Phenethyl chloride

Besides benzyl chloride, methyl- and/or chlorine-substituted benzyl chlorides, phenethyl chloride, etc. are also successfully employed to give 2 -diaralkylaminofluorans in excellent yield. However, aryl halides such as chlorobenzene and bromobenzene hardly enable the reaction, though aryl iodides such as iodobenzene give 2 -diarylaminofluorans in low yield. 

Phenacyl chloride, c31 Phenazone, a299 1,2,4-Phenenyl triacetate, tl 93 Phenethyl acetate, pill Phenethyl alcohol, pi 10 sec-Phenethyl alcohol, ml49 Phenethylamine, pi 12 Phenethyl bromide, b334 Phenethyl chloride, cl28 Phenetole, e36... 

The synthesis of the right-hand fragment of ziprasidone started with a Wolff-Kishner reduction of isatin 43 to give the oxmdole 44 (Scheme 14). Friedel-Crafts acylation with chloroacetyl chloride afforded aryl ketone 45, which was reduced with triethylsilane in trifluoroacetic acid to the phenethyl chloride 46. The two fragments were joined by alkylation of 40 with 46 in the presence of Nal and Na2CO3 to give ziprasidone (4) in low yield. The yield of the coupling step was improved dramatically when the reaction was conducted in water (Scheme 15). 

Fluoride chloride exchange of 1 -chlorooctane (3) with potassium fluoride, catalyzed by tetra-butylammonium bromide gives higher yields (72%) of 1-fluorooctane (4) in the presence of formamide than those reactions conducted in the presence of water.57 In the case of 1-bro-mooctane, benzyl chloride or phenethyl chloride, fluoride halide exchange gives only a yield of < 50%. 

Under comparable conditions the corresponding alkylations of diphenylacetonitrile with a-phenethyl chloride and benzhydryl chloride have been effected to form 2,3,3-triphenylbutyronitrile and 2,2,3,3-tetraphenylpropionitrile in yields of 88 and 96% respectively.2... 

Phenethyl bromide, b283 Phenethyl chloride, cl08 / -Phenetidine, e24 Phenetole, e28 Phenoxyacetone, p74 4-Phenoxybutyl bromide, b243... 

Alkylation, of 2-acetamidothiazoles, 35, 37 with alkali amides, 34, 35 of alkylaminothiazole, 34 with alcohols, 47, 80, 90 of aminothiazoles, with alcohols, 38 with benzyl chloride. 33 with chloracetic acid, 33 with chloracetic esters, 33 with 3-chloropropionic acid, 33 with dimethylaminoethylchloride, 35 with ethylene oxide, 34, 38 with ethyl iodide, 33 with phenethyl chloride, 35 with 2-propynyl bromide. 32 in aprotic solvents, 35 of azothiazoles, 105... 

Condensation, of paraldehyde with diethyl malonate, 32, 54 of a-phenethyl chloride with diphenylacetonitrile, 39, 74 of phenylacetylene with ethyl orthoformate, 39, 59 of 1-phenylbiguanide with ethyl chloroacetate, 38,1 of potassium diphenylacetonitrile with benzyl chloride, 39, 73 of potassium trithiocarbonate with potassium chloroacetate, 39, 77 of sodium acetylacetonate to tetraacetylethane, 39, 61 of sodium formylacetone with cyano-acetamide, 32,32 of tetracyanoethylene with N,N-dimethylaniline, 39, 68 of thiophene, paraldehyde, and hydrogen chloride, 38, 86 of thiourea with furfuryl alcohol, 35,66... 

Equation 16 illustrates a celebrated example where ring closure competes with vicinal hydride shift (a common form of atom transfer in cations, which does not take place in free radicals or anions). The gas phase reaction was explored by preparing the dimethylfluoronium ion, (CH3)2F" , by y-radiolysis of fluoromethane. Exothermic methylation of a sample of C-yd-phenethyl chloride (where the asterisk in equation 16 symbolizes the labeled position) in the gas mixture gives a vibrationally excited ion that loses chloromethane to form two isomeric ions, a-phenethyl cation and spirooctadienyl cation (sometimes called ethylenebenzenium). Nucleophilic attack by methanol in the reaction mixture yields PhCH(CH3)OCH3, whose isotopic label remains almost entirely at the methyl group. The recovered PhCH2CH20CH3 contains equally distributed between the two methylene positions. The spirooctadienyl ion does not isomerize to a-phenethyl cation, even though DFT calculations predict the latter to be 55 kJ/mol more stable. 

N-(4-Piperidyl) propioanilide is prepared by the condensation of propionyl chloride with N-(4-piperidyl)-aniline. The resulting product is further condensed with phenethyl chloride to obtain the corresponding fentanyl base which on reaction with an equimolar portion of citric acid gives rise to the (1 1) citrate. 

Biel (3) has synthesized phenelzine by reacting hydrazine hydrate and phenethyl bromide under reflux for 7 hours. A yield of 77% was obtained. Sacha and Malasnicki (4) condensed phenethyl chloride with hydrazine under reflux in anhydrous ethanol in a nitrogen atmosphere for 12 hours. 

Barger (80) starting from phenethyl alcohol, obtained phenethyl chloride, which, when heated with dimethylamine, yielded dimethyl-phenethylamine. By nitration, reduction, diazotization, etc. a base identical with natural hordenine was obtained. Rosenmund (81) condensed p-methoxybenzaldehyde with nitromethane and reduced the alkoxy nitrostyrene to p-methoxyphenethylamine. With methyliodide a mixture of bases was formed from which, after demethylation with boiling hydroiodic acid, hordenine was obtained in low yield. Voswinckel... 

Dimethylaminoethylamino)pyridine reacts with 1-phenethyl chloride in the presence of sodamide to give A -(l-phenethyl)-A -(2-pyridyl)-A, A -dimethyl-aminoethylene diamine (IX-SO) other aryl derivatives have been prepared (see Table IX-36). 

Under similar conditions, acetophenone did not furnish any reduction product upon workup with triethanolamine. Instead, a-phenethyl chloride was obtained in 10% ee. ... 

A similar sequence begins on the even cheaper level of chlorobenzene [891], which is alkylated with tert.-butyl chloride in the presence of ferric chloride. Radical chlorination with sulfuryl chloride gives the 4-chloro-substituted 2-phenethyl chloride. 

Another polymerization technique is cationic polymerization. For example, styrene can be polymerized by treatment with a small amount of 1-phenethyl chloride, tin tetrachloride, and tetra-n-butylammonium chloride [2]. Presumably, the mechanism is as follows. 

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