substitution elemination reactions

7/28/2019 Substitution Elemination Reactions

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SUBSTITUTION REACTIONS OF AL KYLHALIDES

SN1, S N2, E1 & E2 REACTIONS
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Reactions of Alkyl Halides (R-X): [SN1, SN2, E1, & E2 reactions]

The -carbon in an alkyl halide is electrophilic (electron accepting) foreither or both of two reasons

a) the C to X (F, Cl, Br) bond is polar making carbon +ve

(4.0 2.5) = 1.5

(3.0

2.5) = 0.5

(2.8 2.5) = 0.3

FH 3 C EN (F-C) =

EN (Cl-C) =

EN (Br-C) =

EN (I-C) = (2.5 2.5) = 0.0

b) X (Cl, Br, I) is a leaving group

pKb = 23 pKb = 22 pKb = 21 pKb = 11 pKb = -1.7

I - Br - Cl - F - HO -

30,000 10,000 200 1 0

decreasing basicity, increasing stability

increasing leaving ability

Br H 3 C

ClH 3 C

IH 3 C

The bestleavinggroups arethe weakest

bases.

The poorestleaving groupsare thestrongestbases.
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Reactions of Alkyl Halides (R-X): [S N1, S N2, E1, & E2 reactions]

There are two kinds of substitution reactions, called S N1 and S N2.When a nucleophile (electron donor, e.g., OH -) reacts with an alkyl halide,the halogen leaves as a halide

There are two competing reactions of alkyl halides with nucleophiles.

1) substitution

C C

H

X

Nu: - + C C

H

Nu

+ X-

Br R.... :

..

.. :: Br Nu:

2) elimination

+ C C

H

X

Nu: - C C+ X- + Nu H

The Nu: - replaces the halogen on the -carbon.

The Nu: - removes an H + from a b -carbon &the halogen leav es forming an alkene.

b
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S N2 stands for Substitution, Nucleophilic, bimolecular. Another

word for bimolecular is 2 nd order.

Bimolecular (or 2 nd order) means Rate = k [RX] [Nu: -] (This

is a rate equation and k is a constant).

The mechanism of an S N2 reaction is

SN2 reactions, i.e. 2nd Order Nucleophilic Substitution Reactions

C C

H

X

Nu: - + C C

H

Nu

+ X-

Note that the nuc leop hi le m ust h i t the back s ide of the -carbon.The nuc leoph i le to C bo nd fo rms as the C to X bond b reaks .

No C + in termedia te form s.

Sn2 Mechnism http://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn2_old-a.html

GIF for Sn2 http://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2_alternate.html
http://blog.oureducation.in/http://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn2_old-a.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn2_old-a.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn2_old-a.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn2_old-a.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn2_old-a.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn2_old-a.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn2_old-a.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn2_old-a.htmlhttp://blog.oureducation.in/


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2nd Order Nucleophilic Substitution Reactions, i.e., S N2 reactions

The rate of an S N2 reaction depends upon 4 factors:

1. The nature of the substrate (the alkyl halide)

2. The power of the nucleophile

3. The ability of the leaving group to leave

4. The nature of the solvent

1. Consider the nature of the substrate :

Unhindered alkyl halides will react fastest in S N2 reactions, that is:

Me >> 1 >> 2 >> 3

While a methyl halides reacts quickly in S N2 rea ctions, a 3 does not react.

The back side of an -carbon in a 3 alkyl halide is completely blocked.

O H....: C Br

..

.. :

H

H

H+

transition state

C Br .... :

H H

H

OH.... +

..

.. :Br :C

H

HH

OH....
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Me >> 1 >> 2 >> 3

Effect of nature of substrate on rate of S N2 reactions:

CH3

Br CH 3 CH 2 Br CH Br

CH 3

CH 3

C Br

CH 3

CH 3

CH 3

t-butyl bromidemethyl bromide ethyl bromide isopropyl bromide

Back side of -Cof a methyl halide

is unhindered.

Back side of -C of a1 alkyl halide is

slightly hindered.

Back side of -C of a2 alkyl halide ismostly hindered.

Back side of -C of a

3 alkyl halide iscompletely blocked .

decreasing rate of S N 2 react ion s

SPACE FILLING MODELS SHOW ACTUAL SHAPES AND RELATIVE SIZES


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The a-carbon in vinyl and aryl halides, as in 3 carbocations, are

completely hindered and these alkyl halides do not undergo S N2reactions.

CH 2 CH Br

H2

C CH Br

Br

Br

vinyl bromide bromobenzene

The overlapping p-orbitals that form the p-bonds in vinyl and aryl halidescompletely block the access of a nucleophile to the back side of the alphacarbon.

Nu: - Nu: -

Effect of nature substrate on rate of S N2 reactions:


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2. Consider the power of the nucleophile :

The better the nucleophile, the faster the rate of S N2 reactions.

The table below show the relative power or various nucleophiles.

The best nucleophiles are the best electron donors .

Reactivity Nu: - Relative

Reactivityvery weak HSO 4

-, H 2PO 4-, RCOOH < 0.01

weak ROH 1

HOH, NO 3- 100

fair F - 500

Cl -, RCOO - 20 103

NH 3, CH 3SCH 3 300 103

good N 3-, Br - 600 10 3

OH -, CH 3O- 2 10 6

very good CN -, HS -, RS -, (CH 3)3P:, NH 2- ,RMgX,

I -, H -> 100 10 6

i n c r e a s

i n g

Effect of the nucleophile on rate of S N2 reactions:


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3. Consider the nature of the leaving group :

The leaving group usually has a negative charge

Groups which best stabilize a negative charge are the best leaving groups,i.e., the weakest bases are stable as anions and are the best leaving groups.

Weak bases are readily identified. They have high pKb values.

Iodine (-I) is a good leaving group because iodide (I -) is non basic.

The hydroxyl group (-OH) is a poor leaving group because hydroxide (OH -)is a strong base.

Effect of nature of the leaving group on rate of S N2 reactions:

pKb = 23 pKb = 22 pKb = 21 pKb = 11pKb = -1.7

pKb = -2 pKb = -21I- Br - Cl- F- HO- RO - H2N-

30,000 10,000 200 1 0 0 0

Increasing leaving ability


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4. Consider the nature of the solvent :There are 3 classes of organic solvents:

Protic solvents , which contain OH or NH2 groups. Protic solvents slowdown S N2 reactions.

Polar aprotic solvents like acetone, which contain strong dipoles but no OHor NH2 groups. Polar aprotic solvents speed up S N2 reactions.

Non polar solvents , e.g., hydrocarbons. S N2 reactions are relatively slow innon polar solvents.

Effect of the solvent on rate of S N2 reactions:

Protic solvents (e.g., H 2O, MeOH, EtOH, CH 3COOH, etc.) cluster around the Nu:-(solvate it) and lower its energy (stabilize it) and reduce its reactivity via H-bonding.

X:-

H

H

HH OR

OR

OR

RO

+

+

+

+

-

-

-

-

A solvated anion (Nu:-) has reduced nucleophilicity,reduced reactivity and increased stability

A solvated nucleophile has difficulty hitting the -carb on.
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Polar Aprotic Solvents solvate the cation counterion of the nucleophile butnot the nucleophile


Polar aprotic solvents solvate metal cationsleaving the anion counterion (Nu: -) bare andthus more reactive

CH3C O

O: :.... :

_ Na +

Na +

N C CH 3

N C CH 3

N C CH 3NCH3C

-

-

-

-

+

+

+

+

+ CH3C O

O: :.... :

_

CH3CN::

..

..

:


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Non polar solvents (benzene, carbon tetrachloride, hexane, etc.) donot solvate or stabilize nucleophiles.

S N2 reactions are relatively slow in non polar solvents similar to that in protic solvents.


benzene

C

Cl

ClCl Cl

carbontetrachloride

CH 3CH 2CH 2CH 2CH 2CH

n-hexane


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Stereochemistry of S N2 Reaction

Cl

R1

R 3 R2

Nu

Transition State

Energy Maxima

BondForming

2

1 2

1

sp 2

BondBreaking

R1

R2R3

Nu Cl

Inversion of Conf igura t ion

Nucleophile attacks from behind the C-Cl -bond. This is where the *-antibonding orbital of the C-Cl bond is situated. Hence inversion of configuration takes place. This inversion is called Walden Inversion

Rate = k [R-Hal][Nu]

R 1

R 2 R 3

C l Nu

sp 3

B i m o l e c u l a r P r o c e s s

RateDeterminig

Step
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http://chemistry.boisestate.edu/rbanks/or ganic/sn2.gif


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http://www.personal.psu.edu/facult y/t/h/the1/sn2.htm


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http://www.bluffton.edu/~bergerd/classes/C EM221/sn-e/SN2-1.html


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Transition States

A + B

E

nergy

Reaction Coordinate

A + B

C + D

[A .B]

Transition

State

EnergyMaxima

Rate = k [A][B]

G

G o


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1st Order Nucleophilic Substitution Reactions, i.e.,S N1 reactions

C

CH 3

H3C

CH 3

Br + Na + I- C

CH 3

H3C

CH 3

I + Na + Br -3rapid

3 alkyl halides are essentially inert to substitution by the S N2mechanism because of steric hindrance at the back side of the -carbon.

Despite this, 3 alkyl halides do undergo nucleophilic substitution

reactions quite rapidly , but by a different mechanism, i.e., the S N1mechanism.

S N1 = Substitution, Nucleophilic, 1st order (unimolecular).

S N1 reactions obey 1st order kinetics, i.e., Rate = k [RX].

The rate depends upon the concentration of only 1 reactant, thealkyl halide-not the nucleophileThe order of reactivity of substrates for S N1 reactions is the reverseof S N2

3 > 2 > 1 > vinyl > phenyl > Me

R3C-Br R 2HC-Br RH 2C-Br CH 2=CH-Br -Br H 3C-Br

increasing rate of S N1 reactions
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The mechanism of an S N1 reaction occurs in 2 steps:

Reaction Steps

1. the slower, rate-limiting dissociation of the alkyl halide forming a C+intermediate

2. a rapid Nucleophilic attack on the C+

Mechanism of S N1 reactions

C

CH 3

H3C

CH 3

3Br ....

: + Na + Br -C

CH 3

H3C

CH 3

I....

:1.

Br --

C

CH 3

H3C

CH 3

+

3 C +

rapid

Na + I -....: :

2.

Note that the nuc leophi le i s not invo lved in the s lo wer, ra te-l imi t ing s tep .

Sn1 Mechanism http://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn1_anim.html

GIF Sn1 http://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.html
http://blog.oureducation.in/http://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn1_anim.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn1_anim.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN1_alternate.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn1_anim.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn1_anim.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn1_anim.htmlhttp://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/sn1_anim.htmlhttp://blog.oureducation.in/


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The rate of an S N1 reaction depends upon 3 factors:1. The nature of the substrate (the alkyl halide)

2. The ability of the leaving group to leave3. The nature of the solventThe rate is independent of the power of the nucleophile.

1. Consider the nature of the substrate :Highly substituted alkyl halides (substrates) form a more stable C+.

The Rate of S N1 reactions

C

H

H

H +C

CH 3

H

H +C

CH 3

H

H3C +C

CH 3

CH 3

H3C +

tertiary3

secondary2

primary1

methyl

morestable

lessstable

> > >

increasing rate of S N1 reactions


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Alkyl groups are weak electron donors. They stabilize carbocations by donating electron density by

induction (through bonds )

They stabilize carbocations by hyperconjugation (by partial overlap of the alkyl C-to-H bonds with the empty p-orbital of the carbocation).

Stability of Carbocations

C

CH3

CH3

H3C +

Inductive effects:Alkyl groups donate (shift) electrondensity through sigma bonds toelectron deficient atoms.This stabilizes the carbocation.

vacant p orbitalof a carbocation

sp 2hybridizedcarbocation

Csp 3-Hssigma bondorbital

overlap (hyperconjugation)

HYPERCONJUGATION

+C C

.. H

H

H


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Allyl and benzyl halides also react quickly by S N1 reactions

because their carbocations are unusually stable due to theirresonance forms which delocalize charge over an extended system

Stability of Carbocations

H2C CH +CH2 CH2HCH2C+

1 allyl carbocation

H2C CH +CHR CHRHCH2C+

2 allyl carbocation

2 benzylic1 benzylic

CH

R

+C

H

H

+C

H

HC

H

HC

H

H

+ +

+


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Relative Stability of All Types of Carbocations

2 allylic

>>

3 allylic

> > >

3 C +

CCH3

CH3

CH3

+

CH2 CH CHR+CH2 CH CR 2

+

C R 2+

3 benzylic

C HR+

2 benzylic

1 allylic

CCH3

CH3

H+

2 C +

CH2 CH CH 2+

C H 2+

1 benzylic

1 C +

CCH3

H

H+

+

+

CH

H

Hmethyl C

+

phenyl>

CH2 CH+

+vinyl C

Increasing C+ stability and rate of S N1 reaction

Note that 1 allyli c and 1 benzylic C+s are about as stabl e as 2 alkyl C+s .

Note that 2 allyli c and 2 benzylic C+s are about as stabl e as 3 alkyl C+s .

Note that 3 allyli c and 3 benzlic C+s are more stable than 3 alkyl C+s

Note that phenyl and vinyl C+s are unstable. Phenyl and vinyl halides do not

usually react by S N 1 or S N 2 reactions
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2. Consider the nature of the leaving group : The nature of the leaving group has the same effect on both S N1 and S N2

reactions.The better the leaving group, the faster a C+ can form and hence the faster will

be the S N1 reaction.The leaving group usually has a negative charge

Groups which best stabilize a negative charge are the best leaving groups,

i.e., the weakest bases are stable as anions and are the best leaving groups. Weak bases are readily identified. They have high pKb values .

Effect of nature of the leaving group on rate of S N1 reactions:

pKb = 23 pKb = 22 pKb = 21 pKb = 11 pKb = -1.7 pKb = -2 pKb = -21

I- Br - Cl- F- HO- RO - H2N-

30,000 10,000 200 1 0 0 0

Increasing leaving ability

Iodine (-I) is a good leaving group because iodide (I -) is non basic.

The hydroxyl group (-OH) is a poor leaving grou p because hydroxide(OH -) is a strong base.
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3. Consider the nature of the solvent: For S N1 reactions, the solvent affects the rate only if it influences the

stability of the charged transition state, i.e., the C+. The Nu:-

is notinvolved in the rate determining step so solvent effects on the Nu: - do notaffect the rate of S N1 reactions.Polar solvents, both protic and aprotic, will solvate and stabilize thecharged transition state (C+ intermediate), lowering the activation energyand accelerating S N1 reactions.

Nonpolar solvents do not lower the activation energy and thus make S N1reactions relatively slower


reaction r ate increases with polari ty of so lvent

The relative rates of an S N1 reaction due to solvent effects are given

(CH 3)3C-Cl + ROH (CH 3)3C-OR + HCl

H 2O 20% EtOH (aq) 40% EtOH (aq) EtOH100,000 14,000 100 1
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Solvent polarity is usually expressed by the dielectric constant , , which is a

measure of the ability of a solvent to act as an electric insulator.

Polar solvents are good electric insulators because their dipoles surround and

associate with charged species.

Dielectric constants of some common solvents are given in the following table


Name dielectric constant Name dielectric constant

aprotic solvents protic solvents

hexane 1.9 acetic acid 6.2

benzene 2.3 acetone 20.7

diethyl ether 4.3 ethanol 24.3

chloroform 4.8 methanol 33.6

HMPA 30 formic acid 58.0

DMF 38 water 80.4

DMSO 48


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Consider the nature of the Nucleophile:

The nature of the nucleophile has no effect on the rate of S N1 reactions

because the slowest (rate-determining) step of an S N1 reaction is the

dissociation of the leaving group and formation of the carbocation.

All carbocations are very good electrophiles (electron acceptors) and even

weak nucleophiles, like H 2O and methanol, will react quickly with them.

The two S N1 reactions will proceed at essentially the same rate since the

only difference is the nucleophile.

Effect of the nucleophile on rate of S N1 reactions:

C

CH 3

H3C

CH 3

Br + Na + I- C

CH 3

H3C

CH 3

I + Na + Br -3

C

CH 3

H3C

CH 3

Br + C

CH 3

H3C

CH 3

F + K+ Br -3 K+ F -


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Stereochemistry of S N1 Reaction


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Go

Energy

G G

Energy

Reaction Coordinate

A + B

D + E

C + B

ReactiveIntermediate

EnergyMinima

Rate = k [A]

Reactive Intermediates


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E

nergy

Reaction Coordinate

R 1

R2R3

Cl

R1

R3 R2

R 1

R2R3

Nu

R1

R2R3

NuReactive Intermediat

Racemisation takes place after intermediate formation
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substitution elemination reactions

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