Organic Chemistry

Ismono, FMIPA Unesa

• REAKSI KIMIA ORGANIKDapat berupa

REAKSI SUBSTITUSI REAKSI ELIMINASIDapat dikatagorikan

SN2 SN1 E2 E1

Dapat dikatagorikan

• The basic structure of testosterone (male hormone) and estradiol (female hormone) is identical.

• Both are steroids with four fused carbon rings, but they differ in the functional groups attached to the rings.

– These then interact with different targets in the body.

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Fig. 4.8

GBRP

• Deskripsi : Kajian tentang zat antara reaktif (ion karbokation, radikal bebas, ion karbanion, dan karben), faktor yang mempengaruhi kestabilan zat antara reaktif. Hubungan persamaan kinetik dengan mekanisme reaksi. Pembahasan yang terkait dengan metode kinetik, macam-macam uji mekanisme reaksi (pemerangkapan zat antara, cara stereokimia, dan pelabelan)

• Standar Kompetensi : Mahasiswa memahami peranan Orbital dalam ikatan kovalen, faktor-faktor penyebab kestabilan relatif zat antara reaktif, mekanisme reaksi, meramalkan produk-produk yang kemungkinan terjadi dan produk yang diharapkan dominan berdasarkan kontrol kinetik atau kontrol termodinamik.

No Kompetensi Dasar Materi Waktu Tugas/praktikum 1. Mahasiswa memahami

orbital dan peranannya dalam ikatan kovalen

Orbital dan Peranannya dalam Ikatan Kovalen

2 jam Pertemuan 1

Menyelesaikan soal-soal dan mengumpulkan tugas tersebut

2. Mahasiswa memahami tentang mekanisme reaksi SN2 dan faktor-faktor yang mempenga ruhi laju SN2

Mekanisme reaksi substitusi SN2

2 jam Petermuan 2

Menyelesaikan soal-soal di rumah dan dibahas di depan kelas (soal terpilih)

3. Mahasiswa memaham tentang mekanisme reaksi SN1 dan faktor-faktor yang mempenga ruhi laju reaksi SN1

Mekanisme reaksi substitusi SN1

4. jam Petermuan 3-4

Menyelesaikan soal-soal dan mengumpulkan makalah mekanis me reaksi SN2 dan SN1

4. Mahasiswa memahami tentang mekanisme reaksi E2 dan faktor-faktor yang mempenga ruhi laju reaksi E2

Mekanisme reaksi E1 dan E2

4 Jam Petermuan 4-5

Menyelesaikan soal-soal dan mengumpulkan tugas dan dinahas di depan kelas (soal terpilih)

Hydrogen Orbital Diagram• Orbital diagrams

– Show the sublevels and orbitals that can exist at each principal energy level

– Each box represents an orbital

– Groups of boxes represent sublevels

• In the hydrogen atom only, the sublevels within a principal energy level all have the same energy.

7 -

Multielectron Orbital Diagram• In the multielectron atoms, the sublevels within a

principal energy level have different energy levels.

7 -

Orbital Diagram Rules– Aufbau principle

• Electrons fill orbitals starting with the lowest-energy orbitals.

– Pauli exclusion principle• A maximum of two electrons can occupy each orbital, and

they must have opposite spins.

– Hund’s rule • Electrons are distributed into orbitals of identical energy

(same sublevel) in such a way as to give the maximum number of unpaired electrons.

• Electrons are always filled in their ground state, or lowest energy state.

7 -

Filling Orbital Diagrams

7 -

Pg. 251 (Carbon’s orbital diagram)

Orbital Diagrams for the 1st Ten Elements

7 -

Hydrogen building block

Energy diagram for the hydrogen molecule. Combination of two atomic orbital Ψs gives two molecular orbitals, Ψmolec and Ψ* molec. The energy of Ψmolec is lower than that of the separate atomic orbitals, and in the lowest electronic energy state of molecular hydrogen it contains both electron

(Ψ 1a + Ψ*1sb)2 = (Ψ1sa)2 + 2 Ψ1sa Ψ*1sb + (Ψ*1sa)2

σ*

σ

Atomic Orbital

Ψ1sAΨ1sB

Atomic Orbital

Molecular Orbital

Energy

Intermolecar distance (r)

No attraction

attraction

Repulsion

Most stable

r = 0,74 Å

The Potential energy of hydrogen molecule (435 kJ/mol) as an function of intermolecular distantace

bonding

Anti bonding

2s 2px 2pz2py1s sp3 sp3 sp3 sp3

109.5o

Promote Hybridize

x

z

y

Methane: Carbon

Karakteristik s = 25%

Panjang Ikatan C – C = 1,54Ao

Panjang Ikatan C – H = 1,09Ao

Logically of Nucleophilic Substitution Reaction

Mechanisms

Logically of Nucleophilic Substitution Reaction Mechanisms

1. The nucleophile might enter and bond, and then the halide ion would leave

2. The nucleophile might attack and bond at exactly the same time the halide ion is leaving

3. The Halide ion might leave, followed by the entrance and bonding of the nucleophile.

The first path requires that Carbon accommodate five bond and thus is not a realistic possibility. However, the other two ideas are sound, and both are common mechanisms for nucleophilic substitutions. The second possibility as know as the SN2 mechanisms and the third is referred to as the SN1 mechanisms.

Some Concepts in Organic

1. Reaction equation an equation that show what happened in chemical reaction by showing reactants and product

2. Substitution reaction a reaction in which an atom or group on a molecule is replaced by another atom or group (Nu)

3. Elimination reaction a reaction in which atoms or groups are removed from adjacent atoms to from a double or tri bond

4. Addition reaction a reaction in which atoms and groups add to adjacent atoms of multiple bond.

• Reaction Mechanism a step-by-step description of how a chemical reaction occur.

• Reaction Intermediate an unstable, short lived species formed during a chemical reaction: example are carbocations, free radicals and carbanions

• Carbocation a species with carbon that has only three bonds and six outer shell electron, and a positive

• Free Radical a neutral species with a carbon that has only three bonds and seven outer-shell electrons, one of which, is unpaired

• Carbanion a species with carbon that has only three bonds and eight outer shell electron, including one nonbonding pair, and a negative charge

• Homolytic Cleavage, bond cleavage in which the bonding electron are evenly divided between the two part parting atom

• Heterolytic Cleavage, bond cleavage in which the bonding electron are unevenly divided between the two part parting atom

• Nucleophile, a species with electron availability that donates electrons to electrophiles in a chemical reaction. Nucleophile are Lewis Based

SUBSTITUTION REACTIONS

•Competition Reaction (Substitutions VS Elimination)

Substitution and Elimination

• If an sp3 C is bonded to electronegative atom Substitution reactions and

Elimination reactions are possible

This chapter is all about substitution

SN2 and SN1 Reactions

SN2 - Reaction – bonds break and form at the same time

example

SN1 - CX bond breaks, forming a C+ then reacts with a nucleophile

XC+

C + + X-

NuCC + + Nu:

SN1

SN2

Nucleophilic Substitution Reactions

Either mechanism depends on the:• structure of the alkyl halide• reactivity of the nucleophile• concentration of the nucleophile• The solvent in which the Rx is carried out• The leaving group

SN2 Mechanism

• It’s a Substitution Reaction (S)

• It’s Nucleophilic (N)

• It’s rate is second order (2)– Called bimolecular (rate is dependent on 2 reactants)

• (Substitution Nucleophilic Bimolecular)

CH3Br + HO - CH3OH + Br-

methyl bromide methyl alcohol

Rate = k [RX] [Nu:]

(Because rate is dependent of BOTH RX and Nu: it is 2nd. order.)

The SN2 Mechanism

1. SN2 is substitution nucleophilic bimolecular; the one step nucleophilic substitutions mechanism

2. Bimolecular term that describes a reaction rate that depends on the concentration of two species.

3. Rate SN2: k[RX][Nu:] General rate equation for SN2

4. Concerted reaction

Transition state• Activation Energy is higher then

Reactant and product…..

TsTs

CC

H

H H

H

H Br CC

H

H H

H

H OH

:OH-

Nucleophilic Substitution – SN2 Mechanism

(Concerted reaction)

Rate = k[C2H5Br][:OH-]

:Br-

+ _

(NB Transition state)

SN2 Mechanism

• SN2 Mechanism involves a “backside attack”

SN2 Mechanism

The “backside attack” causes an Inversion of Configuration

Careful now….. Doesn’t mean R becomes S – new atoms are involved

HO:- + CH3Br CH3OH + Br-

Transition State Rate = k[CH3Br][OH-]

H

HO C Br H H

CH3 CH3 CH3

HO- C – Br HO C Br HO – C + Br-

H H CH2CH3 H

CH3CH2 CH2CH3

(R)-2-Bromo Butane Transition state showing Pure enantiomerPure enantiomer nucleophile attacking from optically active; Optically active opposite side of leaving inverted mirror image bromide configuration

(S)-2-Butanol

Steric Hindrance

• Groups that block the path from the nucleophile to the electrophilic atom produce steric hindrance

• This results in a rate differences or no reaction at all

methyl halide ethyl halide isopropyl halide t-butyl halide

Steric Hindrance

• Activation Energy is higher due to steric hindrance…..

Substitution Reactions Depend on a Good Leaving Group

• R-F alkyl fluorides• R-Cl alkyl chlorides• R-Br alkyl bromides• R-I alkyl iodides• Alkyl Halides make good “leaving groups”

– They are easily displaced by another atom– They allow the Conversion of alkyl halides to other functional

groups

SN2 Mechanism

• The Leaving Groups also affects rate• RI reacts fastest, RF slowest

– Iodide is the best “leaving group”– Fluoride is the worst “leaving group”

(…reacting with the same alkyl halide under the same conditions)

Basicity

• The weaker the basicity of a group, the better the leaving ability.

(Lewis base = e- pair donor)

– Leaving ability depends on basicity because a weak base does not SHARE its e- as well as a strong base.

– Weak bases are not strongly bonded to a carbon

(weak bases are GOOD leaving groups)

Nucleophiles – Strong/Weak Good/Bad

Stronger base Weaker baseBetter nucleophile poorer nucleophile

OH- > H2O

CH3O- > CH3OH-NH2> NH3

CH3CH2NH- > CH3CH2NH2 (conjugate acids)

Nucleophiles

• The strength of nucleophile depends on reaction conditions.

• In the GAS phase (not usually used), direct relationship between basicity and nucleophilicity

Solvent Effects

• In a solution phase reaction, the solvent plays a large role in how the reaction will occur

• Solvent effects can cause just the opposite of what might be the expected behavior of the nucleophile

• Solvents are categorized as either protic or aprotic

Protic SolventsProtic solvents has a H bonded to a N or O

– It is a H bonder

– Examples: H2O, CH3OH, NH3, etc

– Solvent is attracted to the Nucleophile and hinders its ability to attack the electrophile

Aprotic Solvents• Use an aprotic solvent

• Solvates cations • Does not H bond with anions (nucleophile free)• Partial + charge is on inside of molecule• Negative charge on surface of molecule (solvates

cation)• Examples include:

– DMSO (dimethyl sulfoxide)– DMF (dimethyl formamide)

– Acetone (CH3COCH3)

acetone

CH3CCH3

O

dimethyl sulfoxide

CH3SCH3

O

DMSON,N-dimethylformamide

HC N

O

CH3

CH3

DMF

Nucleophiles

• In the organic solvent phase, INVERSE relationship between basicity and nucleophilicity with a protic solvent

Question…

Nucleophiles• Solvents can solvate the nucleophile

– Usually this is NOT good because the nucleophile is “tied up” in the solvent and LESS REACTIVE.

Ion-dipole interactions

Nucleophiles• Solvents can solvate the nucleophile

(Methanol is a polar protic solvent.)

SN2 Reactions

SN2 Reactions

SN2 Reactions• SN2 reactions might be reversible

• Leaving group would become the nucleophile

• Compare basicity (nucleophile strength) to see which is a better leaving group.

• The stronger base will displace the weaker base– If basicity is similar, the Rx will be reversible

CH2CH3 Br + I- CH2CH3 I + Br-CH2CH3 Br + I- CH2CH3 I + Br-

SN2 Reactions

Compare basicity to see which is a better nucleophile.

SN1 Reactions

• Reaction of t-butyl bromide with water should be slow– water is a poor nucleophile– t-butyl bromide is sterically hinderedHowever– Reaction is a million times faster than with CH3Br

t-butyl bromide

CCH3

CH3

Br

CH3

+ H2O

t-butyl alcohol

CCH3

CH3

OH

CH3

+ HBr

t-butyl bromide

CCH3

CH3

Br

CH3

+ H2O

t-butyl alcohol

CCH3

CH3

OH

CH3

+ HBr

(Maybe not an SN2 reaction!)

SN1 Reactions•

SN1 Mechanism• Rate determining step does not involve

nucleophile

Step 2

Step 1

SN1 Mechanism

SN1 Mechanism

(CH3)2CH

C – Br

CH3CH2

CH3

Br -

(S)-2,3 dimetil-2-Bromo Butane Pure enantiomer optically active

(CH3)2CH

CH3CH2CH3

C+

Carbocation

:O:

CH3 H

Nucleophile attack planarCarbocation equally from eitherside

CH3O

(CH3)2CH

CH3

CH2CH3

C

50%(CH3)2CH

OCH3

CH3

CH2CH3

C

50%

Both inversion and retention of configuration occur equally A pair of enantiomers is the results. This is an optically inactive racemic mixture

SN1 Reactivity

• Relative Reactivities in an SN1 Reaction

1o RX < 2o RX < 3o RX

Increasing Reactivity

SN1 Stereochemistry

• Because a planer carbocation is formed, nucleophilic attack is possible on both sides, so both isomers are possible

SN1 Stereochemistry

SN1 should yield racemic mixture but it doesn’tThis is due to the steric hindrance of the leaving group

Stereochemistry• As the leaving group goes (Marvin K) it

blocks the path of any incoming nucleophiles

SN1 vs SN2

Inversion of configuration

racemization withpartial inversion

What Makes SN1 Reactions work the best

• Good Leaving Group– The weaker the base, the less tightly it is held

(I- and Br- are weak bases)

• Carbocation– How stable is the resulting carbocation?

• 3o > 2o > 1o > methyl

Increasing Stability

What Doesn’t Matter In anSN1 Reactions

• The Nucleophile• It has NO EFFECT on rate of Rx!!!

• Solvolysis Reactions • (the nucleophile is also the solvent)

Carbocation RearrangementsSince a carbocation is the intermediate, you may see

rearrangements in an SN1 Rx

No rearrangements in an SN2 Rx

Carbocation Rearrangement

• Methyl Shift

Benzylic, Allylic, Vinylic,and Aryl Halides

• Benzylic and allylic halides can readily undergo SN2 unless they are 3o – (steric hindrance)

Benzylic, Allylic, Vinylic,and Aryl Halides

• Benzylic and allylic halides can also undergo SN1 (they form stable carbocations)

• Even though 1o RX do not go SN1, 1o benzylic and 1o allylic CAN react SN1!

Vinylic,and Aryl Halides

• Vinylic halides and aryl halides– do not undergo SN1 or SN2 reactions! e- repel incoming Nucleophile

BrBr

SN1 vs SN2 Review

SN1 vs SN2

Methyl, 1o RX …2o RX …3o RX …

Vinylic, aryl RX …1o, 2o benzylic, allylic RX …

3o benzylic, allylic RX …

SN2 only

SN1 and SN2

SN1 only

neither SN1 nor SN2

SN1 and SN2

SN1 only

Role of the SolventIn an SN1, a carbocation and halide ion are formed

– Solvation provides the energy for X- being formed– In SN1 the solvent “pulls apart” the alkyl halide– SN1 cannot take place in a nonpolar solvent or in

the gas phase– Increasing the polarity of the solvent will

INCREASE the rate of Rx if none of the REACTANTS are charged.

– If reactants are charged it will DECREASE the rate.

Role of the Solvent

• So….• In an SN1 reaction, the reactant is RX. The

intermediate is charged and is STABILIZED by a POLAR solvent

A POLAR solvent increases the rate of reaction for an SN1 reaction.

(However, this is true only if the reactant is uncharged.)

*

Role of the Solvent In SN2

• In an SN2 reaction, one of the reactants is the nucleophile (usually charged).

• The POLAR solvent will usually stabilize the nucleophile.

A POLAR solvent decreases the rate of reaction for an SN2 reaction.

(However, this is true only if the nucleophile is charged.)

Polar Aprotic Solvents

• Polar Aprotic Solvents include:– DMF N,N-dimethylformamide

– DMSO dimethylsulfoxide

– HMPA hexamethylphosphoramide

– THF Tetrahydrofuran– And even… acetone

Polar Aprotic Solvents

Polar Aprotic Solvents – do not H bond– solvate cations well– do NOT solvate anions (nucleophiles) well– good solvents for SN2 reactions

Polar Aprotic Solvents

• DMSO• DMF• Acetone• HMPA

Nucleophile Review

strong

weak

Br-, I-

HO-, CH3O-, RO-

CH3S-, RS -

CH3CO2-, RCO2

-

H2OCH3OH, ROHCH3CO2H, RCO2H

NH3, RNH2, R2NH, R3NCH3SH, RSH, R2S

EffectivenessNucleophile

moderate

CN-, N3-

SN1/SN2 Problems -1

• Predict the type of mechanism for this reaction, and the stereochemistry of each product

+

+ +

OH

Cl

OCH3

CH3CHCH2CH3

CH3CHCH2CH3

CH3CHCH2CH3

CH3OH/H2O

HCl(R)-enantiomer

SN1/SN2 Problems -1

• Predict the type of mechanism for this reaction, and the stereochemistry of each product

+

+ +

OH

Cl

OCH3

CH3CHCH2CH3

CH3CHCH2CH3

CH3CHCH2CH3

CH3OH/H2O

HCl(R)-enantiomer

SN1/SN2 Problems -2

• Predict the mechanism of this reaction

+

+

DMSOCH3

CH3

CH3CHCH2CN

CH3CHCH2Br Na+CN-

Na+Br-

SN1/SN2 Problems -2

• Predict the mechanism of this reaction

+

+

DMSOCH3

CH3

CH3CHCH2CN

CH3CHCH2Br Na+CN-

Na+Br-

SN1/SN2 Problems -3

• Predict the mechanism. If the starting material has the R configuration, predict the configuration of product

+

+

acetone

Br

SCH3

CH3CHCH2CH3 CH3S-Na+

CH3CHCH2CH3 Na+Br-

SN1/SN2 Problems -3

• Predict the mechanism. If the starting material has the R configuration, predict the configuration of product

+

+

acetone

Br

SCH3

CH3CHCH2CH3 CH3S-Na+

CH3CHCH2CH3 Na+Br-

SN1/SN2 Problems -4

• Predict the mechanism

+ acetic acidBr

OCCH 3

O

O

CH 3 COH

+ HBr

SN1/SN2 Problems -4

• Predict the mechanism

+ acetic acidBr

OCCH 3

O

O

CH 3 COH

+ HBr

SN1/SN2 Problems -5

• Predict the mechanism

+ toluene

Br-

(CH3)3PCH3(CH2)5CH2Br

CH3(CH2)5CH2-P(CH3)3

+

SN1/SN2 Problems -5

• Predict the mechanism

+ toluene

Br-

(CH3)3PCH3(CH2)5CH2Br

CH3(CH2)5CH2-P(CH3)3

+

END