reagents in organic synthesis
TRANSCRIPT
REAGENTS IN ORGANIC SYNTHESISREAGENTS IN ORGANIC SYNTHESISMr. Anand S Burange,Institute Of Chemical Technology, Matunga , Mumbai-400019E-mail: [email protected]
HO
O
HO
H
N
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).
A B
2
3
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……
Lecture at KTHM College, Nashik on 15th September 2012
4
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.
Cl NH2NaNH2/NH3
Via Benzyne intermediate
Nu Nu
Lecture at KTHM College, Nashik on 15th September 2012
5
Cl
ClNaNH2/NH3
Cl
Cl
NaNH2/NH3
Cl
Cl
NaNH2/NH3
Cl
NH2
Cl
NH2
Cl
NH2
Lecture at KTHM College, Nashik on 15th September 2012
6
OHNH2 i. Cl-PO(OEt)2/NaH
ii. NaNH2/NH3 (Via Benzyne)
Br CH(CO2Et)2
Cl
Me Me Me
OH
OH
OMe
Cl NaNH2/NH3
OMe
NH2
i. NaNH2/NH3
ii. -CH(CO2Et)2
OH-/340o C
NaNH2/NH3
Lecture at KTHM College, Nashik on 15th September 2012
7
1,3-propan-dithiolSHSH
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.
O
HHSH SH / H+ S S
H HProtected form of formaldehyde
LDAS S
H
X
X
n S S
H
X
n
Again LDA is used to get S S
n n
Owhich on deprotection using acid/ Hg2+ yields
Lecture at KTHM College, Nashik on 15th September 2012
8
H H
OO
O
O
O
Predict alkyl halide required with 2 eq. of LDA….
BrCH2CH2Br
BrCH2CH2CH2Br
BrCH2CH2CH2CH2Br
BrCH2CH2CH2CH2CH2Br
Lecture at KTHM College, Nashik on 15th September 2012
9
Methylmethyl thiomethyl sulfoxideSMe
SMe
O
H
H
-CHO group can be introduced at a beta position of enone system can be asses by using methylmethyl thiomethyl sulphoxide
O
CHO
SMe
SMe
O
H
H
i. LDA
ii.O
iii. H3O+/Hg2+
Lecture at KTHM College, Nashik on 15th September 2012
10
Baeyer- Villiger Oxidation and migratory aptitude
R R'
O
+ RCO3HR OR'
O
Carbonyl per acid Ester
Per acid
R
O
OO
H
Electrophilic oxygen
Why electrophilic ?
R
O
OO
H
Nu-
R
O
O + Nu-OH
Stable carboxylate anion Lecture at KTHM College, Nashik on 15th September 2012
11
Various per acids used for Baeyer Villiger oxidation and epoxidation reactions
Cl
CO3H
m-Chloroperbenzoic acidm-CPBA
O
OOH
O
O 2
Mg2+
Magnesium monoperoxyphthalateMMPP
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
12
Me
O
Me
O
O
NO2
m-CPBA
m-CPBA
m-CPBA
Me O
O
Me O
O
O
O2N
O
Lecture at KTHM College, Nashik on 15th September 2012
13
Bartlett has proposed one step mechanism for epoxidation of alkene using per-acid
R
O O
O H O
Lecture at KTHM College, Nashik on 15th September 2012
14
OH
O
OH
OH
OH
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
15
Some selectivity aspects during epoxidation reactions…..
MeO
OH
OCOCH3
m-CPBA
m-CPBA
m-CPBA
m-CPBA
m-CPBAO
MeO
O
O
OH
O
OCOCH3
O
50:50 both stereo-isomers are formed
Regioselectivity:
Stereoselectivity
Lecture at KTHM College, Nashik on 15th September 2012
16
Cleavage of 1,2-diols
OH
OH
NaIO4
OR LTA
O
O
OH
OHNaIO4
No CleavageNaIO4 is selective for only cis-diol
OH
OH LTAO
OLTA breaks both cis and trans diols
I
O
O
O ONa
Sodium periodate
Pb
OAc
OAc
OAcAcO
Lead tetraacetate
Vs
Lecture at KTHM College, Nashik on 15th September 2012
17
O
O
COOH
COOH
OH
OH
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
18
DIBAL-H and Solvent-Effect
AlH
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
19
R
O
ORDIBAL-H (eq.)
-78o C, THF(polar solvent)R H
O
R
O
ORDIBAL-H (eq.)
-78o C, Hydrocarbon(nonpolar solvent)R H
O
In Polar solvent
R OR
O
AlHR OR
O
H
Al O
R OR
O
H
AlO
R H
O
Lecture at KTHM College, Nashik on 15th September 2012
20
In non-polar solvent
R OR
O
AlHR OR
O
H
Al
Stable at low temperature and recovered at -78oC
H2O
R OH
OR
H
Hemiacetal
R OH
OR
H
Hemiacetal
R H
OH3O
+
Lecture at KTHM College, Nashik on 15th September 2012
Lecture at KTHM College, Nashik on 15th September 2012 21
CO2Et
O
NaBH4EtOH
CO2Et
OH
CO2Et
O
LiAlH4
Et2O
OH
OH
CO2Et
O
1.EG/H+
2.LAH
3.H3O+
O
OH
NaBH4 Vs LAH
22
Simmons-Smith Cyclopropane SynthesisIt 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.
CH2I2 + Zn(Cu) ICH2ZnI
A carbenoid
Simplest carbene : Methylene
:CH2
Can be easily prepared by thermolysisor by irradiating diazomethane gas.
CH2
Carbene six electron containing species
H
H
Lecture at KTHM College, Nashik on 15th September 2012
23
Me
Me
Me Me
KOC(CH3)3
CHCl3
KOC(CH3)3
CHBr3
CH2I2/ Zn(Cu)
diethyl ether
Cl
Cl
Me Me
BrBr
Me Me
Lecture at KTHM College, Nashik on 15th September 2012
24
Epoxidation and cyclopropanation of alpha-beta unsaturated enone systems
O OO
O
H2O2/OH-Me2SOCH2
-
Stabilized sulphur ylid
Lecture at KTHM College, Nashik on 15th September 2012
25
Unstabilized sulphur ylids are useful to convert carbonyls to respective epoxides
R
O
R
MeS
Me CH2
R
O
R+ Me2S
Application of unstabilized sulphur ylid
Lecture at KTHM College, Nashik on 15th September 2012
26
Diazomethane for ring expansion
Diazomethane is a poisonous gas. It must be handled with great care.
CH2N2
H2C N N H2C N N
Needle like nucleophile
Structure:
Lecture at KTHM College, Nashik on 15th September 2012
27
O
O
O
H
Me
CH2N2
CH2N2
CH2N2
O
O
Me
O
Me
Epoxide is a product of side-reaction occurs during this reaction Lecture at KTHM College, Nashik on 15th September 2012
28
!!ANTI PERIPLANAR RELATIONSHIP!! / Elimination reaction
iPr
Cl
MeRO-
?
iPr
Cl
Me
H
iPr
Cl
Me
HRO-
iPr Me
Lecture at KTHM College, Nashik on 15th September 2012
29
NH2OH
OH
NH2
NH2OH
NaNO2/HCl
NaNO2/HCl
NaNO2/HCl
CHO
O
O
NaNO2 /HCl (Semi-pinacolone rearrangement)
Lecture at KTHM College, Nashik on 15th September 2012
30
O
O
O
O
CHO
O
CH2
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
CHO
31
O
OEt
O
CO2H
O
COOH COCH3
MeLi(Excess)
Ph3P: /(EtO)3P:
i. Base/ii. H+/heat
COOEt
COOEt
Diethyl oxalate
Lecture at KTHM College, Nashik on 15th September 2012
32
Lecture at KTHM College, Nashik on 15th September 2012
Organoborane and hyper-conjugation
B
Et
Me i. CO(1atm)H2O solvent
H2O2/OH-
O
B
Et
Me
C O
CarbonylationB
Et
Me C
O
B
Et
O
Me
Et
Me
BO
H2O:
B
Me
Et
OH
OH OOH
B
Me
Et
OH
OH
OHO
B
OH
OEt
OHMe
O
From Boron, the alkyl group contributing less hyperconjugation effect migrates to carbonyl carbon
33