Alkyl halides acids + alkenes

N,N,N, N -tetramethyl-l,8,-naph-thalenediamiDe M.P. 51 C. A remarkably strong mono-acidic base (pKg 12-3) which is almost completely non-nucleophilic and valuable for promoting organic elimination reactions (e.g. of alkyl halides to alkenes) without substitution. 

We have seen this situation before m the reaction of alcohols with hydrogen halides (8ection 4 11) m the acid catalyzed dehydration of alcohols (8ection 5 12) and m the conversion of alkyl halides to alkenes by the El mechanism (8ection 5 17) As m these other reactions an electronic effect specifically the stabilization of the carbocation intermediate by alkyl substituents is the decisive factor The more stable the carbo cation the faster it is formed... 

Problem 6.27 Why are dry gaseous hydrogen halides (HX) acids and not their aqueous solutions used to prepare alkyl halides from alkenes ... 

This Lewis acid-catalyzed electrophilic aromatic substitution allows the synthesis of alkylated products via the reaction of arenes with alkyl halides or alkenes. Since alkyl substituents activate the arene substrate, polyalkylation may occur. A valuable, two-step alternative is Friedel-Crafts Acylation followed by a carbonyl reduction. 

The first two steps of this mechanism are the same as the elimination reaction. Both reactions are carried out under acidic conditions. The difference is that halide ion serve as good nucleophiles and are present in high concentration. The elimination reaction is carried out using concentrated sulphuric acid and only weak nucleophiles are present (i.e. water) in low concentration. Thus, some elimination may occur and although the reaction of alcohols with HX produces mainly alkyl halide, some alkene byproduct is usually present. 

Scheme 10 Chem selectivity control in Lewis acid promoted reactions of alkyl halides with alkenes.

Scheme 12 Yields of 1 1 products from Lewis acid-catalyzed reactions of alkyl halides with alkenes. (R-Jf + C=C-------- R——X). (Reprinted with per-...

Scheme 7. Figure 19 finally provides the quantitative basis for the qualitative model (Scheme 11), which has been employed for deriving conditions that allow the selective synthesis of 1 1 products by Lewis acid induced reactions of alkyl halides with alkenes. 

The rearrangement processes, which can easily be studied in Lewis acid-catalyzed additions of alkyl halides to alkenes (Section III.B.2), give information about possible rearrangements in a growing chain produced from the corresponding monomer. 

The electrophile (E in -146) can be an alkyl halide, acid chloride, conjugated carbonyl compound and so on. A simple example illustrating the use of a functionalised alkyl halide, produces the Z-alkene 148 as the larger group is added by carbocupration.36 Addition in the reverse order would have given -148. 

Alkyl halide Base Alkene Conjugate acid of base Halide... 

Alkylation or acylation of aromatic compounds by means of alkyl halides, alcohols, alkenes, acyl halides, acids in the presence of Lewis acids (see 1st edition). 

The tributyltin hydride-mediated carbon-carbon bond formation via radical addition and cyclization of alkyl halides with alkenes has often been a choice for construction of various organic molecules [1], However, the requirement for high-temperature initiators or photo initiation and the difficulties associated with purification of the products from tributyltin halides tend to limit the widespread use of these methods, despite the efforts to make the methods easier [Ic, 2], Recently, nickel-mediated radical additions and cyclizations have been introduced as promising alternatives to the tributyltin hydride methods. These are the nickel powder-acetic acid method for cyclization of haloamides to y-lactams, y -lactams and in-dolones, the borohydride exchange resin-nickel boride method for radical addition, nickel-catalyzed electroreductive cyclization and nickel-catalyzed Kharasch addition of polyhalo compounds. 

However, the reaetions with secondary and tertiary alkyl halides yield alkenes, because the elimination reaction is preferred over a substitution. In contrast to the previously mentioned elimination of water from alcohol initiated by a strong acid, the elimination of hydrogen halide requires a strong base (in this case sodium ethoxide). 

Figure 7. Yields of 1 1 Products from Lewis Acid Catalyzed Reactions of Alkyl Halides with Alkenes (RX R-6-6-X). ...

Ketones are selectively reduced to alcohols using Ph2SbH and AlClg esters, acid chlorides, alkyl halides or alkenes are unaffected. 

In eontrast, dialkylhalonium salts sueh as dimethylbromonium and dimethyliodonium fluoroantimonate, whieh we prepared from excess alkyl halides with antimony pentafluoride or fluoroantimonie acid and isolated as stable salts (the less-stable chloronium salts were obtained only in solution), are very effective alkylating agents for heteroatom eompounds (Nu = R2O, R2S, R3N, R3P, ete.) and for C-alkylation (arenes, alkenes). 

We now have a new problem Where does the necessary alkene come from Alkenes are prepared from alcohols by acid catalyzed dehydration (Section 5 9) or from alkyl halides by dehydrohalogenation (Section 5 14) Because our designated starting material is tert butyl alcohol we can combine its dehydration with bromohydrm formation to give the correct sequence of steps... 

The Friedel-Crafts reaction is a very important method for introducing alkyl substituents on an aromatic ring. It involves generation of a carbocation or related electrophilic species. The most common method of generating these electrophiles involves reaction between an alkyl halide and a Lewis acid. The usual Friedel-Crafts catalyst for preparative work is AICI3, but other Lewis acids such as SbFj, TiC, SnCl4, and BF3 can also promote reaction. Alternative routes to alkylating ecies include protonation of alcohols and alkenes. 

The synthesis of an alkylated aromatic compound 3 by reaction of an aromatic substrate 1 with an alkyl halide 2, catalyzed by a Lewis acid, is called the Friedel-Crafts alkylation This method is closely related to the Friedel-Crafts acylation. Instead of the alkyl halide, an alcohol or alkene can be used as reactant for the aromatic substrate under Friedel-Crafts conditions. The general principle is the intermediate formation of a carbenium ion species, which is capable of reacting as the electrophile in an electrophilic aromatic substitution reaction. 

Alcohols undergo many reactions and can be converted into many other functional groups. They can be dehydrated to give alkenes by treatment with POCI3 and can be transformed into alkyl halides by treatment with PBr3 or SOCU- Furthermore, alcohols are weakly acidic (p/C, — 16-18) and react with strong bases and with alkali metals to form alkoxide anions, which are used frequently in organic synthesis. 

Many of the reactions of amines are familiar from past chapters. Thus, amines react with alkyl halides in S 2 reactions and with acid chlorides in nucleophilic acyl substitution reactions. Amines also undergo E2 elimination to yield alkenes if they are first qualernized by treatment with iodomethane and then heated with silver oxide, a process called the Hofmann elimination. 

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