yield (97%), satisfying 46% ee. Better results in terms of enantioselectivity (up to 97% ee) were reported by Kim and co-workers [87], who showed the effectiveness of bulky cinchonine-derived catalysts IL in asymmetric a-alkylation of P-ketoesters(Scheme 8.11, entry 2). An asymmetric a-alkylation procedure with broad generahty in terms of the stmcture of P-ketoesters 25 and alkyl hahdes under PTC with C2-symmetric PTC L was developed by Maruoka and co-workers [88] (Scheme 8.11, entry 3). Further optimization led to the development of a reliable route for the asymmetric synthesis of not only a,a-dialkyl-P-hydroxy and p-amino esters, but also functionalized aza-cyclic a-amino esters [89], a-alkylated ketolactones [90], and functionalized a-benzoyloxy-P-ketoesters [91]. Shghtly changed catalyst XXV (Scheme 8.12) was also successfully used for the constmction of enantiomerically enriched various a-alkyl-a-fluoro-P-keto esters... 

Starting from scaffold 178 linked to Rink amide resin, two libraries of psolaren analogs (181 and 182) were prepared from a common o-dianilino intermediate 180. The benzoimidazole ring of psolaren analogs 181 was formed upon treatment of 180 with aryl isothiocyanates in the presence of Die, whereas for analogs 182 cyclization was carried out with l,T-thiocarbonyldiimidazole (TCD) followed by S-alkylation with alkyl hahdes in the presence of Af,Af-diisopropylethylamine. The unique spectral properties of these coumarin derivatives indicated that they may be useful in photochemotherapy. 

Alkyl halides can react with alkynyl Grignard reagents, but the use of TMEDA as reaction solvent is mandatory. Thus, alkynylation of a variety of alkyl hahdes proceeds smoothly with (2-trimethylsilylethynyl)magnesium reagents in the presence of 40mol% of Go(acac)3 in TMEDA at 25 °C [102]. Primary and secondary alkyl bromides or iodides are viable partners, unhke tertiary or benzyhc halides. The procedure tolerates several functional groups on the electrophihc partners including acetal and tosyl moieties as in 153 (Scheme 5.33). 

Secondary alkyl halides occupy a borderline region in which the nature of the nucleophile is the main determining factor in respect to the mechanism. Secondary alkyl hahdes usuaUy react with good nucleophiles by the Sn2 mechanism, and with weak nucleophiles by SnI. 

Active sites are formed by the reaction of chemisorbed metal alkyls with metal hahde on the crystal surface. 

Among these isomers, only the last two will atFord a tertiary alkyl hahde upon treatment with HBr. And among these two alkenes, only the latter will undergo ozonolysis to produce a compound with three carbon atoms and another compound with two carbon atoms. Now that we have identified the starting alkene, we can draw the products B-F, as shown here ... 

Another similar example concerns the alkylation of enamines. This reaction works well with reactive a-halocarbonyl compounds (frames 175ff) but simple alkyl hahdes often react on nitrogen ... 

Strategy Problem 1 The wrong substitution pattern . Making aromatic compounds m-substituted with two o -directing groups is always a problem. What strategies can you suggest An example (TM 412) is the alkyl hahde used in the synthesis of some steroids. 

Partial but not complete loss of optical activity m S l reactions probably results from the carbocation not being completely free when it is attacked by the nucleophile Ionization of the alkyl halide gives a carbocation-hahde ion pair as depicted m Figure 8 8 The halide ion shields one side of the carbocation and the nucleophile captures the carbocation faster from the opposite side More product of inverted configuration is formed than product of retained configuration In spite of the observation that the products of S l reactions are only partially racemic the fact that these reactions are not stereospecific is more consistent with a carbocation intermediate than a concerted bimolecular mechanism... 

Nitdles may be prepared by several methods (1). The first nitrile to be prepared was propionitdle, which was obtained in 1834 by distilling barium ethyl sulfate with potassium cyanide. This is a general preparation of nitriles from sulfonate salts and is referred to as the Pelou2e reaction (2). Although not commonly practiced today, dehydration of amides has been widely used to produce nitriles and was the first commercial synthesis of a nitrile. The reaction of alkyl hahdes with sodium cyanide to produce nitriles (eq. 1) also is a general reaction with wide appHcabiUty ... 

Arylation of Aromatic Compounds. In contrast to Friedel-Crafts alkylations, arylations of aromatics are not as well known, and usually require drastic conditions. They iaclude (/) dehydrogenating condensation (SchoU reaction) (2) arylation with aryl haUdes and (J) arylation with dia2onium hahdes. 

The direct reaction of other alkyl chlorides, such as butyl chloride, results in unacceptably low overall product yields along with the by-product butene resulting from dehydrochlorination. AH alkyl haHdes having a hydrogen atom in a P- position to the chlorine atom are subject to this complication. 

Particular drawbacks of using alkylsiHcon and alkyltin haHdes with AlCl for the cationic polymerization of terpenes are low yields and the fact that they require rigorously dried feeds (<50 ppm H2O) to be effective. Increased water content results in lower yields and lower softening points (85). Catalyst systems comprised of AlCl with antimony haHdes in the presence or absence of a lower alkyl, alkenyl, or aralkyl haHde are particularly effective in systems containing up to 300 ppm H2O (89,90). Use of 2—12 wt % of a system composed of 2—3 parts AlCl, 0.7—0.9 parts SbCl, and 0—0.2 parts of an organic... 

Alkyl hahdes in the presence of silver oxide react with alkyl malates to yield alkoxy derivatives of succinic acid, eg, 2-ethoxysuccinic acid, H00CCH2CH(0C2H )C00H (12,13). A synthetic approach to produce ethers of malic acid is the reaction of malic esters and sodium alkoxides which affords 2-alkoxysuccinic esters (14). 

The porphyrin ligand can support oxidation states of iron other than II and III. [Fe(I)Por] complexes are obtained by electrochemical or chemical reduction of iron(II) or iron(III) porphyrins. The anionic complexes react with alkyl hahdes to afford alkyl—iron (III) porphyrin complexes. Iron(IV) porphyrins are formally present in the carbene, RR C—Fe(IV)Por p.-carbido, PorFe(IV)—Fe(IV)Por nitrene, RN—Fe(IV)Por and p.-nittido, PorFe(IV)... 

Isopropylnaphthalenes produced by alkylation of naphthalene with propjdene have gained commercial importance as chemical intermediates, eg, 2-isopropylnaphthalene [2027-17-OJ, and as multipurpose solvents, eg, mixed isopropylnaphthalenes. Alkylation of naphthalene with alkyl haUdes (except methyl hahdes), acid chlorides, and acid anhydrides proceeds in the presence of anhydrous aluminum chloride by Friedel-Crafts reactions (qv). The products are alkylnaphthalenes or alkyl naphthyl ketones, respectively (see Alkylation). 

Phosphonium salts are readily prepared by the reaction of tertiary phosphines with alkyl or henzylic haHdes, eg, the reaction of tributylphosphine [998-40-3] with 1-chlorobutane [109-69-3] to produce tetrabutylphosphonium chloride [2304-30-5]. 

All lation. Alkylating agents such as diaLkyl sulfates and alkyl hahdes react with ahphatic amine oxides to form trialkylalkoxyammonium quaternaries. For example (33), methyl iodide reacts with trimethyl amine oxide to form trimethylmethoxyammonium iodide... 

Method 7. Alkyl haHde amination reaction of ammonia or alkylamine with an alkyl haHde. 

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