Benzyl chloride, neutral

The benzyl group has been widely used for the protection of hydroxyl functions in carbohydrate and nucleotide chemistry (C.M. McCloskey, 1957 C.B. Reese, 1965 B.E. Griffin, 1966). A common benzylation procedure involves heating with neat benzyl chloride and strong bases. A milder procedure is the reaction in DMF solution at room temperatiue with the aid of silver oxide (E. Reinefeld, 1971). Benzyl ethers are not affected by hydroxides and are stable towards oxidants (e.g. periodate, lead tetraacetate), LiAIH, amd weak acids. They are, however, readily cleaved in neutral solution at room temperature by palladium-catalyzed bydrogenolysis (S. Tejima, 1963) or by sodium in liquid ammonia or alcohols (E.J. Rcist, 1964). 

N-Alkylations, especially of oxo-di- and tetra-hydro derivatives, e.g. (28)->(29), have been carried out readily using a variety of reagents such as (usual) alkyl halide/alkali, alkyl sulfate/alkali, alkyl halide, tosylate or sulfate/NaH, trialkyloxonium fluoroborate and other Meerwein-type reagents, alcohols/DCCI, diazoalkanes, alkyl carbonates, oxalates or malon-ates, oxosulfonium ylides, DMF dimethyl acetal, and triethyl orthoformate/AcjO. Also used have been alkyl halide/lithium diisopropylamide and in one case benzyl chloride on the thallium derivative. In neutral conditions 8-alkylation is observed and preparation of some 8-nucleosides has also been reported (78JOC828, 77JOC997, 72JOC3975, 72JOC3980). 

Neutral Hydrolysis Studies. Investigations of neutral (pH-independent) hydrolysis kinetics in sediment/water systems were conducted for three organophosphorothioate insecticides (chlorpyrifos, diazinon and Ronnel), 4-(p-chlorophenoxy)butyl bromide, benzyl chloride, and hexachlorocyclopentadiene. 

Benzyl chloride hydrolysis proceeds via a third mechanism (Sj.1). Results of studies of benzyl chloride hydrolysis ( 1) in distilled water and EPA-13 and EPA-2 sediment/water systems are summarized in Table V. Results for this compound include only overall first-order disappearance rate constants, but the data clearly show that the hydrolysis rate is independent of the fraction sorbed to sediment. Thus, the conclusion is again made that neutral hydrolysis proceeds via similar rate constants in both the aqueous and sediment-sorbed phases. 

In a mechanistically similar process, the neutral palladium(II) dipyridylamine complex (24), obtained by deprotonation of complex (23), underwent reaction with benzoyl chloride to give the substituted complex (25) together with some free ligand (Scheme 8).33 This particular reaction sequence could not be generalized because of the relative instability of other metal complexes related to compound (24). However, a more extensive series of electrophilic substitutions could be carried out on the neutral complex (26), which displayed ambident nucleophilic behaviour by reaction with benzyl chloride and benzoyl chloride at nitrogen and reaction with benzenediazonium fluoroborate at carbon (Scheme 9). 

Macrocyclic receptors have also been found to complex neutral substrates,21 and complexes of both variable and exact stoichiometries have been prepared. The latter category includes acidic CH— and NH— or polar neutral molecules, such as acetonitrile, nitromethane, benzyl chloride and dimethylmalonitrile. X-Ray data indicate complex formation to be mainly a result of hydrogen bonding and dipole-dipole interactions. Section 21.3.8 contains a more detailed treatment of these complexes. 

To separate malonic ester still present and which amounts to 15 to 20 per cent, it must be converted into the higher boiling derivative, benzyl-malonic ester. For this purpose half a gram of sodium in alcohol is added to every 20 gms. of the oil collected, and to this mixture 2 5 gms. of benzyl chloride is added and the whole heated until neutral. 

Nitrobenzyl halides are reduced in a 1 e-process to radical anions, which rapidly lose halide ion to form the neutral nitrobenzyl radical. The rates for this dissociation were calculated from cyclic voltammetry data to be k = 2,5 for m-nitrobenzyl chloride and k = 2 109 secfor o-nitrobenzyl bromide. The nitrobenzyl radicals predominantly dimerize (90%), whereas a small amount yields nitrotoluenes (< 10%) by hydrogen abstraction 4541. From a series of substituted benzyl bromides those with the more positive reduction potential form bibenzyl in 25—74% yield, whereas from the less easily reducible ones dibenzyl-mercury derivatives are obtained (50—60%) 485). Reduction of benzyl chloride at the plateau of the first wave yields dibenzylmercury 4 By reduction of diphenyliodonium hydroxide at -1,6 V 51% diphenylmercury is obtained 488 ... 

Why is benzyl fluoride in alkaline or neutral media hydrolyzed more slowly than benzyl chloride and yet in acidic media is hydrolyzed much faster than benzyl chloride ... 

In the hydrolysis of benzyl chloride, the leaving group is chloride anion. When benzyl fluoride is hydrolyzed in alkaline or neutral media, the leaving group is fluoride anion, which is a worse leaving group than chloride anion because the carbon-fluorine bond is much stronger than the carbon-chlorine bond 443 kJ (106 kcal/mol) vs. 328 kJ (78 kcal/ mol), respectively. 

Benzyl Chloride. The principal method for producing benzyl chloride involves the photochlorination of toluene, followed by neutralization and distillation. In 1999, 75 million lb of benzyl chloride were produced in the United States. About two-thirds was used to manufacture benzyl phthalates (mainly butyl benzyl phthalate), which are widely used as plasticizers. The other use was to make benzyl quarts. Benzyl chloride can also be used as raw material in the manufacture of benzyl alcohol, for use in photography, perfumes, and cosmetics. The production has increased considerably in Western Europe because of the greater use in solvents such as benzyl esters. But the U.S. production was stopped in 1999. 

The identification of the base is accomplished as follows. Since an aminophenol is formed in the stannous chloride reduction, the original structure was most probably that of an ester or an ether. 8 grams of the base is boiled with 80 cc. 20 per cent hydrochloric acid in a flask fitted with a downward condenser and steam is introduced simultaneously. A lachrymatory liquid distills. It is heavier than water and boils at 175°C. The compound, when warmed with silver nitrate, produces silver chloride. It is oxidized very rapidly by neutral permanganate solution to produce benzoic acid, m.p. 121°. The distillate is therefore benzyl chloride. 

Perimidine has an acidic NH proton and therefore behaves differently from pyrimidine and quinazoline. The product is a neutral molecule. Like imidazoles, perimidines are best A-alkylated in alkaline media (79) in an inert atmosphere. Alkylation with primary alkyl bromides or iodides can be performed in an alcoholic solution. Dimethyl sulfate is recommended for methylation. Yields drop with secondary halides. A-Substitution reactions are sensitive to steric interference from 2-and 4(9)-substituents 2-alkyl or aryl derivatives can be methylated but not alkylated by benzyl chloride or isopropyl, allyl or phenacyl bromides. 4(9)-Substituted perimidines are preferentially alkylated at the remote nitrogen. 

The inability of such photolyzate solutions to hydroborate 1-octyne rules out the presence of neutral boron hydrides. However, the detection of HD, upon the work-up with DOAc, and the formation of undeuterated toluene, upon treatment of the photolyzate with benzyl chloride and deuterolytic work-up, clearly support the presence of borohydrides, such as 45 (6). Finally, evidence supporting the generation of sodium diphenylborate(I) (46) or a similar product was obtained by conducting the photolysis in the presence of diphenylacetylene. Since monomeric 46 is formally isoelectronic with a carbene, adducts like 48... 

Instead, two new and different mechanisms become possible. Either the leaving group goes first and the nucleophile comes in later, or the two events happen at the same time. The first of these possibilities you will learn to call the 5, 1 mechanism. The second mechanism, which shows how the neutral carbon atom can accept electrons provided it loses some at the same time, you will learn to call the 8 2 mechanism. You will see later that both mechanisms are possible with this molecule, benzyl chloride. 

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