Lab 1

Preparation of 7-hydroxy-4-methyl Coumarin

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 hydroxy-4-methyl Coumarin . A coumarinic ester can be an -7 . intermediate in this synthesis

HO

OH +

C2H5OCO O C CH2 H2SO4 Conc.

HO

OH

C2H5OCO CH C CH3 - H2O

CH3

H HO

Resorcinol

Ethylacetoacetate

HO

OH HO

OC2H5

C O CH

HO - C2H5OH + H2O

OH C CH3

C O CH

- H2O

C CH3 C CH O

HO

O C

Coumarinic ester

CH3

7-hydroxy-4-methylcoumarin

: Required
.Resorcinol 5.5 gm # . Ethyl acetoacetate 6.5 gm 6.4 ml # # . Conc. H2SO4 50 ml

: Procedure
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 . Heat a mixture on the water bath for 30 minutes -2 .Cool the resulting solution and stir into crushed ice 250 gm -3 Filter the product and wash with 100 ml H2O then weight -4 . this product Crystallization of the coumarin carried out by methanol and -5 . .then measure m.p -1

baL 2

oitalyhteM niramuoC
HO O O CH3I K2CO3 H3CO O O

CH3

CH3

7-hydroxy-4-methylcoumarin

7-methoxy-4-methylcoumarin

: Required
. K2CO3 2 gm # . Acetone 10 ml # . Coumarin 1.76 gm # . CH3I 2ml #

: Procedure
In dry round bottom flask (50 ml) put 2gm of potassium -1 carbonate K2CO3 (anhydrous) then add 1.76gm of Coumarin . witch dissolved in 10 ml of acetone . The mixture was treated with 2ml of methyl iodide CH3I -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 -5 . with 100ml water Crystallization the product carried out by methanol and -6 .then measure m.p baL 2
3

oitalytecA niramuoC

: Required
. Coumarin 1.76 gm # .Pyridine 5 ml # . AC2O 2 ml #

: Procedure
In dry round bottom flask (50ml) add 1.76gm of Coumarin -1 was dissolved in 5 ml of pyridine then treated with . acetic anhydride AC2O 2 ml . The reaction was refluxed on water bath for 2 hour -2 .Cool the resulting solution and stir into crushed ice 250 gm -3 After the reaction was completed filter the product and wash -4 . with 100ml water Crystallization the product carried out by methanol and -5 . .then measure m.p baL 2

ozneB muoC
HO O O O C6H5C-C pyridine Ph C O CH3 O O O

CH3

7-hydroxy-4-methylcoumarin

7-benzoyl-4-methylcoumarin

: Required
4

. Coumarin 1.76gm # . pyridine 5ml # . benzoyl chloride 5ml #

: Procedure
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 . The reaction was refluxed on water bath for 2 hour -2 .Cool the resulting solution and stir into crushed ice 250 gm -3 After the reaction was completed filter the product and wash -4 . with100ml water Crystallization the product carried out by methanol and -5 . .then measure m.p -1

Lab 3

Preparation of 3,5-Dimetyl pyrazole

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

H H C Me C C

Me O O

H C Me C OH C

Me O

H2N NH2

keto-form

acetylacetone

enol-form
Me N

hydrazine
H C Me C OH C HN OH NH2

Me

N H

- 2H2O

Me

3,5-dimethylpyrazol

: Required
(acetylacetone (10gm ; 10.2ml # .hydrazine hydrate 5 ml # .ethanol 40 ml # .diethyl ether 30 ml #

: Procedure
In dry 150 ml round bottomed flask dissolve 10.2 ml -1 . acetylacetone and 5ml hydrazine hydrate in 40 ml ethanol stir the mixture at room temperature for 10 minutes -2 . and then heat under reflux for 0.5 hour . pour the mixture into 100 ml saturated solution of NaCl -3
6

Transfer into a separating funnel and extract the oily yellow -4 . product with 60 ml diethyl ether Combine the extracts, dry with MgSO4 and evaporate the .ether to obtain the yellow product and then measure m.p -5

Lab 4

Preparation of Acetophenone Phenylhydrazone

Acetophenone Phenylhydrazone readily undergoes the Fischer indole reaction to give 2- phenyl indole. Poly phosphoric acid (PPA) can be used advantageously as the cyclizing agent in .place of zinc chloride

H3C N H NH2

+ Ph

C Me O N H

C N

Ph

phenyl hydrazine
H
+

acetophenone
H2C

acetophenone phenylhydrazone
C
+

CH2 N C Ph H NH + 2

PPA N H

Ph

H2C +H
+

C NH

Ph

NH2

N H

-H

CH2 Ph N NH2 H

- NH3

N H

Ph

2-phenylindole

: Required
.acetophenone 5.6 ml # .phenyl hydrazine 5 ml #

: Procedure
In 50 ml round bottomed flask, place acetophenone 5.6 ml . and distilled phenyl hydrazine 5ml Heat the mixture on water bath at 100 for 1hour then cool . and stir until the reaction mixture solidifies Stir with 10 ml ethanol, then filter the product and wash . with ice-cold 10ml ethanol -3 -2 -1

acetophenone Phenylhydrazone is obtained as yellow . .product then measure m.p

-4

baL 5

Preparation of 2- Phenyl indole

: Procedure
In conical flask add 5gm of acetophenone -1 phenylhydrazone

with 30ml phosphoric acid and stir the mixture at 100 -2

. For 1 hour on water bath Cool the solution, stir into ice-water 250gm and filter the . grey precipitate then wash with 100 ml cold H2O

Crystallization the product carried out by ethanol and then . .measure m.p

-3

baL 6

Preparation of 1,2,3,4-Tetrahydro carbazole

nyl-hydrazone derivatives of acyclic Ketones are readily . cyclized to indoles in the presence of zink Chloride

The phe

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

10

H NH N H

+
O

OH N N H H

- H 2O

phenyl hydrazine
H

cyclohexanon

AcOH N H NH2
+

+H N NH2 + H

N N H H

H - H+ - NH3 N H NH2 N H

4 3 2 1

: ed

Requir

. (cyclohexanone (4.75gm; 5ml # .(phenyl hydrazine ( 5.4gm; 4.5ml # . glacial acetic acid 30ml #

1,2,3,4-tetrahydro carbazole

: Procedure
In 100ml round bottomed flask, add cyclohexanone 5ml in . glacial acetic acid 30ml and 4.5ml of phenyl hydrazine Heat the mixture under reflux for 10 minutes then cool -2 and filter the brown product and wash with100ml cold . H2O Crystallization the product carried out by 50% aqueous . .ethanol and then measure m.p -3 -1

Note
11

Tetrahydro carbazole must not be dried in an oven , since it is . readily oxidized to the hydroperoxide

baL 7

Preparation of 4,5- Diphenyl imidazole

Benzil , hexamine and ammonium acetate react in acetic acid to . yield 4,5 diphenyl imidazole
N CH2 N2O 6CH2O 6H CH2 CH2 N + 4NH3 +

Hexamine

12

: Required
# . benzil 2.1gm . # . ammonium acetate 6 gm . # hexamine 0.26gm #glacial acetic acid 50ml

: Procedure
In 100ml round bottomed flask, heat a solution of 2.1 gm benzil , 0.26 gm of hexamine and ammonium acetate 6 gm . in glacial acetic acid 50ml under reflux for 1 hour Add the resulting solution to 400ml water and remove any turbidity that may develop followed by adding small amount . of carbon and then filtration precipitate the product by concentrated with 70ml NH4OH -3
13

-1

-2

. with cooling , then filter and wash with 50ml H2O Crystallization the product carried out by 10ml pyridine . .and 10ml hot H2O then measure m.p -4

baL 8

Preparation of 3-phenyl-5isoxazolone

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 3phenyl5-isoxazolone .

14

CH2 O C OEt

C ph O

HNHOH + O

CH2 C

C ph OH OEt NHOH

CH2 O C OH

Cph NOH H2O+ EtOHO

CH2 C OEt

Cph NOH

H2O-

CH2 H2OO C O

C ph N

: Required
. (ethyl benzoyl acetate ( 9.6gm ; 8.5ml # . hydroxylamine hydrochloride 3.5gm # . ethanol 20ml #

: Procedure
In 100ml round bottomed flask, add a solution of 8.5ml ethyl -1 benzoyl acetate in 30ml ethanol and 3.5gm hydroxylamine hydrochloride NH2OH.HCl, 5gm sodium acetate in 12ml .H2O Heat the mixture under reflux for 2 hour then allow to cool . and filter the product -2

Crystallization the product carried out by ethanol and -3

15

. .then measure m.p

baL 9

aperP lozaryP
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 .

CH3 C O CH2 C + H HN NH H3C HO HN 16 C CH2 C O

Et O

ph NH ph

OEt

CH3

C N N ph

CH2 C O

H2O-

CH3

C N NH HO ph

CH2 C O

H2OH2O+

: Required
. (ethyl acetoacetate (6.5gm ; 6.35 ml # . (phenyl-hydrazine(4.4gm ; 4.9 ml #

: Procedure
In 100ml round bottomed flask, heat a mixture of 6.35ml -1 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 Crystallization the product carried out by 50% aqueous . .ethanol and then measure m.p
17

-3

Lab1 0

Preparation of Benzotriazole
Diazotization of -phenylene diamine in dilute acid solution yields benzo-triazole . The reaction proceeds via the monodiazonium salt , which then couples with the adjacent amino -group to give the internal diazoamino compound , .benzotriazole
NH2 NHO2 AcOH NH2 N2 N NH2 N | H N

18

: Required
. -phenylene diamine 5.4gm # . glacial acetic acid 12ml # . sodium nitrite 3.5gm #

: Procedure
In 250 ml beaker add 5.4gm of -phenylene diamine in -1 a mixture of 12ml glacial acetic acid and 25ml of H2O then add in a another beaker solution of 3.5gm sodium . nitrite in 10ml H2O and then mix 2 beaker together Cool the resulting solution in ice-bath and neutralize to -2 .pH = 7 by adding 2N ammonium hydroxide Stir the mixture until the product is obtained then filter and . wash the brown product with 100ml ice H2O . .Dry the product and then measure m.p -4 -3

19

: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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