F-Alkyl chlorides

This is, in fact, an unusual way to carry out such reactions. The Friedel-Crafts alkylation, as this is known, usually involves treating benzene with a f-alkyl chloride and the Lewis acid AlC. Rather in the manner of the reaction with bromine, AICI3 removes the chlorine atom from f-BuCl and releases the f-Bu cation for the alkylation reaction. 

We have drawn the substitution at the benzylic centre as an Sn2 reaction as it would normally be with a primary alkyl halide, though it could be S>jl in this case as the benzylic cation is stable. Friedel-Crafts alkylation works well with relatively stable cations especially tertiary cations. The cation can be generated in a number of ways such as the protonation of an alkene, the acid-catalysed decomposition of a tertiary alcohol, or the Lewis-acid-catalysed decomposition of a f-alkyl chloride. 

Friedel-Crafts alkylation with f-alkyl chlorides and Lewis acids (usually AICI3) gives f-alkyl benzenes. The more reliable Friedel-Crafts acylation with acid chlorides and Lewis acids (usually AICI3) gives aryl ketones. 

Titanium(IV) is a powerful but selective Lewis acid which can promote the coupling of allylsilanes with carbonyl compounds and derivatives In the presence of titanium tetrachlonde, benzalacetone reacts with allyltnmethylsilane by 1,4-addition to give 4-PHENYL-6-HEPTEN-2-ONE. Similarly, the enol silyl ether of cyclopentanone is coupled with f-pentyl chloride using titanium tetrachlonde to give 2-(tert-PENTYL)CYCLOPENTANONE, an example of a-tert-alkylation of ketones. 

Perhydropyrido[l,2-a]pyrimidin-2-one was A -alkylated with 1,4-dibro-mobutane to yield a 1-(4-bromobutyl) derivative (94MIP6). 6-Methyl-4-oxo-4/f-],6,7,8,9,9a-hexahydro-4//-pyrido[],2-a]pyrimidine-3-carboxylate 138 was alkylated with alkyl chlorides 139 to give 1-substituted derivatives 140 (97MIP2). 

V-Aminoalkylation of 5/f-dibenzo[4/][l,3]diazcpin-6(7//)-ones 17 is accomplished by successive treatment with sodium amide and a (dialkylamino)alkyl chloride. Selected examples are given yields were not reported.179 ... 

M - 37C1 from alkyl chlorides (H20 + F) from certain fluoroalcohols... 

Tertiary alkyl halides undergo a series of reactions when treated with hydrogen fluoride. f-Amyl chloride by means of reactions catalyzed by hydrogen fluoride yielded a series of teritary chlorides including f-butyl chloride (Simons et al., 35). t-Butyl chloride gives the same series of... 

There are only few reactions known introducing substituents to the H-bearing nitrogen of oxaziridines. JV-Alkylation of l-oxa-2-azaspiro[2.5]octane (3,3-pentamethylene-oxaziridine 52) with f-butyl chloride to give (53) was carried out for structure proof of (52). This reaction is of no preparative importance, since N-alkylated oxaziridines are easily obtained by ring synthesis. 

There is direct evidence, from ir and nmr spectra, that the f-butyl cation is quantitatively formed when f-butyl chloride reacts with A1CI3 in anhydrous liquid HCI.246 In the case of olefins, Markovnikov s rule (p. 750) is followed. Carbocation formation is particularly easy from some reagents, because of the stability of the cations. Triphenylmethyl chloride247 and 1-chloroadamantane248 alkylate activated aromatic rings (e.g., phenols, amines) with no catalyst or solvent. Ions as stable as this are less reactive than other carbocations and often attack only active substrates. The tropylium ion, for example, alkylates anisole but not benzene.249 It was noted on p. 337 that relatively stable vinylic cations can be generated from certain vinylic compounds. These have been used to introduce vinylic groups into aryl substrates.250... 

The three picolines react with alkyl halides in liquid ammonia solution in the presence of sodamide to yield the corresponding monoalkylpyridines. a-Picoline also reacts with alkyl chlorides in the presence of sodamide either alone or in the presence of xylene to give a fair yield of monoalkylpyridineC5H4N.CHtR. With f-picoline under similar experimental conditions disubstitution of the alkyl group (CSH4N.CHR2) occurs to an appreciable extent. The preparation of Hie three n-amylpyridines is described the 3- and 4-compounds by the liquid ammonia - sodamide method and the 2-compound by the sodamide-xylene procedure. 

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). 

The carbon-halogen bond distances in acyl halides increase in the direction F < Cl < Br < I, and are similar, but slightly larger than, those of the alkyl halides (Table 7). Nuclear quadrupole resonance frequencies of halogen compounds suggest that the charge density on the chlorine atom of an acyl chloride is greater than that on an alkyl chloride (Table 8). 

Benzo[6]furan may be alkylated with f-butyl chloride and zinc chloride, the products being the 2- and 3-substituted compounds in the ratio 1 2. Benzo[6]furan is chloromethylated at the 2-position. 2-Methyl- and 2-phenyl-benzo[6]furan are chloromethylated in the 3-position. 

Friedel-Crafts alkylation of 2,5-dimethylthiophene with f-butyl chloride and A1C13 gave only the mono-r-butylated product (49) and none of the expected di-f-butylated thiophene (50). In order to facilitate di-r-butylation at positions 3 and 4, the substituents at 2 and 5 were tied back in the thiophenophane (51). This on alkylation gave, unexpectedly, the rearranged mono-f-butyl derivatives (52 30%) and (53 57%), and the di-f-butyl derivative (54 12%). The structures of the products were proved by NMR, Raney nickel desulfurization and independent synthesis (75T2551). One other such isomerization under Friedel-Crafts conditions had been previously reported (65JOC1058) 2,5-di-f-butylthiophene isomerizing to 2,4-di-f-butylthiophene. 

This is essentially the procedure actually followed. Alkylation was effected, however, not with te/f-butyl chloride and aluminum chloride but with 2-methylpropene and phosphoric acid. 

Solution of antimony pentafluoride in anhydrous HF was found to be an efficient medium for alkylation reactions of fluoroolefins. Compounds, known to give stable carbocations in superacidic media are excellent alkylating agents. For example, f-butyl chloride (57) reacts with TFE, giving the corresponding alkane 58 ... 

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