Alkylation with isopropyl chloride

Friedel-Crafts alkylation of benzo[6]thiophene has received little attention. The published results, which deserve reexamination, indicate that exclusive 3-substitution occurs in some cases, whereas in others, 2-substitution predominates. Benzo[6]thiophene is alkylated with isopropyl chloride, isopropanol, or propene in the presence of various acid catalysts under a variety of reaction conditions to give a mixture of 2- and 3-isopropylbenzo[6]thiophene in which the 2-isomer predominates (78-92%).358 410 In contrast, alkylation with isobutene in the presence of either 80% sulfuric acid415 or 100% phosphoric acid416 is said to afford exclusively 3-/er<-butylbenzo[6]thiophene in yields of 100 and 75%, respectively. In neither case was the structure of the product rigorously confirmed. Likewise, 3-Jeri-amylbenzo [63-thiophene is the exclusive product of alkylation with tert-amyl alcohol in the presence of stannic chloride414 alkylation with pent-l-ene, hex-l-ene, and a Ci8 propylene polymer is also claimed to give... 

Mechanism. The mechanism of alkylation and of other related Friedel-Crafts reactions is best explained by the carbocation concept. The alkylation of benzene with isopropyl chloride may be used as a general example ... 

Schiff s base (j ) derived by reaction of p-chloro-anil ine and borohydride followed by acylation with phenylacetyl chloride produces amide 22,. Selective hydrolysis with HBr followed by alkylation with isopropyl bromide completes the synthesis of lorcainide (20). ... 

Similarly, benzo[6]thiophene also yields mixtures of 2- and 3-alkyl derivatives on alkylation with alkenes or alkanols in the presence of acids <70AHC(11)177). Thus with isopropyl chloride, isopropanol or propene, mixtures of 2- and 3-isopropyl derivatives are formed. Alkylation by 2-methylpropene in the presence of PPA gives 2-7-butyl- (22%) and 3-7-butyl-(71%) benzo[6]thiophenes with 7-butanol and cone. H2S04, the yields are 2-7-butyl (6%) and 3-7-butyl (89%) (72JCS(Pl)414). 

A study48 of the direct upper-rim alkylation of calix[n]arenes has shown that, with n = 8, reaction with isopropyl chloride in 1,2-dichloroethane with AICI3 gives isopropylation, whereas when n = 4 hydroxyisopropylation is observed. With n = 6 there is a mixture of products, indicating overall an increase in phenolic behaviour as n increases from 4 to 8. 

Satisfactory results were obtained in the Nafion-H-catalyzed gas-phase alkylation of aromatic hydrocarbons with alkyl halides235 [Eq. (5.88)]. Alkylhalides are reactive Friedel-Crafts alkylating agents and give high conversions when alkylating benzene in the gas phase over Nafion-H catalyst. For example, in the alkylation of benzene with isopropyl chloride, conversions as high as 87% were achieved (Table 5.17, run 11). Conversions, however, were temperature and contact time dependent (Table 5.17). 

The results obtained in the gas-phase isopropylation of various aromatic hydrocarbons with isopropyl chloride over Nafion-H catalyst showed only a relatively small variation of reactivity in going from fluorobenzene to xylenes.235 Therefore, it has been assumed that the reaction rate is controlled by the formation of a reactive electrophilic intermediate (possibly, protonated alkyl halide 61, or some form of incipient alkyl cation) rather than by cr-complex formation between the electrophile and the aromatic nucleus [Eq. (5.89)]. 

This procedure illustrates a process which is general for 1,1-diphenyl substituted hydrocarbons. Diphenylmethane has been alkylated with benzyl chloride, benzhydryl chloride, a-phenyl-ethyl chloride, /3-phenylethyl chloride, isopropyl chloride, 2-ethylbutyl bromide, and n-octyl bromide in yields of 99, 96, 97, 88, 86, 96, and 99%, respectively. 

AICI3-catalyzed alkylation of calix[8]arenes with isopropyl chloride gives selective upper-rim isopropylation, showing the phenolic nature of the calixarenes (equation 7). The reaction is limited to calix[8]arenes and is not successful with calix[4]arenes and calix[6]arenes, in which case mixtures of products are obtained. 

Simple alkyl chlorides decompose smoothly over a suitable catalyst to an equilibrium mixture of olefinic hydrocarbon and hydrogen chloride for instance, isobutene in equilibrium with t-butyl chloride [33], propylene with isopropyl chloride and ethylene with ethyl chloride [34]. Catalysts were glass wool and a mixture of nickel, cobalt and cadmium chlorides. When a metal is substituted for the chloride catalyst and the equilibrium is disturbed by removal of the olefin, the net result observed is reaction of the HCl with the metal. Mould, Silver and Syrett [35] heated solutions of organochlorine compounds for 6 hours at 473 K in the presence of steel filings which were then washed free of oil and analyzed for inorganic chloride the reactivities thus found are shown in Table 11-9. The order of reactivity is what an organic chemist would expect from reactions involving the elimination of HCl. The thermodynami-... 

Similarly, reaction of chlorobenzene with isopropyl chloride imder Friedel—Crafts conditions produced primarily the ortho and para alkylation products after a short reaction period. Allowing the reaction mixture to stand for a week before workup, however, produced primarily the meta product. In both of these cases, the product isolated after a short time is said to be the product of kinetic control of the product distribution, since the product isolated is the one that is formed faster. The product isolated after a longer time is said to be the product of thermodynamic control of product distribution, since it is the more stable product. ... 

C-Alkylations may be discussed under the headings of alkene reactions and A/-alkyl rearrangements. The isopropylation of benzene and naphthalene are two important examples of alkylation with alkenes (see Alkylation). Manufacture of j butylaniline, by heating /V-butylaniline with 2inc chloride, typifies the rearrangement reaction appropriate to and higher alkyl derivatives. 

Schrauzer and co-workers have studied the kinetics of alkylation of Co(I) complexes by organic halides (RX) and have examined the effect of changing R, X, the equatorial, and axial ligands 148, 147). Some of their rate constants are given in Table II. They show that the rates vary with X in the order Cl < Br < I and with R in the order methyl > other primary alkyls > secondary alkyls. Moreover, the rate can be enhanced by substituents such as Ph, CN, and OMe. tert-Butyl chloride will also react slowly with [Co (DMG)2py] to give isobutylene and the Co(II) complex, presumably via the intermediate formation of the unstable (ert-butyl complex. In the case of Co(I) cobalamin, the Co(II) complex is formed in the reaction with isopropyl iodide as well as tert-butyl chloride. Solvent has only a slight effect on the rate, e.g., the rate of reaction of Co(I) cobalamin... 

Reduction of simple alkyl halides to alkanes by ethylenediamine complexes of Cr(II), denoted Cr"(en) occurs readily , e.g. for isopropyl chloride in aqueous dimethylformamide at 25 °C simple second-order behaviour is found with ki dependent on [en]/[Cr(II)] but reaching a limiting value of 1.6x 10 l.mole . sec . Competition studies between a mixture of two alkyl chlorides for Cr(II) was achieved by estimating alkane products by gas-liquid chromatography and... 

Mg+" reacts with alkyl halides in the gas phase via a range of substrate-dependent pathways Not all halides are reactive—examples of unreactive substrates include methyl chloride, vinyl chloride, trichloro and tetrachloro ethylene. Reaction with ethyl chloride proceeds via an elimination reaction (equation 18) followed by a displacement reaction (equation 19). For larger alkyl halides, such as isopropyl chloride, chloride abstraction also occurs (equation 20). For multiply halogenated substrates such as carbon tetrachloride, oxidative reactions occur (equations 21 and 22), although organometallic... 

Silica gel is an effective catalyst for the t-butylation of thiophene and benzo[/ ]thiophene using t-butyl bromide. 2,5-Di-r-butylthiophene and 3-f-butylbenzo[b]thiophene can be prepared easily by this procedure (84JOC4161). Alkylation of thiophene with f-butyl chloride, isopropyl chloride or ethyl chloride at - 70°C in the presence of A1C13 produced a-complexes under kinetic control. On thermal equilibration, migration of alkyl from position 3 to position 2, as well as disproportionation to dialkyl-and trialkyl thiophenes can occur (86T759). 

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