Benzyl halides reaction with

The reactivities of alkyl halides are in the sequence RI > RBr > RCl and MeX > EtX > PrX. Benzyl halide reactions with tin do not require catalysts (equation 2). For less reactive halides, the catalysts and promoters employed include metals (sodium, magnesium, zinc, or copper), Lewis bases (amines, triorganophosphines and -stibines, alcohols, or ethers), iodides, and onium salts (R4MX). The use of tin-sodium alloys can result in tri- or tetraorganotin products. Electrochemical synthesis has also been reported, e.g. the formation of R2SnX2 from the oxidation of anodic tin by RX in benzene solution and the formation of R4Sn from RI (R = Me or NCCH2CH2) and cathodic tin. 

A related process involves fluoride-induced desilylation in HMPA at room temperature of benzyldi-methyl(trimethylsilylmethyl)ammonium halides (20) to (21 62-84% yields R = H, 2-Me, 4-Me, 2-C1,4-Cl, 4-OAc X = Cl, Br).9 100 Compunds (20) were prepared by reaction of the corresponding benzyl halide derivatives with (dimethylaminomethyl)trimethylsilane, Me3SiCH2NMe2. The product of Stevens rearrangement (22) formed competitively and predominantly from precursors (20) having strong electron-withdrawing substituents (R = 2-COMe, 2-CN, 4-CN, 2-NO2, and 4-NO2).100... 

Substituted benzyl halides react with hexamine in boiling alcohol to form addition compounds which decompose on heating with water to give aldehydes. " An excellent discussion of the reaction has been presented, and improvements in the conditions have been made. Aqueous acetic acid (1 1) is recommended as solvent for the entire process, and there is no need to isolate the intermediate salt. The procedure is illustrated by the synthesis of 1-naphthaldehyde (82%). In other instances, the addition compound is first ptrepared in chloroform solution, isolated, and then decomposed with water or dilute acetic acid, as in the synthesis of 2-thiophenaldehyde (53%). ... 

It is interesting to note that the hydrolysis of unhindered benzoyl chlorides is not catalyzed by acids, but benzoyl fluoride is acid catalyzed and follows Kq (Bevan and Hudson, 1953). Similarly, acid catalysis of benzyl fluoride hydrolysis which follows occurs (Swain and Spalding, 1960), but no acid catalysis of benzyl chloride hydrolysis is known. Furthermore, benzyl halide reactions show non-linear pa correlations (Hudson and Klopman, 1962 Hill and Fry, 1962 Swain and Langsdorf, 1951). Although much less work has been carried out on benzoyl halides, it would appear then that nucleophilic reactions with benzoyl halides resemble, in many respects, nucleophilic reactions with benzyl systems, including the considerable uncertainty as to the S l or bimolecular nature of these reactions (Thornton, 1964). 

Another synthesis of isoquinolines in which two ring bonds are formed involves the reaction of benzyl halides (74) with the sodium salt of N-(tosylamino)acetaldehyde dimethyl acetal. Treatment of the intermediate (75) with hydrochloric acid results both in ring-closure and aromatization (Scheme 48). ... 

Benzyl halides react with tin powder, e.g., in aqueous suspension at 100°, giving very good yields of tribenzyltin halides 431 and reaction with 4-iso-propylbenzyl chloride is similar.432 The influence of the solvent on interaction of benzyl chloride with tin powder has been investigated in detail.433... 

Michaelis-Arbuzov reactions have been carried out with tribenzyl phosphite and mixed alkyl dibenzyl phosphites (PhCH20)2P0R. A trace of an alkyl halide causes the former to isomerize to the predicted dibenzyl benzylphosphonate, but when the mixed phosphites are treated with the halide R X, loss of benzyl halide occurs with the formation of (PhCH20)(R0)P(0)R. The high reactivity of the systems led to the formation of several oligophosphonates. Carbohydrate-like 1,2-oxaphosphori-nanes have been prepared from 2,3-dimethoxybutane 1,4-dihalides and PhP(OEt)2 as mixtures of diastereoisomers (compare the formation of 57) ... 

The picolinium salts (216) obtained by reactions of the picolines (215) with a-halogenoketones, and also with a-halogenoesters and a-halogenoni-triles (and even those from benzyl halides), react with a-dicarbonyl compounds in the presence of base to give quinolizinium salts (217) as shown in Scheme 50 salts derived from 1-methylisoquinoline similarly gave... 

In the presence of a Lewis acid, silyl enol ethers can be alkylated with reactive secondary halides, such as substituted benzyl halides, and with chloromethylphenyl sulfide (ClCH2SPh), an activated primary halide. Thus, reaction of the benzyl chloride 10 in the presence of zinc bromide with the trimethylsilyl enol ether derived from mesityl oxide allowed a short and efficient route to the sesquiterpene ( )-ar-turmerone (1.22). Reaction of ClCH2SPh with the trimethylsilyl enol ethers of lactones in the presence of zinc bromide, followed by 5-oxidation and pyrolytic ehmination of the resulting sulfoxide (see Section 2.2), provides a good route to the a-methylene lactone unit common in many cytotoxic sesquiterpenes (1.23). Desulfurization with Raney nickel, instead of oxidation and elimination, affords the a-methyl (or a-alkyl starting with RCH(Cl)SPh) derivatives. ... 

Aryl chlorides typically do not react under these conditions. However, Miyaura has been able to extend the scope of this reaction to include aryl chlorides by changing the catalyst system to Pd(dba)2 and PCys and replacing pinacolborane with bis(pinacolato)diboron. Vinyl iodides and trifiates undergo borylation with pinacolborane under similar conditions in the presence of triphenylarsine (AsPEb) (eq 17). Benzylic halides react with pinacolborane in the presence of PdCl2, PPhs, and N,N-diisopropylethyl amine (eq 18). Borylation of allylic halides in the presence of Pt(dba)2, AsPhs, and EtsN leads to highly regio-and stereoselective allylboronates (eq 19). 

Table 7.5 3-Arylpropanenitriles (3) prepared by the reaction of benzyl halides (1) with bromoacetonitrile (2 = nickel). ... 

Certain aryl and benzyl halides react with primary and secondary amines yielding the corresponding secondary and tertiary amines, in addition to hydrogen halide, much in the same shion as described in section II.B.4. However, by virtue of the electronegative nature of the reagents, the reaction does not proceed further up to quatemisa-tion as with the previous case, neither does it yield quaternary ammonium compounds with tertiary amines. 

Hirao, A., Hayashi, M., and Matsuo, A. (2002c) Synthesis of branched polymers by means of living anionic polymerisation. 10. Synthesis of well-defined heteroarm star-branched polymers by coupling reaction of chain-functionalized polystyrenes with benzyl halide moieties with Uving anionic polymers of tert-butyl methacrylate. Polymer, 43,7125-7131. 

Lithium dialkylamides of hindered amines can generate aryl-substituted car-benes from benzyl halides. Reaction of a,a-dichlorotoluene or a,a-dibromotoluene with potassium t-butoxide in the presence of 18-crown-6 generates the corresponding a-halophenylcarbene. The relative reactivity data for carbenes generated under these latter conditions suggest that they are free. The potassium cation would be expected to be strongly solvated by the crown ether and is evidently not involved in the carbene-generating step. 

One type of o-aminobenzyl anion synthon is a mixed Cu/Zn reagent which can be prepared from o-toluidines by / i.s-trimethylsilylation on nitrogen, benzylic bromination and reaction with Zn and CuCN[l]. Reaction of these reagents with acyl halides gives 2-substituted indoles. 

Reaction with hydrogen halides (Sec tion 4 7) The order of alcohol reactiv ity parallels the order of carbocation staiiility RjC" > R2CH > RCHj" > CHj" Benzylic alcohols react readily... 

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. 

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 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 ... 

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 ... 

This reaction, which is named after W. Williamson, is the most important method for the synthesis of unsymmetrical ethers 3. For this purpose an alkoxide or phenoxide 1 is reacted with an alkyl halide 2 (with R = alkyl, allyl or benzyl). Symmetrical ethers can of course also be prepared by this route, but are accessible by other routes as well. 

Reaction of dibenzylamine with ethylene oxide affords the amino alcohol, 82. Treatment of that product with thionyl chloride gives the a-sympathetic blocking agent, dibenamine (83). (Condensation of phenol with propylene chlorohydrin (84) gives the alcohol, 85. Reaction with thionyl chloride affords the chloride (86). Use of the halide to alkylate ethanolamine affords the secondary amine (87). Alkylation of this last with benzyl chloride... 

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