Halide benzyl

Benzylic halides that are secondary resemble secondary alkyl halides in that they undergo substitution only when the nucleophile is weakly basic If the nucleophile is a strong base such as sodium ethoxide elimination by the E2 mechanism is faster than substitution... 

Benzylic halides resemble allylic halides m the readiness with which they form carbocations On comparing the rate of S l hydrolysis m aqueous acetone of the fol lowing two tertiary chlorides we find that the benzylic chloride reacts over 600 times faster than does tert butyl chloride... 

Section 11 14 Benzylic carbocations are intermediates in SnI reactions of benzylic halides and are stabilized by electron delocalization... 

Section 1115 The simplest alkenylbenzene is styrene (C6H5CH=CH2) An aryl group stabilizes a double bond to which it is attached Alkenylbenzenes are usu ally prepared by dehydration of benzylic alcohols or dehydrohalogena tion of benzylic halides... 

Rearrangement is especially prevalent with primary alkyl halides of the type RCH2CH2X and R2CHCH2X Aluminum chloride induces ionization with rearrangement to give a more stable carbocation Benzylic halides and acyl halides do not rearrange... 

The methylation of N-methyl derivatives of maleic hydrazide gives in general O-alkylated products. The opposite results are obtained with benzyl halides as alkylating agents. In this case the O-benzyl derivative (71) is formed, which is then further benzylated to the lV,0-dibenzyl derivative (72). When ethyl chloroacetate is used, the direction of alkylation is dependent on pH. At pH above 8, O-alkylation occurs at pH below 8, N-alkylation takes place exclusively in neutral and acidic solutions only IV-alkylated products are formed. 

Various alkylating agents are used for the preparation of pyridazinyl alkyl sulfides. Methyl and ethyl iodides, dimethyl and diethyl sulfate, a-halo acids and esters, /3-halo acids and their derivatives, a-halo ketones, benzyl halides and substituted benzyl halides and other alkyl and heteroarylmethyl halides are most commonly used for this purpose. Another method is the addition of pyridazinethiones and pyridazinethiols to unsaturated compounds, such as 2,3(4//)-dihydropyran or 2,3(4//)-dihydrothiopyran, and to compounds with activated double bonds, such as acrylonitrile, acrylates and quinones. 

Pyrroles do not react with alkyl halides in a simple fashion polyalkylated products are obtained from reaction with methyl iodide at elevated temperatures and also from the more reactive allyl and benzyl halides under milder conditions in the presence of weak bases. Alkylation of pyrrole Grignard reagents gives mainly 2-alkylated pyrroles whereas N-alkylated pyrroles are obtained by alkylation of pyrrole alkali-metal salts in ionizing solvents. 

In many cases, substituents linked to a pyrrole, furan or thiophene ring show similar reactivity to those linked to a benzenoid nucleus. This generalization is not true for amino or hydroxyl groups. Hydroxy compounds exist largely, or entirely, in an alternative nonaromatic tautomeric form. Derivatives of this type show little resemblance in their reactions to anilines or phenols. Thienyl- and especially pyrryl- and furyl-methyl halides show enhanced reactivity compared with benzyl halides because the halogen is made more labile by electron release of the type shown below. Hydroxymethyl and aminomethyl groups on heteroaromatic nuclei are activated to nucleophilic attack by a similar effect. 

In general, benzyl ethers are prepared from a phenol by treating an alkaline solution of the phenol with a benzyl halide. ... 

The following benzyl halides were used PhCH2Br, 82% yield PhCH(CH3)Br, 33% yield (Ph)2CHBr, 50% yield 3,4-(MeO)2C6H3CH2Cl, 52% yield.. ... 

This method is particularly applicable to the more reactive benzyl halides which are easily hydrolyzed in the aqueous media usually employed for the metathetical reaction with alkali cyanides. For example, anisyl chloride treated with sodium cyanide in aqueous dioxane gives, as a by-product, 5-10% of anisyl alcohol as determined by infrared analysis. The use of anhydrous acetone not only prevents hydrolysis to the alcohol but also decreases the formation of isonitriles. This method was also applied successfully by the submitters to the preparation of -chlo-rophenylacetonitrile in 74% yield. 

A study of alkylations with a group of substituted benzyl halides and a range of Friedel-Crafts catalysts has provided insight into the trends in selectivity and orientation that accompany changes in both the alkyl group and the catalysts. There is a marked increase in substrate selectivity on going from / -nitrobenzyl chloride to /i-methoxybenzyl chloride. For example, with titanium tetrachloride as the catalyst, Aitoi Abenz increases from 2.5 to 97. This increase in substrate selectivity is accompanied by an increasing preference for para substitution. With /i-nitrobenzyl chloride, the ortho para ratio is 2 1 (the... 

A mechanism of this type permits substitution of certain aromatic and ahphatic nitro compounds by a variety of nucleophiles. These reactions were discovered as the result of efforts to explain the mechanistic basis for high-yield carbon alkylation of the 2-nitropropane anion by p-nitrobenzyl chloride. p-Nitrobenzyl bromide and iodide and benzyl halides that do not contain a nitro substituent give mainly the unstable oxygen alkylation product with this ambident anion ... 

Primary benzylic halides are ideal substrates for Sn2 reactions because they are very reactive toward good nucleophiles and cannot undergo competing elimination. 

However, it has recently been shown (42) that monomeric enamines such as 42 react normally to give the benzothiazoline salt (43) on alkylation with alkyl and benzyl halides. 

A fundamental problem in the alkylation of enamines, which is inherent in the bidentate system, is the competition between the desired carbon alkylation and attack at the nitrogen. With unactivated alkyl halides (3,267), this becomes especially serious with the enamines derived fromcycloheptan-one, cyclooctanone, cyclononanone, and enamines derived from aldehydes. Increasing amounts of carbon alkylation are found with the more reactive allyl and benzyl halides (268-273). However, with allyl halides one also observes increasing amounts of dialkylation of enamines. 

The formation of quaternary salts from benzyl halides and related compounds occurs readily and has been known for many years. More recently, Krohnke and co-workers, who have studied the reactions of many heterocyclic quaternary salts, reported the formation of 5 from pyridine and benzylidene dibromide on heating the reactants together for 1 hr at 100°. The salt is sufficiently stable to be recrystallized from methanol containing a trace of hydrogen bromide. Isoquinoline gives a similar salt. 

Nucleophilic substitution of the halogen atom of halogenomethylisoxazoles proceeds readily this reaction does not differ essentially from that of benzyl halides. One should note the successful hydrolysis of 4-chloromethyl- and 4-(chlorobenzyl)-isoxazoles by freshly precipitated lead oxide, a reagent seldom used in organic chemistry. Other halides, ethers, and esters of the isoxazole series have been obtained from 3- and 4-halogenomethylisoxazoles, and 3-chloro-methylisoxazole has been reported in the Arbuzov rearrangement. Panizzi has used dichloromethylisoxazole derivatives to synthesize isoxazole-3- and isoxazole-5-aldehydes/ ... 

Differences in solubility of the reactants may for example be utilized as follows. Sodium iodide is much more soluble in acetone than are sodium chloride or sodium bromide. Upon treatment of an alkyl chloride or bromide with sodium iodide in acetone, the newly formed sodium chloride or bromide precipitates from the solution and is thus removed from equilibrium. Alkyl iodides can be conveniently prepared in good yields by this route. Alkyl bromides are more reactive as the corresponding chlorides. Of high reactivity are a-halogen ketones, a-halogen carboxylic acids and their derivatives, as well as allyl and benzyl halides. 

The reaction works well with primary alkyl halides, especially with allylic and benzylic halides, as well as other alkyl derivatives with good leaving groups. Secondary alkyl halides give poor yields. Tertiary alkyl halides react under the usual reaction conditions by elimination of HX only. Nitriles from tertiary alkyl halides can however be obtained by reaction with trimethylsilyl cyanide 4 ... 

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