REAGENTS IN ORGANIC SYNTHESIS
Mr. Anand S Burange,
Institute Of Chemical Technology,
Matunga , Mumbai-400019
E-mail: asgburange@gmail.com
Lecture at KTHM College, Nashik on 15th September 2012
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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Reagents to be covered……
Entry
Reagent
1
NaNH2/NH3
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1,3-propan-dithiol
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Methylmethyl thiomethyl sulfoxide
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OsO4, KMnO4
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NaIO4
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LTA
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m-CPBA, Hydrogen peroxide
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Ozone
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LAH/NaBH4
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DIBAL-H and solvent effect
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Diethyl oxalate
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Simmon’s Smith Vs Stabilized sulphur ylid
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Abnormal Witting
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NaNO2/HCl (Semi-pinacolone rearrangement)
Role of anti-pariplanar relationship
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Organoborane and hyperconjugation
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Pph3 or P(OEt)3 and organosilane reagent
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Diazomethane
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PhSeBr
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MeLi
Lecture at KTHM College, Nashik on 15th September 2012
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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.
Lecture at KTHM College, Nashik on 15th September 2012
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Lecture at KTHM College, Nashik on 15th September 2012
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 i. NaNH2/NH3
ii. -CH(CO2Et)2
 OH-/340o C
 NaNH2/NH3
i. Cl-PO(OEt)2/NaH
ii. NaNH2/NH3 (Via Benzyne)
Lecture at KTHM College, Nashik on 15th September 2012
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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
Lecture at KTHM College, Nashik on 15th September 2012
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Predict alkyl halide required with 2 eq. of LDA….
BrCH2CH2CH2CH2CH2Br
BrCH2CH2CH2CH2Br
BrCH2CH2Br
BrCH2CH2CH2Br
Lecture at KTHM College, Nashik on 15th September 2012
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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+
Lecture at KTHM College, Nashik on 15th September 2012
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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
Lecture at KTHM College, Nashik on 15th September 2012
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Lecture at KTHM College, Nashik on 15th September 2012
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Bartlett has proposed one step mechanism for epoxidation of alkene
using per-acid
Lecture at KTHM College, Nashik on 15th September 2012
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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
Lecture at KTHM College, Nashik on 15th September 2012
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Some selectivity aspects during epoxidation reactions…..
Stereoselectivity
50:50 both stereo-isomers are formed
Lecture at KTHM College, Nashik on 15th September 2012
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Cleavage of 1,2-diols
Vs
No Cleavage
NaIO4 is selective for only cis-diol
LTA breaks both cis and trans diols
Lecture at KTHM College, Nashik on 15th September 2012
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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.
Lecture at KTHM College, Nashik on 15th September 2012
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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
Lecture at KTHM College, Nashik on 15th September 2012
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In Polar solvent
Lecture at KTHM College, Nashik on 15th September 2012
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In non-polar solvent
H2O
Stable at low temperature and recovered at -78oC
H3O+
Lecture at KTHM College, Nashik on 15th September 2012
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NaBH4 Vs LAH
Lecture at KTHM College, Nashik on 15th September 2012
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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 thermolysis
or by irradiating diazomethane gas.
Lecture at KTHM College, Nashik on 15th September 2012
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Lecture at KTHM College, Nashik on 15th September 2012
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Epoxidation and cyclopropanation of alpha-beta unsaturated enone systems
H2O2/OH-
Me2SOCH2-
Lecture at KTHM College, Nashik on 15th September 2012
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Unstabilized sulphur ylids are useful to convert carbonyls to respective epoxides
+ Me2S
Application of unstabilized sulphur ylid
Lecture at KTHM College, Nashik on 15th September 2012
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Diazomethane for ring expansion
CH2N2
Diazomethane is a poisonous gas. It must be handled
with great care.
Structure:
Needle like nucleophile
Lecture at KTHM College, Nashik on 15th September 2012
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Epoxide is a product of side-reaction occurs during this reaction
Lecture at KTHM College, Nashik on 15th September 2012
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!!ANTI PERIPLANAR RELATIONSHIP!! /
Elimination reaction
Lecture at KTHM College, Nashik on 15th September 2012
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NaNO2/HCl (Semi-pinacolone rearrangement)
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Lecture at KTHM College, Nashik on 15th September 2012
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
Peterson olefinating agent better than P-ylid
BF3/DMSO (solvent)
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i. Base/
ii. H+/heat
Diethyl oxalate
Ph3P: /(EtO)3P:
MeLi(Excess)
Lecture at KTHM College, Nashik on 15th September 2012
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Organoborane and hyper-conjugation
From Boron, the alkyl group contributing less hyperconjugation
effect migrates to carbonyl carbon
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Lecture at KTHM College, Nashik on 15th September 2012
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