Download - 24672 435 Experimental
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Phenol may be condensed with a -keto ester(ethyl
acetoacetate) under the influence of sulphuric acid (Von
pechmann reaction ) thus resorcinol readily under goes this
condensation to give
7-hydroxy-4-methyl Coumarin . A coumarinic ester can be anintermediate in this synthesis.
OH OH
+CH
2
C2H5OCO
CO
CH3
H2SO4
Conc.
OH OH
H
CH
C2H5OCO
COH
CH3
- H2O
OH OH
CHC
CH3
- C2H5OH
+ H2O
OH OH
CHC
CH3
CO
OH
OH OC
CHC
O
CH3
- H2
O
Resorcinol Ethylacetoacetate
Coumarinic ester
7-hydroxy-4-methylcoumarin
C O
OC2H5
1
Preparation of 7-hydroxy-4-methylCoumarin
Lab
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Required:
#Resorcinol 5.5 gm.
#Ethyl acetoacetate 6.5 gm 6.4 ml.
Conc. H2SO4 50 ml# .
Procedure:
1-In 100 ml conical flask put 5.5 gm of resorcinol (0.05M )and 6.4 ml of ethyl acetoacetate then add 50 ml of H2SO4
to conical flask.
2-Heat a mixture on the water bath for 30 minutes.
3-Cool the resulting solution and stir into crushed ice 250 gm.
4-Filter the product and wash with 100 ml H2O then weight
this product.
5-Crystallization of the coumarin carried out by methanol and
then measure m.p. .
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OH O O
CH3
7-hydroxy-4-methylcoumarin
CH3I
K2CO3
O O O
CH3
7-methoxy-4-methylcoumarin
H3C
Required:
#K2CO3 2 gm.
#Acetone 10 ml.
#Coumarin 1.76 gm.
#CH3I 2ml.
Procedure:
1-In dry round bottom flask (50 ml) put 2gm of potassium
carbonate K2CO3 (anhydrous) then add 1.76gm of Coumarin
witch dissolved in 10 ml of acetone.
2-The mixture was treated with 2ml of methyl iodide CH3I.
3-The reaction was refluxed on water bath for 2 hour.
4-Cool the resulting solution and stir into crushed ice 250 gm.
5-After the reaction was completed filter the product and wash
with 100ml water.
6-Crystallization the product carried out by methanol and
then measure m.p.
3 talytecAiramuoC
talyhteMiramuoC
baL
2
baL2
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Required:
#Coumarin 1.76 gm.#Pyridine 5 ml.
#AC2O 2 ml.
Procedure:
1-In dry round bottom flask (50ml) add 1.76gm of Coumarin
was dissolved in 5 ml of pyridine then treated withacetic anhydride AC2O 2 ml.
2-The reaction was refluxed on water bath for 2 hour.
3-Cool the resulting solution and stir into crushed ice 250 gm.
4-After the reaction was completed filter the product and wash
with 100ml water.5-Crystallization the product carried out by methanol and
then measure m.p. .
OH O
CH3
O
7-hydroxy-4-methylcoumarin
C6H5C-C
pyridine
O O O
CH3
7-benzoyl-4-methylcoumarin
OC
Ph
O
Required:
4
neB
uoC
baL
2
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#Coumarin 1.76gm.
#pyridine 5ml.
#benzoyl chloride 5ml.
Procedure:
1-In dry round bottom flask (50ml) add 1.76gm of Coumarin
was dissolved in 5 ml of pyridine then add 5 ml of benzoyl
chloride.
2-The reaction was refluxed on water bath for 2 hour.
3-Cool the resulting solution and stir into crushed ice 250 gm.
4-After the reaction was completed filter the product and wash
with100ml water.
5-Crystallization the product carried out by methanol and
then measure m.p. .
Pyrazoles are readily prepared by the action of hydrazine or
substituted hydrazines on 1,3-diketones. The reaction proceeds
via ring closure of the initially formed hydrazone . Interaction
of acetylacetone with hydrazine hydrate leads to 3,5-dimethyl
pyrazole.
5
Preparation of 3,5-Dimetyl pyrazole
Lab
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Required:
#acetophenone 5.6 ml.
#phenyl hydrazine 5 ml.
Procedure:
1-In 50 ml round bottomed flask, place acetophenone 5.6 ml
and distilled phenyl hydrazine 5ml.
2-Heat the mixture on water bath at 100 for 1hour then cool
and stir until the reaction mixture solidifies.
3-Stir with 10 ml ethanol, then filter the product and wash
with ice-cold 10ml ethanol.
8
+CPh Me
O NH
N
NH
NH2
C
CH3
P
NNH
C
H2
Ph+ H
+
NH
NH2
C
CH2
Ph+
PPA
N
CH2
H
C Ph
+
NH2
+
N
CH2
HNH
2
Ph- NH3
N Ph
phenyl hydrazine acetophenone acetophenonephenylhydrazone
2-phenylindole
- H+
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4-acetophenone Phenylhydrazone is obtained as yellow
product then measure m.p. .
Procedure:
1-In conical flask add 5gm of acetophenone
phenylhydrazone
with 30ml phosphoric acid and stir the mixture at 100
For 1 hour on water bath.
2-Cool the solution, stir into ice-water 250gm and filter the
grey precipitate then wash with 100 ml cold H2O.
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Preparation of 2- Phenyl indole
baL
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3-Crystallization the product carried out by ethanol and then
measure m.p. .
The
phe
nyl-hydrazone derivatives of acyclic Ketones are readily
cyclized to indoles in the presence of zink Chloride.
}Fiscer indole synthesis }. Borsche showed that the phenyl-
hydrazone cyclohexanone undergoes a similar reaction to yield
1,2,3,4-tetrahydrocarbazole . Glacial acetic acid is used in this
case as the solvent for phenyl-hydrazone formation and also as
the cyclizing agent.
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Preparation of 1,2,3,4-Tetrahydrocarbazole
baL
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Required:
#cyclohexanone (4.75gm; 5ml. (
#phenyl hydrazine ( 5.4gm; 4.5ml.(
#glacial acetic acid 30ml.
Procedure:
1-In 100ml round bottomed flask, add cyclohexanone 5ml in
glacial acetic acid 30ml and 4.5ml of phenyl hydrazine.
2-Heat the mixture under reflux for 10 minutes then cool
and filter the brown product and wash with100ml cold
H2O.
3-Crystallization the product carried out by 50% aqueous
ethanol and then measure m.p. .
11
Note
NH
NH
H
phenyl hydrazine cyclohexanon
+
-
O
+N N H
OH
H - H2O
N N H
H
+ H+
N NH2
H+
AcOH
NNH
2
H
+
+
N
HNH
2
H
N
H
- NH3- H
1
2
3
4
1,2,3,4-tetrah dro carbazol
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Tetrahydro carbazole must not be dried in an oven , since it is
readily oxidized to the hydroperoxide.
Benzil , hexamine and ammonium acetate react in acetic acid to
yield 4,5 diphenyl imidazole.
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Preparation of 4,5- Diphenylimidazole
+6H2O 6CH2O + 4NH3
N
CH2
N
N
CH2
N
CH2
Hexamine
baL
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Required:
benzil 2.1gm . # hexamine 0.26gm# .
ammonium acetate 6 gm . #glacial acetic acid 50ml# .
Procedure:
1-In 100ml round bottomed flask, heat a solution of 2.1 gmbenzil , 0.26 gm of hexamine and ammonium acetate 6 gm
in glacial acetic acid 50ml under reflux for 1 hour.
2-Add the resulting solution to 400ml water and remove any
turbidity that may develop followed by adding small amount
of carbon and then filtration.
3-precipitate the product by concentrated with 70ml NH4OH
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with cooling , then filter and wash with 50ml H2O.
4-Crystallization the product carried out by 10ml pyridine
and 10ml hot H2O then measure m.p. .
5-isoxazolones are prepared by the action of hydroxylamine
hydrochloride on -keto esters. Initial reaction of the
hydroxylamine with the ketone group yield an oxime which
then cyclizes to the 5-isoxazolones . Interaction of ethyl
benzoyl - acetate with hydroxylamine hydrochloride yield 3-
phenyl-
5-isoxazolone .
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Preparation of 3-phenyl-5-isoxazolone
baL
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Required:
#ethyl benzoyl acetate ( 9.6gm ; 8.5ml. (
#hydroxylamine hydrochloride 3.5gm.
#ethanol 20ml.
Procedure:
1-In 100ml round bottomed flask, add a solution of 8.5ml ethyl
benzoyl acetate in 30ml ethanol and 3.5gm hydroxylamine
hydrochloride NH2OH.HCl, 5gm sodium acetate in 12ml
H2O.
2-Heat the mixture under reflux for 2 hour then allow to cool
and filter the product.
3-Crystallization the product carried out by ethanol and
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CH2
C
OEt
Cph
O
+HNHOH CH2
CO
OEt
C ph
NHOH
OH
CH2
C
OH
Cph
NOH+H2O
-EtOH
CH2
CO
OEt
Cph
NOH
-H2O
-H2O
CH2
CO
Cph
N
O
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then measure m.p. .
Condensation of ethyl acetoacetate and it's derivatives with
various phenyl-hydrazines gives rise to the corresponding
phenyl-hydrazones , which yield pyrazolones on cyclization .Interaction of ethyl acetoacetate and phenyl-hydrazine lead
directly to 3-Methyl-1-Phenyl-5-Pyrazolone .
16
erPzaryP
CH2C
O
CH3
C
+HHN
NH
CH2C
O
H3C
CHO
HN
baL
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Required:
#ethyl acetoacetate (6.5gm ; 6.35 ml. (
#phenyl-hydrazine(4.4gm ; 4.9 ml. (
Procedure:
1-In 100ml round bottomed flask, heat a mixture of 6.35ml
ethyl acetoacetate and distilled 4.9ml of phenyl-hydrazine at
120
on oil bath for 1 hour.
2-Cool the resulting red oil and stir with 50ml ether until
solidification occurs , then filter the product and wash
with 20ml ether.
3-Crystallization the product carried out by 50% aqueous
ethanol and then measure m.p. .
17
EtO phOEt
NH
ph
CH2C
N
N
C
CH3
h
O
-H2OCH2C
N
NH
C
ph
OHO
-H2O
+H2O
CH3
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Diazotization of -phenylene diamine in dilute acid solution
yields benzo-triazole . The reaction proceeds via the mono-
diazonium salt , which then couples with the adjacent amino
-group to give the internal diazoamino compound ,
benzotriazole.
18
Preparation of Benzotriazole
NH2
NH2
NHO2
AcOH
N2
NH2
N
NN
|H
Lab1
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References:
Practical heterocyclic Chemistry by: F:Tion Smalley#.
#A text-book of Practical organic chemistry including
qualitative organic analysis (Vogel) Third edition.
**********************************
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