Alkyl halides substitution reactions

Table 10.6 Summary of the Reactivity of Alkyl Halides Substitution Reactions in Nucleophilic...

Alkenes are prepared by P elimination of alcohols and alkyl halides These reactions are summarized with examples m Table 5 2 In both cases p elimination proceeds m the direction that yields the more highly substituted double bond (Zaitsev s rule)... 

Two kinds of starting materials have been examined in nucleophilic substitution reactions to this point. In Chapter 4 we saw that alcohols can be converted to alkyl halides by reaction with hydrogen halides and pointed out that this process is a nucleophilic substitution taking place on the protonated fonm of the alcohol, with water serving as the... 

Section 23.4 Aiyl halides aie less reactive than alkyl halides in reactions in which C—X bond breaking is rate-detennining, especially in nucleophilic substitution reactions. 

Structurally simple alJkyl halides can sometimes be prepared by reaction of an alkane with Cl2 or Br2 through a radical chain-reaction pathway (Section 5.3). Although inert to most reagents, alkanes react readily with Cl2 or Br2 in the presence of light to give alkyl halide substitution products. The reaction occurs by the radical mechanism shown in Figure 10.1 for chlorination. 

Radicals for addition reactions can be generated by halogen atom abstraction by stannyl radicals. The chain mechanism for alkylation of alkyl halides by reaction with a substituted alkene is outlined below. There are three reactions in the propagation cycle of this chain mechanism addition, hydrogen atom abstraction, and halogen atom transfer. 

In conversion of alcohols to alkyl halides (substitution), very often, the reaction is accompanied by the formation of some alkenes (elimination). 

Some organic reactions can be accomplished by using two-layer systems in which phase-transfer catalysts play an important role (34). The phase-transfer reaction proceeds via ion pairs, and asymmetric induction is expected to emerge when chiral quaternary ammonium salts are used. The ion-pair interaction, however, is usually not strong enough to control the absolute stereochemistry of the reaction (35). Numerous trials have resulted in low or only moderate stereoselectivity, probably because of the loose orientation of the ion-paired intermediates or transition states. These reactions include, but are not limited to, carbene addition to alkenes, reaction of sulfur ylides and aldehydes, nucleophilic substitution of secondary alkyl halides, Darzens reaction, chlorination... 

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... 

Carbonium ions can be generated at a variety of oxidation levels. The alkyl carbocation can be generated from alkyl halides by reaction with a Lewis acid (RCl + AICI3) or by protonation of alcohols or alkenes. The reaction of an alkyl halide and aluminium trichloride with an aromatic ring is known as the Friedel-Crafts alkylation. The order of stability of a carbocation is tertiary > secondary > primary. Since many alkylation processes are slower than rearrangements, a secondary or tertiary carbocation may be formed before aromatic substitution occurs. Alkylation of benzene with 1-chloropropane in the presence of aluminium trichloride at 35 °C for 5 hours gave a 2 3 mixture of n- and isopropylbenzene (Scheme 4.5). Since the alkylbenzenes such as toluene and the xylenes (dimethylbenzenes) are more electron rich than benzene itself, it is difficult to prevent polysubsiitution and consequently mixtures of polyalkylated benzenes may be obtained. On the other hand, nitro compounds are sufficiently deactivated for the reaction to be unsuccessful. 

The remainder of Chapter 7 is devoted to a discussion of the substitution reactions of alkyl halides. Elimination reactions are discussed in Chapter 8. 

Nitro Substitution Products.—Nitric acid is HO—NO2 and nitrous acid is HO—NO. If these are reduced ammonia is the result. When the silver salt of nitrous acid acts upon an alkyl halide a reaction occurs similar to that of potassium cyanide upon the alkyl halides. 

Reaction of sodium acetylides with alkyl halides. Substitution vs, elimination... 

Alkyl sulfonates offer a very real advantage over alkyl halides in reactions where stereochemistry is important this advantage lies, not in the reactions of alkyl sulfonates, but in their preparation. Whether we use an alkyl halide or sulfonate, and whether we let it undergo substitution or elimination, our starting point for the study is almost certainly the alcohol. The sulfonate must be prepared from 4he alcohol the halide nearly always will be. It is at the alcohol stage that any resolution will be carried out, or any diastereomers separated the alcohol is then converted into the halide or sulfonate, the reaction we are studying is carried out, and the products are examined. 

Alkylation involves treating ammonia or an amine with an alkyl halide. The amine, as a Lewis base with a non-bonding electron pair, is a good nucleophile and displaces the halide ion from the alkyl halide the reaction is nucleophilic substitution with a neutral nucleophile. SN2 reactions are common. Since alkylation tends to continue until four groups are bonded to the nitrogen, it has limited synthetic utility. 

Section 4.11 The conversion of an alcohol to an alkyl halide on reaction with a hydrogen halide is a nucleophilic substitution. Nucleophilic substitutions (Sn) are classihed as S l or 8 2 according to whether the rate-determining step is unimolecular or bimolecular. 

Many substitution and addition reactions have been carried out on the solid phase as these reactions are ideally suited for the introduction of commercially available building blocks such as amines and alkyl halides. The reaction conditions, however, are often incompatible with other functionalities in the molecule. An alternative reaction carried out under neutral conditions is the Mitsunobu reaction. A variety of Mitsunobu reactions have been carried out on the solid support, where work-up is much more straightforward than the analogous solution-phase reaction. 

Primary alkyl halides cannot undergo S l or El reactions Secondary alkyl halides substitution and elimination Tertiary alkyl halides substitution and elimination... 

Lewis acid AICI3, BF3, HF, etc. RX may be an alkyl halide, substituted alkyl halide, alkene or alcohol. The Lewis acid functions to generate the electrophile that attacks the ring. Since the n-propyl group is activating, the reaction should occur with orientation ortho and para. 

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