Halides, alkyl higher

Because of the substituent effect just described, allyl and benzyl halides generally react with nucleophiles according to an SN2 mechanism. This occurs even though the SN1 reactivity of allyl and benzyl halides is higher than that of nonconjugated alkylating agents (see Section 2.5.4). 

Direct Reaction of Zn with Alkyl Halides. The direct insertion see Insertion) reaction of Zn metal into alkyl halides - alkyl iodides being the ideal snbstrates - is a nseful reaction to prepare simple or polyfunctional organozinc halide compounds (equation 1). With primary alkyl iodides, the reaction requires an excess of Zn dnst (ca. 3 eqniv), previonsly treated with few mol % of 1,2-dibromoethane and TMSCl, and a temperature of 40 °C in THF. In these conditions, secondary alkyl iodides react at room temperatnre and benzylic and allylic bromides at 0 °C. The insertion see Insertion) into less activated C-X bonds may reqnire more reactive forms of zinc (Riecke zinc), higher temperatures, or the use of polar see Polar Compounds) solvent or cosolvent. 

Alkyl halides have higher bp s and mp s than alkanes having the same number of carbons. 

Organohalides, such as iodoalkanes, alkyl chloroacetates and benzyl halides, which are highly susceptible to nucleophilic attack, are readily converted to esters by reaction with carbon monoxide and an cohol in the presence of a base using Na[Co(CO)4] as catalyst (equation 30). Reactions proceed under mild conditions (25 C, 1 bar CO) and very good yields and selectivities can be obtained. With less reactive halides, however, higher temperatures are required leading to isomerization of the intermediate al-kylcobalt complex and hence to a mixture of carbonylated products. 

Triphenylphosphine imines, such as (188), are readily alkylated, the salt decomposing on hydrolysis to the secondary amine hydrochloride, as shown in Scheme 107 alkylating agents are limited to methyl and ethyl halides, as higher alkyl halides undergo preferential elimination. ... 

Methyl iodide ethyl bromide ethyl iodide, higher alkyl halides, chloroform, iodoform, carbon tetrachloride, chlorobenzene, bromobenzene, iodobenzene, benzyl chloride (and nuclear substituted derivatives)... 

Higher alcohols (> C3) react comparatively slowly with sodium because of the slight solubility of the sodium alkoxide in the alcohol a large excess (say, 8 mols) is therefore employed. The mixed ether is distilled off, and the process (formation of alkoxide and its reaction with the alkyl halide) may be repeated several times. The excess of alcohol can be recovered. cj/cloAliphatic alcohols form sodio compounds with difficulty if small pieces... 

The higher homologues of propyne, e.g. 1-decyne, can be obtained in a similar way. Starting from 1-butyne and its homologues, alkylation with alkyl halides leads to 1-alkynes with a branched substituent. 

Regardless of the alkyl halide raising the temperature increases both the rate of substitution and the rate of elimination The rate of elimination however usually increases faster than substitution so that at higher temperatures the proportion of ehm mation products increases at the expense of substitution products... 

Primary and secondary alkyl halides may be converted to the next higher carboxylic acid by a two step synthetic sequence involving the preparation and hydrolysis of nitriles Nitnles also known as alkyl cyanides are prepared by nucleophilic substitution... 

IV-Methylated pyridazinones can be obtained from 3,6-dialkoxypyridazines by treatment with alkyl halides or dialkyl sulfates. Methyl iodide and dimethyl sulfate are most frequently used. According to the proposed mechanism, an intermediate quaternary pyridazinium salt is formed, followed by elimination of a group R from the alkoxy group. At higher temperature, l,2-dimethylpyridazine-3,6(l//,2//)-dione is formed with dimethyl sulfate. 

The direct process is less flexible than the Grignard process and is restricted primarily to the production of the, nevertheless all-important, methyl- and phenyl-chlorosilanes. The main reason for this is that higher alkyl halides than methyl chloride decompose at the reaction temperature and give poor yields of the desired products and also the fact that the copper catalyst is only really effective with methyl chloride. 

Triflates of aluminum, gallium and boron, which are readily available by the reaction of the corresponding chlorides with triflic acid, are effective Fnedel-Crafis catalysis for alkylation and acylation of aromatic compounds [119, 120] Thus alkylation of toluene with various alkyl halides m the presence of these catalysts proceeds rapidly at room temperature 111 methylene chloride or ni-tromethane Favorable properties of the triflates in comparison with the correspond mg fluorides or chlorides are considerably decreased volatility and higher catalytic activity [120]... 

It s reasonable to ask why one would prepare a ketone by way of a keto ester (ethyl acetoacetate, for example) rather than by direct alkylation of the enolate of a ketone. One reason is that the monoalkylation of ketones via their enolates is a difficult reaction to cany out in good yield. (Remember, however, that acylation of ketone enolates as described in Section 21.4 is achieved readily.) A second reason is that the delocalized enolates of (3-keto esters, being far- less basic than ketone enolates, give a higher substitution-elimination ratio when they react with alkyl halides. This can be quite important in those syntheses in which the alkyl halide is expensive or difficult to obtain. 

Reaction of alkyl halides 1 with hexamethylenetetramine 2 (trivial name urotropine) followed by a hydrolysis step, leads to formation of primary amines 3 free of higher substituted amines. This method is called the Delepine reaction, a comparable method is the Gabriel synthesis. 

The first SN2 reaction variable to look at is the structure of the substrate. Because the S, j2 transition state involves partial bond formation between the incoming nucleophile and the alkyl halide carbon atom, it seems reasonable that a hindered, bulky substrate should prevent easy approach of the nucleophile, making bond formation difficult. In other words, the transition state for reaction of a sterically hindered alkvl halide, whose carbon atom is "shielded" from approach of the incoming nucleophile, is higher in energy... 

The present procedure seems to be a general one for producing alkyl halides from acids. To aid in isolating higher-boiling or solid products, solvents such as carbon tetrachloride and cyclohexane can be used.7 In preparing a solid, the mercuric halide can be removed by extraction with 5% potassium iodide. 

A proton can be removed from an allylic ether by treatment with an alkyllithium at about -70°C [at higher temperatures the Wittig rearrangement (18-22) takes place] to give the ion 130, which reacts with alkyl halides to give the two products... 

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