M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

28
Synthetic reagents Dr. L. Satish Kumar Achary Asst. Professor Department of Chemistry CV Raman Global University Advanced Organic Chemistry M.Sc. 3 rd sem Organometallic reagents

Transcript of M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

Page 1: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

Synthetic reagents

Dr. L. Satish Kumar Achary

Asst. Professor

Department of Chemistry

CV Raman Global University

Advanced Organic ChemistryM.Sc. 3rd sem

Organometallic reagents

Page 2: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

Contents

➢ Organosilicon

➢ Synthesis.

➢ Applications.

➢ Organotin

➢ Synthesis.

➢ Applications.

➢ Tebbe reagent2

Page 3: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

❑ Organosilicon

3

Trimethylsilyl chloride

(TMSCl)

tert-butyldimethylsilyl chloride

(TBDMSCl)

Diphenylmethylsilyl

chloride (DPMSCl)

Triisopropylsilyl chloride

(TMSiCl)

SiSi

Si Si

Page 4: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

4

❑ Si forms weaker bond with electropositive elements w.r.t C.

❑ Si has low E.N than C. Thus C-Si bond is polar.

❑ C-Si bond length 1.89 Å, steric interaction between Nu- and

substrate is less. C-C bond length 1.53 Å.

❑ Silicon has vacant d-orbital which provides a target for Nu-.

C-Si

C-F

C-Cl

C-OH

F-

Cl-

OH-

StableNaF, HF, KF, nBu4NF,

NaCl, HCl, NaOH,

KOH

❑ Silicon stabilizes α-carbanion with vacant d-orbital and β-carbocation with σ-bonding orbital.

Page 5: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

5

❑ Synthesis

SiCl4

Chloro compounds are the starting materials for the preparation of

organosilicon compound.

3CH3MgCl (CH3)3SiCl+

❑ Applications

(1) As nucleophilic reagent for O-C bond cleavage

Ether reacts with the reagent to afford the alkyl iodide and

trimehylsilyl ether.

+ +

+

Ether

Page 6: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

6

+

TMSI TMSI

Epoxide

Epoxides give corresponding alkene.

Page 7: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

7

Acetal

Acetal can be converted in to ketones.

(2) In nucleophilic addition reaction

Addition reaction with carbonyl compound.

α-iodotrimethylsilyl ester

Page 8: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

8

(3) Protecting group for alcohols as TMS ester

TMSCl (1.2 equvalent) TMSCl (1.3 equvalent)

t-butyldimethylsilyl halide (TBDMS-X) is a bulky reagent which

preferabily protect primary alcohol with imidazole in DMF.

TBDPSCl

Imidazole/DMF

Page 9: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

9

1. TBDMSC

2. DDQ

3. Cl-

Deprotection can easily be done by the treatment of tetra-n-

butaylammonium flouride (TBAF), citric acid and Cl-.

TBAF/Et3N

CH2Cl2

Page 10: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

10

Silylenol ethers

Trimethylsilyl enol ether of aldehyde and ketones are usually

formed from carbonyl compound. An additional base is used.

Me3SiI/Et3N

DMF

Me3SiI/Et3N

DMF

Product depends upon base.

If base is bulkier, less substituted sillyl enol ether is the major

product. (LDA)

If base is small, more substituted sillyl enol ether is the major

product. (Et3N)

Page 11: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

11

Regioselectivity

Alkylation of carbonyl compound

1.Base, 2. R3SiX

3. R-X, 4. H3O+

Page 12: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

12

1.LDA, 2. Me3SiX

3. CH3-X, 4. H3O+

1. Et3N, 2. Me3SiX

3. Ph--X, 4. H3O+

Page 13: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

13

Peterson’s olefination (α-carbanion)

Li-Mg derivative of α-silylCarbonyl

CompoundOlefins

Alkenyl silane(β-carbocation)

Alkenyl silane undergoes electrophilic substitution reaction via β-

carbocationE+

E+X-

Page 14: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

14

Electrophillic substitution reaction catalyzed by Lewis acid.

AlCl3

AlCl3

AlCl3

Page 15: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

15

Allyl silane (β-carbocation)

E+ X-

Allyl silane undergoes electrophilic substitution reaction via β-

carbocation.

Electrophillic substitution reaction catalyzed by Lewis acid.

AlCl3

AlCl3

Page 16: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

16

Bu3–Sn–HTributyltin hydride

❑ Organotin

Sn has more metallic character with +4 oxidation state and forms

stable organic compounds.

Size if Tin is larger than Si and C due to which the bond between

Sn and C can be easily polarized.

❑ Synthesis

4Bu3SnCl

Tributyltin hydride is prepared from tributyltin chloride and LiAlH4.

LiAlH4+ 4Bu3SnH LiAlCl4

+

Tributyltin hydride is generally used as reducing agent and used

as source of hydrogen radical.

Initiator: AIBN (Azobisisobutyronitrile).

Page 17: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

17

❑ Applications

(1) Replacement of halo group

Tributyltin hydride replaces halo group from all organo halo

compounds.

R-X R-HBu3Sn-H

AIBN

X = F, Cl, Br, I.

Bu3Sn-H

AIBN

Bu3Sn-H

AIBN

Bu3Sn-H

AIBN

Page 18: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

18

Bu3Sn-H

AIBN

Bu3Sn-H

AIBN

Reactivity order

Benzyl halide > allyl halide > 3° alkyl halide > 2° alkyl halide >

1° alkyl halide > aryl halide > Vinyl halide > Alkenyl halide.

Bu3Sn-H

AIBN+ +

If halocompound having unsaturation, substitution may

accompanied by cyclisation.

Page 19: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

19

Bu3Sn-H

AIBN +

Bu3Sn-H

AIBN

(2) Replacement of nitro group

Tributyltin hydride replaces nitro group from new C-C bond.

Bu3Sn-H

AIBN

Page 20: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

20

(2) Replacement of sulphide group

Bu3Sn-H

AIBNR-SR1 R-H

Bu3Sn-H

AIBN

Bu3Sn-H

AIBN

Bu3Sn-H

AIBN

If there is an unsaturation in the sulphide, replacement of sulphide

followed by cyclization takes place.

Page 21: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

21

(2) Reduction of acid halide

Bu3Sn-H

AIBN

Acid halide gives aldehydes.

(3) Reduction of carbonyl compound

Bu3Sn-H

AIBN

Bu3Sn-H

AIBN

Carbonyl compound converted into alcohol.

Page 22: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

22

❑ Tebbe reagent

❑ The tebbe reagent is the organometallic compound.

❑ It is used in the methylenation of carbonyl compounds.

❑ Formula :C13H18AlClTi

❑ Synthesis

Titanocene dichloride reacts with trimethyl aluminium in toluene.

Me3Al

Page 23: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

23

❑ Applications

❑ Methylation of carbonyl compound

base or

without

base❑ Mechanism in presence of base

Page 24: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

24

❑ Mechanism in absence of base

Page 25: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

25

❑ Methylation of amides

Page 26: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

26

❑ Reactivity of carbonyls

> > >

Page 27: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

27

1 eq.

Page 28: M.Sc. 3rd sem Advanced Organic Chemistry Synthetic reagents

28