The document discusses various synthetic reagents used in pharmaceutical chemistry, including aluminium isopropoxide, n-bromo succinimide (NBS), diazomethane, and n,n-dicyclohexyl carbodiimide (DCC), highlighting their molecular properties, preparation methods, and applications in chemical reactions. Key uses include the oxidation of alcohols, hydrolysis of oximes, and synthesis of peptides. Additionally, it details the preparations and reactions associated with Wilkinson's catalyst and Witting reagent in alkene synthesis.

1. Rani T. Bhagat
M . Pharmacy
(Pharmaceutical Chemistry)
1

2. 2
Introduction
Aluminium Isopropoxide
N-Bromo succinimide (NBS)
Diazomethane
N,N Dicyclohexyl Carbodimide (DCC)
Wilkinson’s Catalyst
Witting reagent

3. 3
Synthetic reagents
are those chemical
compounds used as a
catalyst in various
chemical reaction.
A suitable choice
of reagents and
reaction conditions
are essential for
the success of a
reaction for the
desired product.
Reagents have been
found that can
degrade complex
molecule to simple
known molecules
which enabled us to
elucidate the structure
of complex
compounds.

4. Structure
Properties
4
Molecular formula: C9H21O3Al
Molecular weight: 204.25g
It is white solid.
It is soluble in water.
Uses  Reduction of carbonyl compound,
 Oxidation of alcohol,
 Hydrolysis of oximes,
 Preparation of ether,
 Rearrangement of epoxide to allylic ether.

5. Preparation
• It is prepared by reacting isopropyl alcohol with amalgamated
aluminium foil in the presence of a small amount of carbon
tetrachloride as catalyst when hydrogen evolution ceases the molten
alkoxide is distilled at reduced pressure.
5

6. Applications
Hydrolysis of oximes-
Oximes can be converted into parent carbonyl compound by aluminium
isopropoxide followed by acid hydrolysis.
6
N
OH
R1 R2
Al(O-
iPr)3
HCl
O
R1 R2
Merrwein Panndorf Verley (MPV) Reduction-:
The reduction of aldehyde and ketones takes place by heating the
carbonyl compound with aluminium isopropoxide in the presence of
excess isopropyl alcohol .the alcohol reduction product is obtained from
the reaction mixtrue after acidification and acetone is generated from
isopropyl alcohol.this is called as Meerwein –ponndrof-verley reduction.

7. Oxidation of alcohols ( Oppenauer oxidation) -
Alcohol on refluxing with aluminium isopropoxide in acetone and
benzene or toluene are oxidised to aldehyde or ketone .acetone acts as
hydrogen acceptor and is converted into isopropyl alcohol .the presence
of excess of acetone derive the reaction towards the oxidation product.
7
Regio-chemoselective ring opening of epoxide-
Functionalized epoxide are regioselectively opened using aluminium
isopropoxide and 2- trimethylsiloxy azide by attack on less substituted
carbon.
O
R2
HH
R1
R2
N3
OTMS
R1CH3SiN 3
AL(OCH - CH 2)3
CH2Cl 2

8. Structure
Properties
8
Molecular formula-C4H4BrNO2
 N-Bromosuccinamide or 1-Bromo 2,5-pyrrolidenedione
 Convenient source of bromine for both radicals substitution and
electrophilic addition reaction
Molecular weight-177.98g

9. Preparation
9
NO O
H
+
Br2 + H Br
NaOH
0
o
C
Succinamide bromine NBS
N OO
Br
• N-Bromosuccinamide can be prepared from succinamide and bromine in
presence of sodium hydroxide solution, the white product obtained is washed
with water or acetic acid.

10. Applications
• Addition of alkenes –
N-Bromosuccinamide react with alkenes in aqueous solvent to give
bromohydrins.Side reaction include formation of α-bromoketones and
dibromo compound it can be minimised by use of freshly recrystallized
NBS.
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• Bromination of carbonyl derivatives-
NBS C and α-brominate carbonyl derivative via radical or acid catalyst.

11. • Hoffmann rearrangement
NBS in presence of a strong base such as DBU react with primary amide
to produce a carbamate.
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• Allylic and benzylic bromination-
NBS is allylic and benzylic bromination involve refluxing a solution. NBS
in anhydrous CCL4 with radicals initiator usually azobisisobutylonitrile
irradiation allylic and benzylic radicals intermediates formed which
proceed to form benzylic bromine this is also called as Wohl-zeigler
reactive.

12. Structure
Properties
12
It is yellow coloured.
Toxic and highly reactive gas It
Soluble in ether
Pure at room temp and used as methylating agent.
Important precursor for the generation of carbine.

13. Preparations
 The generally used method for the preparation for the preparation of
diazomethane is by the alkaline hydrolysis of N-nitrosocompound.
 N-methyl-N-nitrourathane an warming with methanolic KOH undergoes
decomposition to give diazomethane .N-methyl-N-nitrosourethane can be
prepared by the reaction of methylamine with ethyl chloroformate, followed
by treatment with HNO2.
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14. Applications
• Methylation -
Diazomethane methylated acidic hydroxyl group carboxylic acid ,
sulfonic acid, phenol and enols. eg. methylation with diazomethane are
preparation of methyl ester of cinnamic acid from cinnamic acid and anisole
from phenol.
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• Arndt –Eistert rection-
This reaction is used for converting a carboxylic acid to their methyl
ester.
• Buchner-Cartius schlotterbeck reaction-
Diazomethane react with aldehyde to form ketone.

15. Structure:
Properties:
15
N CH N
N,N Dicyclohexyl carbodiimide or DCC
Molecular formula – C13H22N2
It is white in colour
Sweetish odour , powerful dehydrating agent
It is soluble in tetrahydrofuran , acetonitrile
It is primarily used to couple amino acid during peptide
synthesis

16. Preparation
• DCC is prepared by oxidation of dicyclohexylurea with p-toulenesulfonyl
chloride in hot pyridine . It can also be prepared by heating dicyclohexlthiourea
with yellow mercuric oxide.
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NH
O
NH
Dicyclohexylurea
N CH N
+ H OH
DCC
P-CH 3C6H4SO2Cl
HOTpyridine
NH
S
NH
Dicyclohexylurea
N CH N
+ H OH
DCC
Hg2O
Hg2S+

17. Application
• Synthesis of amides from carboxylic acids and amine
Activated carboxyl group reacts with the amine to give an amide.used in
synthesis of peptides.
• Synthesis of peroxide
Peroxides can be prepared by reaction of carboxylic acid and hydrogen
peroxide in the presence of DCC.
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+ (C6H11N2)C + (C6H11NH) 2CO
DCC
R - COOH
O
NRR
2Ar-COOH + H2O2
DCC
Ar
O
O O
O
Ar
Peroxide

18. • Moffate Oxidation
Oxidation of primary and secondary alcohol to aldehyde and ketone the
oxidant used as DMSO and DCC.
• Dehydration of alcohol
Alcohol can also be dehydrated using DCC to from corresponding alkene.
18
R - OH
DCC
OMSO
R - CHO
R- CH- OH- CH 2 -R + (C6H11N2)C R- CH= CH-R + (C6H11NH) 2CO
AlkeneAlcohol DCC

19. Structure-
Properties
19
Rh
PPh3
PPh3
PPh3
Cl
Molecular formula-C54H45ClP3Rh
Molecular weight-925.22g
It is commen name of chloridotris ( triphenylphosphane) rhadium 1
It is red coloured compound
It is soluble in benzene
It is insoluble in water
It is widely used for catalyst for hydrogenation of alkene

20. Preparation
• It is obtained by treating rhodium 3 chloride hydrate with an excess of
triphenylphosphin in reflucing ethanol.
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Rhcl3(H2O)3 + 4PPh3 Rhcl(PPh)3 +OPPh3+2Hcl+2H2O
Applications
• Hydrogenation of olefins
It is also used for hydroxylation, hydroboration of alkenes.
CH2
R
Wilkinson's
catalyst CH3
R

21. It is also called as triphenylphosphoniumylide
Structure-
• Used in synthesis of alkenes from ketones and
aldehyde.
21
P
CH2
R

22. Preparation
• Prepared from phosphonium salt which is in turn prepared by
quaternization of triphenylphosphine with an alkyl halide .the alkyl
phosphonium salt is deprotonated.
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[PPh3CH2R] + C4H9 PPh3=CHR+ C4H10
Application
 Synthesis of leucotrines
 Witting reaction –It involve synthesis of alkenes from ketones
 Prepration of olefins –
Aldehyde or ketones react with witting reagent it gives olefins.

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