reagents in organic synthesis

REAGENTS IN ORGANIC SYNTHESISREAGENTS IN ORGANIC SYNTHESISMr. Anand S Burange,Institute Of Chemical Technology, Matunga , Mumbai-400019E-mail: [email protected]

Lecture at KTHM College, Nashik on 15th September 2012

WHAT IS A CHEMICAL REACTION?WHAT IS A CHEMICAL REACTION?

Chemical reaction is an effective interaction between two or more molecules/atoms /ions leading to the formation of new compound(s).

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Entry Reagent

1 NaNH2/NH3

2 1,3-propan-dithiol

3 Methylmethyl thiomethyl sulfoxide

4 OsO4, KMnO4

5 NaIO4

6 LTA

7 m-CPBA, Hydrogen peroxide

8 Ozone

9 LAH/NaBH4

10 DIBAL-H and solvent effect

11 Diethyl oxalate

12 Simmon’s Smith Vs Stabilized sulphur ylid

13 Abnormal Witting

14 NaNO2-/HCl (Semi-pinacolone rearrangement)

Role of anti-pariplanar relationship

15 Organoborane and hyperconjugation

16 Pph3 or P(OEt)3 and organosilane reagent

17 Diazomethane

18 PhSeBr

19 MeLi

Reagents to be covered……


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NaNH2/NH3

Sodamide can be prepared by adding sodium metal to ammonia.

Sodium metal can easily react with any active proton donor with the release of hydrogen gas.

NaNH2/NH3 obtained can be used for benzyne mechanism while NaNH2/NH3 in ethanol is used

for Birch reduction.


5 Lecture at KTHM College, Nashik on 15th September 2012

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i. Cl-PO(OEt)2/NaH ii. NaNH2/NH3 (Via Benzyne)

i. NaNH2/NH3

ii. -CH(CO2Et)2

OH-/340o C

NaNH2/NH3


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1,3-propan-dithiol

1,3-propan-dithiol is used to change the polarity of carbonyl carbon of aldehydes in order to make it

nucleophilic by using LDA as a base. This change in polarity is called as umpolung.

Using this concept, we can easily prepare any cyclic ketones like cyclopropanone, cyclobutanone, etc.

Protected form of formaldehyde

Again LDA is used to get which on deprotection using acid/ Hg2+ yields


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Predict alkyl halide required with 2 eq. of LDA….

BrCH2CH2Br

BrCH2CH2CH2Br

BrCH2CH2CH2CH2Br

BrCH2CH2CH2CH2CH2Br


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Methylmethyl thiomethyl sulfoxide

-CHO group can be introduced at a beta position of enone system can be asses by using methylmethyl thiomethyl sulphoxide

i. LDA

iii. H3O+/Hg2+


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Baeyer- Villiger Oxidation and migratory aptitude

Per acid

Why electrophilic ?

Stable carboxylate anion Lecture at KTHM College, Nashik on 15th September 2012

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Various per acids used for Baeyer Villiger oxidation and epoxidation reactions

Migratory aptitude in Baeyer-Villiger Oxidation Reaction

H> phenyl > tert-alkyl> sec-alkyl > primary alkyl > methyl


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Bartlett has proposed one step mechanism for epoxidation of alkene using per-acid


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OsO4 OR KMnO4 OR OsO4/ NMO OR K2OsO4 /NMO

m-CPBA

CH2I2/ Zn-Cu (Simmon’s Smith)

I2/ AgOAc (Prevost) OR m-CPBA followed by hydrolysis


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Some selectivity aspects during epoxidation reactions…..

50:50 both stereo-isomers are formed

Stereoselectivity


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Cleavage of 1,2-diols

No CleavageNaIO4 is selective for only cis-diol

LTA breaks both cis and trans diols

Vs


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Ozonolysis at different conditions…

O3 , CH2Cl2

Zn, Me2S

O3 , CH2Cl2

NaBH4 OR LAH

O3 , CH2Cl2

H2O2

Mechanism involves formation of primary ozonoid which on homolysis gives carbonyl oxide radical.

Carbonyl oxide radical on dimerization gives tetraoxane which on breaking yields corresponding carbonyl.


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DIBAL-H and Solvent-Effect

It’s a neutral aluminium hydride containing only one

hydride species. It’s a convenient reagent for reducing

carboxylic acids to alcohols. It can reduce esters to

alcohols and aldehydes selectively. Amides and nitriles

also yields aldehydes


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In Polar solvent


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In non-polar solvent

Stable at low temperature and recovered at -78oC

H2O

H3O+


Lecture at KTHM College, Nashik on 15th September 2012 21

NaBH4 Vs LAH

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Simmons-Smith Cyclopropane Synthesis

It has been developed by H.E. Simmons and R.D. Smith of the DuPont Company. During this

synthesis diiodomethane and zinc-copper couple are stirred together with alkene. The

diiodomethane and zinc react together to produce carbene like species called as carbenoid

which brings stereospecific addition of CH2 directly to the double bond.

Simplest carbene : Methylene

:CH2

Can be easily prepared by thermolysisor by irradiating diazomethane gas.


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Epoxidation and cyclopropanation of alpha-beta unsaturated enone systems

H2O2/OH-Me2SOCH2

-


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Unstabilized sulphur ylids are useful to convert carbonyls to respective epoxides

+ Me2S

Application of unstabilized sulphur ylid


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Diazomethane for ring expansion

Diazomethane is a poisonous gas. It must be handled with great care.

CH2N2

Needle like nucleophile

Structure:


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Epoxide is a product of side-reaction occurs during this reaction


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!!ANTI PERIPLANAR RELATIONSHIP!! / Elimination reaction


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NaNO2-/HCl (Semi-pinacolone rearrangement)


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Predict the suitable reagents for the following examples….

CH3-O-CH=Pph3

i.Base ii. PhSeBr iii. Oxidant (e.g. H2O2)

ph3P=CH2 OR i. Me3SiCH2MgCl ii. H+

iii. KH or HF

BF3/DMSO (solvent)

Peterson olefinating agent better than P-ylid

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MeLi(Excess)

Ph3P: /(EtO)3P:

i. Base/ii. H+/heat

Diethyl oxalate


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Organoborane and hyper-conjugation

From Boron, the alkyl group contributing less hyperconjugation effect migrates to carbonyl carbon

reagents in organic synthesis

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