Chapter 10 1
How alkyl halides react δ+ δ- RCH 2 -X X= halogen X = higher EN C = lower EN This polar carbon-halogen bond causes alkyl halide to undergo S N and elimination reaction. 2
The mechanism of S N 2 reaction CH 3 Br + OH - CH 3 OH + Br - Rate α [alkyl halide][nucleophile] Rate = k[alkyl halide][nucleophile] S N 2 reaction S stands for substitution N stands for nucleophilic 2 stands for bimolecular 3
Relative rates of SN2 reaction (Table 10.1) R-Br + Cl - S N 2 R-Cl + Br - Structure Type Relative rate CH 3 Br Methyl radical 1200 CH 3 CH 2 Br 1º radical 40 CH 3 CH 2 CH 2 Br 1º radical 16 2º radical 1 3º radical Too low to measure 4
Mechanism of the S N 2 reaction Reaction take place in a single step 5
Effect of bulkiness More bulkiness of alkyl halide, harder for nucleophile to attack carbon (see Table 10.1 and Fig 10.1), lower rate. Steric Effect Steric effect that decreases reactivity is called steric hindrance Relative reactivities of alkyl halide in an S N 2 reaction Methyl halide > 1º > 2º > 3º (most reactive) (least reactive) (less steric) (most steric) 6
Coordinate diagram (Fig 10.2) Methyl halide 2º alkyl halide 7
Fig 10.3: after substitution occur, carbon has inverted its configuration (like an umbrella) Example (R)-2-bromobutane (S)-2-bromobutanol Configuration is inverted 8
Example Configuration is inverted 9
Factor affecting S N 2 reactions 1. The leaving group 2. The nucleophile 1. The leaving group Relative rates of alkyl halides in the S N 2 reaction RI > RBr > RCl > RF (most reactive) (least reactive) the weaker the basicity of a group, the better is its leaving ability 10
2. The nucleophile Basicity -A measure how well a compound (a base) share its lone pair electron with a proton -The better it shares, the stronger base 11
Nucleophilicity is a measure of how readily a compound (a nucleophile) is able to attack an electron-deficiency atom In general, stronger bases are better nucleophiles A specie with negative charges is a stronger base and better nucleophile. 12
Better nucleophile OH - CH 3 O - NH 2 - Poorer nucleophile H 2 O CH 3 OH NH 3 13
Relative acid strength NH 3 < H 2 O < HF (Element in upper row has higher EN) Relative base strength NH 2 - < OH - < F - 14
The mechanism of S N 1 reaction Rate = k[alkyl halide] 15
Table 10.2 relative rates of S N 1 reaction (with H 2 O) Structure Type Relative rate 3º alkyl halide 1,200,000 2º alkyl halide 11.6 CH 3 CH 2 Br 1º alkyl halide ~1 CH 3 Br methyl ~1 16
Explain table 10.2 with this as follow. 3º alkyl halide > 2º > 1º (most reactive) (least reactive) (most stable) (least stable) 17
Configuration of product from SN1 Enantiomers are obtained. Nucleophile can attack in 2 possible ways. 18
Example: cyclic 19
Factors affecting S N 1 reactions 1. The leaving group 2. The nucleophile 1. The leaving group Relative reactivities of alkyl halides in the S N 1 reaction RI > RBr > RCl > RF (most reactive) (least reactive) 2. The nucleophile The nucleophile involve after the rate-determining step, so the nucleophile has no effect on the rate of S N 1 reaction. 20
Comparison of the S N 2 and S N 1 reactions (Table 10.3) S N 2 S N 1 1 step mechanism 2 step mechanism A bimolecular rate determining step A unimolecular rate determining step Product has inverted configuration Reactivities methyl>1º>2º>3º Products have both retained and inverted configuration Reactivities 3º>2º>1º>methyl 21
Elimination reactions of alkyl halide substitution CH 3 CH 2 CH 2 X + Y - CH 3 CH 2 CH 2 Y + X - Rate = k[alkyl halide][base] elimination CH 3 CH=CH 2 + HY + X - Mechanism of E2 reaction -1 step reaction -π bond is formed 22
The E1 reaction Rate = k[alkyl halide] Mechanism of the E1 reaction 23
Relative reactivities of alkyl halides in E2 and E1 reaction RI > RBr > RCl > RF (most reactive) (least reactive) 24
Products of Elimination Reactions - Hydrogen is removed from β-carbon - In this case, 2 atoms of β-carbon are same. - Only one product is obtained. 25
Example: -In this case, 2 products are obtained. 80% 20% 2-butene 1-butene 26
Reaction coordinate diagram for E2 reaction -The major product of an E2 reaction is the most stable alkene -The greater the number of substituents, the more stable is the alkene 27
Relative reactivities of alkyl halides in an E2 reaction 3º alkyl halide > 2º > 1º 3 substituents 2 substituents 1 substituent Reactivities of alkyl halides in an E1 reaction 3º alkyl halide > 2º > 1º 28
Comparison of cis- and trans- products from elimination reaction (E)-2-butene More stable Major product (Z)-2-butene less stable (steric effect) minor product 29
Competition between S N 2/E2 and S N 1/E1 Consider 2 factors 1. The concentration of the nucleophile/base 2. The reactivity of the nucleophile/base S N 1 S N 2 Rate = k 1 [alkyl halide] + k 2 [alkyl halide][nucleophile] + k 3 [alkyl halide] + k 4 [alkyl halide][base] E1 E2 30
1. The concentration When [nucleophile] increase, rate of S N 2, E2 increase But rate of S N 1, E1 is not changed. 2. The reactivity When reactivity of nuclephile increase, rate of S N 2, E2 increase but rate of SN1, E1 is not changed. Therefore S N 2, E2 reactions are favored by a high concentration of a good nucleophile/strong base S N 1, E1 reactions are favored by a poor nucleophile/weak base, because poor nucleophile/weak base disfavors S N 2 and E2 reaction. 31
Competition between substitution and elimination The relative amount of S N and elimination products depend on whether the alkyl halide is 1º, 2º, or 3º S N 2, E2 conditions 32
Table10.4 relative reactivities of alkyl halides S N 2 1º>2º>3º S N 1 3º>2º>1º E2 3º>2º>1º E1 3º>2º>1º 33
S N 1, E1 conditions From Table10.4 1º alkyl halide can undergo S N 2 only 2º alkyl halide can undergo S N 2, S N 1, E2, E1 3º alkyl halide can undergo S N 1, E2, E1 Table 10.6 stereochemistry of S N and Elimination reaction S N 1 products can be both R and S E1 products can be both E and Z (major is E) S N 2 products can be only inverted product E2 products can be both E and Z (major is E) 34