Wittig reagentDiazopropaneBOP Reagent

BINUJA SS

FIRST YEAR M.PHARM

WITTIG REAGENT

• Triphenyl phosphine alkylidienes

Alternative names

• Triphenylphosphoniumylide

• Alkylidienephosphorane

• reagent for the synthesis of alkene from ketones

and aldehydes.

R1 = H

R2 = -CH3 , C2H5,C4H9

FORMS OF WITTIG REAGENT

• described in the phosphorane form or the ylide form:

GENERAL PREPARATION OF WITTIG REAGENT

• Ph3P + RCH2X→ [Ph3P+CH2R]X−

Phosphonium salt

• [Ph3P+CH2R]X− + C4H9Li → Ph3P=CHR + LiX +

C4H10 Wittig reagent

Example :

• Triphenylphospthinemethylidine OR Methylidinephosphoranes.

• Prepared by

• (C6H5)3P + CH3Br → [(C6H5)3P+CH3]Br− →

methyl bromide methyl phosphonium salt

(C6H5)3P=CH2 + LiBr + C6H6

Methylidiene phosphoranes

GENERAL MECHANISM OF WITTIG REAGENT

APPLICATIONS

1. Preparation of Olefins

• Wittig reagent provides a method for the

synthesis of olefins.(Wittig reaction)

SYNTHESIS OF INDOLE

• MECHANISM

Synthesis of natural products

• Synthesis of squalene

Synthesis of bisabolene

Synthesis of beta- carotene .

DIAZOPROPANE

• Diazo refers to a type of organic compound called

diazo compound that has two linked nitrogen atoms

(azo) as a terminal functional group.

• reagent is used for the cyclopropanation of alkenes.

Preparation

• 2-diazopropane is most commonly prepared by the oxidation

of Acetohydrazone with Mercury(II) Oxide in the presence of

base.

APPLICATIONS

1. Cyclopropanation of Alkenes

• prepare gem-dimethylcyclopropyl derivatives.

• This reagent will readily undergo cycloadditions

with alkenes to provide the

corresponding pyrazolines which can be induced

to lose N2 to provide the desired cyclopropanes.

Synthesis of ketone.

tropolone8,8-dimethyl-6-((propan-2-

yl)oxy)bicyclo octan-7-one

Syntheis of aristolone

• It is a sesquiterpenes isolated from both the roots of the

Chinese fairy root and rhizome of Canadian ginger and widely

used in traditional medicine.

BENZTRIAZOL-1-YLOXY) TRIS

(DIMETHYLAMINO) PHOSPHONIUM

HEXAFLUORO-PHOSPHATE (BOP)

• commonly used in the synthesis of peptides.

• Solubility: insoluble in H2O; soluble THF,

CH2Cl2, MeCN, acetone, DMF, NMP, DMSO.

• HMPA

APPLICATIONS

1. Peptide coupling

• Peptide bond formation is a nucleophilic substitution reaction

of an amino group (nucleophile) and a carboxyl group via a

tetrahedral intermediate.

• BOP is a very efficient reagent which allows in situ

formation of hydroxybenzotriazolyl esters.

MECHANISM OF COUPLING REACTION WITH BOP

• A tertiary amine is required to generate the carboxylate anion

of the amino acid, which then attacks the phosphorus atom of

BOP. The resulting intermediate A rearranges to form the

hydroxybenzotriazolyl ester B, which is then attacked by the

amine component to form the amide product D via the

stabilized hydrogen-bonded intermediate C.

2. Esterification

• Treatment of N-protected amino acids with phenol, and BOP

in the appropriate solvent (DCM, MeCN, DMF) affords the

corresponding phenyl esters.

3. Lactam Cyclization.

• Cyclization of b-amino acids to b-lactams is efficiently

effected by treatment with BOP .The present method appears

to be limited to the formation of b-lactams from N-

unsubstituted b-amino acids (R1 = R2 = R3 = R5 = H, R4 = Me)

4.Amidation

Preparations include

• N,O-dimethyl hydroxamates of amino acids and

peptides (precursors of chiral peptidyl aldehydes),

• heterocyclic amide fragments in the synthesis of macrolide and

porphyrin models,

• dansylglycine anhydride as a mixed sulfonic-carboxylic imide by

dehydration-cyclization of dansylglycine.

• selective monoacylation of heterocyclic diamine in carbohydrate

series.

REFERENCE

• Advanced organic chemistry reactions,mechanisms by Jerry

march, 4th edition,p.no: 956-962.

• Reactions and reagents by O.P.Agarwal, p.no.840-844

• Organic chemistry by Robert Thornton Morrison, Robert Neilson

Boyd, Saibal Kanthi Bhattacharjee, 7th edition, p:no 331-334

• https://en.wikipedia.org/wiki/Diazo#From_amines

• http://onlinelibrary.wiley.com/diazopropane

• http://www.sciencedirect.com/science/article/pii/S00086215008047

23

• http://www.brainyresort.com/en/wittig-reaction-

mechanism/

• https://www.google.co.in/search?dcr=0&q=peptide+bo

nd+characteristics

• https://en.wikipedia.org/wiki/BOP_reagent

• http://www.sciencedirect.com/science/article/pii/S0040

403900772571

THANK YOU……..