Alkyl halides substitution and

Mechanism 6-1 Allylic Bromination 228 Summary Methods for Preparing Alkyl Halides 229 6-7 Reactions of Alkyl Halides Substitution and Elimination 231 6-8 Second-Order Nucleophilic Substitution The Sn2 Reaction 232 Key Mechanism 6-2 The S j2 Reaction 233 6-9 Generality of the SN2 Reaction 234... 

Primary alkyl halides primarily substitution Secondary alkyl halides substitution and elimination Tertiary alkyl halides only elimination... 

Trialkylstannyl-lithium reacts with secondary alkyl halides (substitution) and with a/S-unsaturated carbonyl compounds (conjugate addition) to give alkyl tin derivatives which may be oxidized with chromic anhydride in pyridine to give a saturated ketone. Applying the procedure to a cycloalkenone, an efficient dialkyl-ative enone transposition can be realized (Scheme 68). ... 

The iron complex 16 in anhyd benzene was treated with an alkyl halide (excess) and anhyd NaHC03 (1 mol equiv) and the mixture was stirred at 20 "C for 20 h. For acylation, an acyl chloride (1 mol equiv) and anhyd NaHCO, were employed and the mixture was stirred at 20CC for 1-2 h. For decomplexation, the TV-substituted iron complex 17 and a 20-fold molar excess of freshly sublimed Me3NO in acetone were stirred for 20 h at 20 C and the reaction mixture was worked up by chromatography to give 18. 

The C-H bond in CBnHi2 and related anions can be metallated by butyllithium and then converted into C-substituted anions with aldehydes, alkyl halides, Ph3SiCl, and Ph2PCl.322-329 C-halogenated (F,Cl,Br, or I) derivatives are made from the C-copper derivative with (PhS02)2NF or the corresponding N-halosuccinimide.330 The l-Me-2,3>4,5,6,7,8,9,10,ll>12-Fu-CBii- anion is made from the reaction of the corresponding Fn anion with... 

A chemical reaction Is the result of competition It Is a race that Is won by the fastest runner. A collection of molecules tend to do, by and large, what Is easiest for them. An alkyl halide with p-hydrogen atoms when reacted with a base or a nucleophile has two competing routes substitution (Sj,jl and Sj,j2) and elimination. Which route will be taken up depends upon the nature of alkyl halide, strength and size of base/nucleophile and reaction conditions. Thus, a bulkier nucleophile will prefer to act as a base and abstracts a proton rather than approach a tetravalent carbon atom (steric reasons) and vice versa. 

A nucleophile is an electron rich species that reacts with an electrophile. The term electrophile literally means electron-loving , and is an electron-deficient species that can accept an electron pair. A number of nucleophilic substitution reactions can occur with alkyl halides, alcohols and epoxides. However, it can also take place with carboxylic acid derivatives, and is called nucleophilic acyl substitution. 

Sometimes it is convenient to synthesise an activated alcohol that can be used in nucleophic substitution reactions like an alkyl halide. Mesylates and tosylates are such sulphonate compounds which serve this purpose. They can be synthesised by action of alcohols with sulphoxyl chlorides in the presence of a base like pyridine or triethylamine (Following fig.). The base serves to mop up the HC1 that is formed and avoids acid-catalysed rearrangement reactions. 

Under these conditions, the order of reactivity to nucleophilic substitution changes dramatically from that observed in the Sn2 reaction, such that tertiary alkyl halides are more reactive then secondary alkyl halides, with primary alkyl halides not reacting at all. Thus a different mechanism must be involved. For example, consider the reaction of 2-iodo-2-methylpropane with water. (Following fig.). In it, the rate of reaction depends on the concentration of the alkyl halide alone and the concentration of the attacking nucleophile has no effect. Thus, the nucleophile must present if the reaction is to occur, but it does not matter whether there is one equivalent of the nucleophile or an excess. Since the reaction rate depends only on the alkyl halide, the mechanism is called the SN1 reaction, where SN stands for substitution nucleophilic and the 1 shows that the reaction is first order or unimolecular, i.e. only one of the reactants affects the reaction rate. 

TABLE 3. Some calculated energy barriers (A/A in kJ mol-1) for homolytic substitution by some silyl radicals at the halogen atom in some alkyl halides (RX), and the chalcogen atom in some alkylchalcogenols (REH) (equations 12 and 13)... 

With less hindered alkyl halides hydroxide would not be a good choice as a base for an elimination because it is rather small and still very good at Sn2 substitutions (and even with tertiary alkyl halides, substitution outpaces elimination at low concentrations of hydroxide). So what are good alternatives ... 

Tlie reactivities of the substrate and the nucleophilic reagent change yhen fluorine atoms are introduced into their structures This perturbation becomes more impor tant when the number of atoms of this element increases A striking example is the reactivity of alkyl halides Sfjl and Sn2 mechanisms operate when few fluorine atoms are incorporated in the aliphatic chain, but perfluoroalkyl halides are usually resistant to these classical processes However, formal substitution at carbon can arise from other mecharasms For example nucleophilic attack at chlorine, bromine, or iodine (halogenophilic reaction, occurring either by a direct electron-pair transfer or by two successive one-electron transfers) gives carbanions These intermediates can then decompose to carbenes or olefins, which react further see equations 15 and 47) Single-electron transfer (SET) from the nucleophile to the halide can produce intermediate radicals that react by an SrnI process see equation 57) When these chain mechanisms can occur, they allow reactions that were previously unknown Perfluoroalkylation, which used to be very rare, can now be accomplished by new methods see for example equations 48-56, 65-70, 79, 107-108, 110, 113-135, 138-141, and 145-146)... 

The elimination reactions of alkyl halides, alcohols and quaternary ammonium salts to form alkenes compete with substitution reactions. 

---