ALKYL HALIDES Predict SN1 and SN2 This is SN1 reaction because the substrate is secondary and benzylic, the nucleophile is weakly basic, and the solvent is protic. (b) This is SN2 reaction because the substrate is primary, the nucleophile is a reasonably good one, and the solvent is polar aprotic.

SNi Mechanism Aliphatic Nucleophilic substitution reaction leading to retention of configuration (Internal Nucleophilic substations). The displacement of -OH by Cl- using thionyl chloride. This substitution proceeds through SNi Mechanism, in which there is retention of configuration. The reaction follows Second order kinetic Rate α [R3C-OH] [SOCl2]

Neighboring group Participation (NGP) In first step of the reaction the neighboring group acts as nucleophile pushing out the leaving group. In the 2nd step external nucleophile pushing out the neighboring group.

Neighboring group Participation (NGP The first step is the conversion of the OH to the corresponding alkoxide. This ion (alkoxide) act as nucleophile. It attacks the carbon carrying chlorine from the back side. This is an internal SN2 reaction and I result in the inversion of configuration. A classic example of NGP is the reaction of a sulfur or nitrogen mustard or (halide) with a nucleophile, the rate of reaction is much higher for the sulfur mustard and a nucleophile than it would be for a primary alkyl chloride without a heteroatom.

Substitution and Elimination Two kinds of reactions can take place when a nucleophile /Lewis base reacts with an alkyl halide. The nucleophile can either substitute for the halide by reaction at carbon or can cause elimination of HX by reaction at a neighboring hydrogen. Elimination reactions are more complex than substitution reactions. Elimination reactions almost always give mixtures of alkene products, and we can usually predict which will be the major product.

Substitution and Elimination

Dehydrohalogenation Elimination That is, dehydrohalogenation reaction when alkyl halide is heated with a strong base using a relative non-polar solvent.

Elimination: Dehydrohalogenation (cont.)   Note that both base and nucleophile are electron rich species, hence both elimination and nucleophilic reaction would occur at the same time unless the reaction conditions are carefully chosen. Normally, elimination reaction occurs at high temperature, alcoholic medium (relatively non-polar) and the alkyl halide is highly branched (e.g. tertiary or secondary).

Elimination Reactions The reactions in which two groups or atoms are removed from molecule are called Elimination reaction. They result in the formation of unsaturated compounds. Elimination reactions involve the loss of elements from the starting material to form a new  bond in the product.

Classification The two leaving group’s may be removed from the two adjacent atom OR from the same carbon or On this bases elimination reaction are classified as, 1-2 OR β-Elimination The reaction in which both the groups are removed from two adjacent atoms is called β-elimination or 1-2 elimination reaction. This results in the formation of double bond. The general β-elimination reaction can be represented as

1-1 or α Elimination The reaction in which elimination of two groups occur from the same carbon. The carbon to which the leaving group is attached is called α carbon. As the elimination only occurs from α carbon. Therefore the reaction is called α elimination and a carbene is formed. carbene

E2 Mechanism In E2 Mechanism both the groups get deposit simultaneously. Thus the rate of the reaction depends on both the concentration of substrate and base.

ORIENTATION IN E2 MECHANISM There are some substrates on which more than one β carbon are available e.g. Let us consider the alkyl halide Here in this case two β carbon are available so if base induced elimination of this molecule is taken in to consideration then two kinds of olefin will be possible so in this case we consider elimination reaction to be in two modes.

Hoffman Elimination The elimination gives olefin carrying less number of alkyl groups. In this case the hydrogen is eliminated from that β carbon that carries maximum number of hydrogen atoms. Zaitsev Elimination (Zaitsev’s rule) The elimination gives olefin carrying greater number of alkyl group. In this case the hydrogen is eliminated from that β carbon that carries minimum number of hydrogen atoms.

(Zaitsev’s rule)

E1 Mechanism It is a two steps process in the first step the substrate ionizes to form carbonium ion by losing the leaving group. In the second step, the carbonium ion loses hydrogen from the β carbon to from the product.

THREE POSSIBAL REACTIONS II) III)

E1cB Mechanism We know that in E1 mechanism X leaves first and then hydrogen, In E2 mechanism X and H Leave simultaneously. There is a 3rd possibility that H leaving 1st and then X. This is called E1cB mechanism.

E1cB Mechanism Therefore in E1cB mechanism H leaves first leading to the formation of carbanion (─ ive charge). The carbanion loss X to form the end products. This reaction is therefore completed in two steps. This mechanism is called cabanion mechanism.

Ei or Pyrolytic Syn Elimination There are a number of elimination reaction in which elimination occur by heating alone or in inert solvent to yield alkenes. In Ei reaction both the atoms are eliminated from the side. Therefore they are also known as pyrolytic syn elimination.

Syn Elimination Some salient features of pyrolytic syn elimination are The elimination of both atoms takes place simultaneously with out the addition of any external reagent. Ei reaction carried out in neutral non polar solvents. The Ei reaction goes through the formation of cyclic transition state and the mechanism is a single step process i.e. concerted. These reaction are highly stereoselctive and the stereochemistry totally transferred to the product.

GRIGNARDS REAGENT R-Mg-X

GRIGNARD’S REAGENT F. A. Victor Grignard (1871-1935) was a Nobel Prize winning French chemist. In 1900, V. Grignard reported that an alkyl halide (RX) reacts with magnesium metal (Mg) in diethyl ether to give a cloudy solution of an organomagnesium compound (RMgX). He was awarded the Nobel Prize in Chemistry in 1912. The Grignard reagent is usually described with the general chemical formula R-Mg-X. Iodides, bromides, and chlorides can be used, including aryl and alkyl halides.

GRIGNARDS REAGENT The Grignard reaction became one of the most versatile C-C bond forming tools. It involves an insertion of magnesium into the new carbon–halogen bond.

GRIGNARDS REAGENT PREPARATION There is also a change in oxidation state of the magnesium, from Mg(0) to Mg(II). The reaction is therefore known as an oxidative insertion or oxidative addition.

PREPARATION GRIGNARDS REAGENT The C-Mg bond is very polar and the partial negative charge resides on the carbon atom, so Grignard reagents are excellent carbon nucleophiles.

R-Mg-X Formation (Radical Mechanism) It also involves radical intermediates. Grignard formation does not involve a radical chain mechanism. It is a non-chain radical reaction.

Ether Solvent Diethyl ether is an especially good solvent for the formation of Grignard reagents because ethers are non-acidic (aprotic). Water or alcohols would protonate and thus destroy the Grignard reagent, and would form a hydrocarbon. But Grignard reagents are stable in ethers.

Ether Solvent Ethers are good at solvating cations, because the C-O bond is relatively polar, thus allowing the oxygen end of the ether dipole to solvate and stabilize the magnesium ion.

REACTIONS OF GRIGNARD REAGENTS The Mg-C bond in a Grignard reagent is polarized, e.g. methylmagnesium bromide. The carbon attached to Mg bears a partial negative charge. This carbon is Nucleophilic, and is subject to attack by electrophiles. An Electrophile is a chemical species which seeks electrons.

GOOD LUCK