Guideline Qualitative Pharmaceutical Chemistry...

Masfria

Muchlisyam

Tuty Roida Pardede

Yade Metri Permata

Qualitative Pharmaceutical Chemistry

Laboratory

Faculty of Pharmacy

Universitas Sumatera Utara

Practical Book

2019

Qualitative Pharmaceutical Chemistry

Qualitative

Pharmaceutical Chemistry

Laboratory

YADE METRI PERMATA, S.Farm., M.Si., Apt.

Prof.Dr. MASFRIA, M.S., Apt.

Prof.Dr. MUCHLISYAM, M.Si., Apt.

Dra. TUTY ROIDA PARDEDE, M.Si., Apt.

Qualitative Pharmaceutical Chemistry Laboratory

Faculty of Pharmacy

University of Sumatera Utara

Medan

2019

2

Preface

This book is arranged to complement the knowledge about the identification of the

various drug and chemical compounds quickly by chemical reaction in accordance

with our experience in laboratory Qualitative Pharmaceutical Chemistry. This book

can be used as a guide for students as teaching material in Chemistry Analysis. This

book was made on the awareness that the conventional chemical identification of

medicines still needed, although there is so many progress of modern technology of

qualitative identification. If using identification technology with modern and

sophisticated tools require huge costs and a long time. It is our experience when

receiving multiple requests to identify some unknown material, but the identification

by using some chemical reaction and in a short time has been able to know the

content of the material.

Do not copy or reproduce the contents of this book

without the written permission of the author

3

CONTENTS

Preface

Contents

Experiment 1 Dry Analysis (flame test, sublimation, pyrolysis)

Experiment 2 Analysis of Cation (Ag+,Pb

+2,Hg

+2,Bi

+3,Cd

+2,Cu

+2,As

+3,Fe

+2,Fe

+3)

Experiment 3 Analysis of Cation (Al+3

, Zn+2

, Ca+2

, Ba+2

, Mg+2

,K+, Na

+, NH4

+)

Experiment 4 Analysis of Anion (Cl-, Br

-, I

-, NO2

-, NO3

-, PO4

3- ClO

-)

Experiment 5 Analysis of Anion (SO42-

,SO32-

,S2O32-

, CO3-2

, HCO3-,borat, tetraborat)

Experiment 6 Practical Test of Cation and Anion

Experiment 7 Functional Group dan Infra red Analysis

Experiment 8 C,H,O Compound Analysis

Experiment 9 C,H,O,N Compound Analysis Part I

Experiment 10 C,H,O,N Compound Analysis Part II

Experiment 11 C,H,O,N,S Compound Analysis

Experiment 12 Practical Test

4

Experiment 1

Dry Analysis

Aim:

The students can carry out cation and anion tests, sublimation tests, pyrolysis and

crystals reaction which can be used in the preliminary test analysis of certain

compounds.

DRY ANALYSIS AND CRSYTAL REACTION

include:

flame test with Ni / Cr wire, Cu wire, sublimation, pyrolysis and crystal reaction.

1. Flame test with Ni/Cr wire.

Objective: to know the specific flame colour of several cations.

How: Ni / Cr wire is cleaned by dipping the wire into concentrated HCl (in a

tube or watch glass), then burned. Performed repeatedly until the flame of the

Bunsen on the combustion wire did not provide a special flame colour. Then

the wire is moistened with concentrated HCl and dipped in the sample, so that

there is a little sample attached to the end of the wire, then burned again,

observe the flame colour.

The experiment was repeated for another sample after the wire was cleaned.

Compare the results with the theory you know.

Sample : K+, Ba

+2, Ca

+2, As

+3, Na

+ .

Compound Flame colour

K

As

Ba

Ca

Na

Purple

Grey

Greenish yellow

Red

Golden Yellow

2. Flame tests with Cu wire ( beilstein Test).

Objective: to know the flame colour of halogen / halogenide.

5

The ways: copper wire is cleaned by rubbing it using sand paper, then burned.

Performed repeatedly until the flame of the Bunsen on the combustion wire

did not provide a special flame colour. Dip the end of the wire in a sample /

sample solution, burn and observe the flame colour.

The experiment was repeated for another sample after the wire was cleaned.

Sample: Cl-, Br

-, I

-.

3. Pyrolysis Test.

Objectives: 1. To find out whether there is residual pyrolysis or not, if the

inorganic compound is burned.

2. To see the specific colour of the remaining pyrolysis of some

metal oxides.

The ways: provide a clean porcelain cup / crucible. Place a small amount of

solid sample in the saucer, heat it over the fire, first with low heat, observe and

note the color changes that occur. Then the fire is raised and burning continues

until there is no change/ there is no black color on the cup. Record the color of

the remaining pyrolysis for each sample.

Sample : NH4Cl, ZnO, Pb(CH3OO)2, Bi(NO3)3, Hg(NO3)2.

4. Sublimation Test.

Objective: to find compounds that easily sublime.

The ways : provide a sublimation ring and a clean glass objects. Place a small

amount of solid sample into the sublimation ring that has been placed above

the glass object, then close the ring with a glass object again and above it is

given cotton that has been dripped with water, and then heated with a low

heat. Observe the shape under a microscope and draw it.

Sample: H3BO3, As2O3.

5. Crystal reaction from Cations :

Zn with K2Hg(CNS)4

Ca with oxalic acid

K with picric acid

Na with picric acid

6

Experiment 2

Analysis of Cation

Aim:

The students can analyze the cations contained in a sample.

Cations Identification : Ag+, Pb

+2, Hg

+2, Bi

+3, Cd

+2, Cu

+2, As

+3, Fe

+2, Fe

+3

Students are given 1 sample that contain one of the above cations.

Stages Analysis:

1. Organoleptic Tests: Odor, Colour and Taste

2. Flame Test with Ni / Cr

3. Classification Test

a) Group 1 cation deposition reaction

b) Group 2 cation deposition reaction

4. Specific reactions

Perform a minimum specific test if the sample is suspected

Sample: Ag+

- with dilute HCl

o percipitate + dilute NH4OH

o Dilute HNO3

- percipitate + water, heat it up ,observe after cold

- with KI

o percipitate + concentrated NH4OH

o percipitate + KCN,

- with K2CrO4

- with sulfide solution

- with α.α'dipiridil

- with Ditizon

Sample: Pb2+

- with dilute HCl

7

o percipitate + dilute NH4OH

o percipitate + water, heat it up

� observe after cold

- with KI

o percipitate + water, heat it up

o percipitate + excessive KI

- with K2CrO4

- with sulfide solution.

- with dithizon reagents

Sample: Hg2+

- with sulfide solution (HCl acid atmosphere)

o + excessive sulfide solution

- with NaOH

o + NaOH excess

- with KI

o + KI excess

- with Difenyl Carbazid

- with Dithizon

Sample: Bi3+

- With sulfide solution

o + HCl dilute

- with KI

o + KI excess

- with Na2HPO4

- with Pirogallol and HNO3 dilute

- with dithizon

Sample: Cd2+

- sulfide solution

- With NH4OH

o + NH4OH excess

8

- With KCN

- With Difenylcarbazid

Sample: Cu2+


o percipitate + HNO3 heat it up

- with NH4OH

o percipitate + NH4OH excess

- with K4[Fe(CN)6]

- with KCN

- with KI

- with dithizon

Sample: As3+

- with Sulfide solution + HCl dilute

- Gutzeit test.

- With AgNO3

o Percipitate + HNO3

- With sol. Iodii

Sample: Fe2+

- Sulfide solution

- with K3[Fe(CN)6]

- with α α’ dipiridil

- with dimetilglioksim

- with o-fenantrolin

Sample: Fe3+

- with NaOH

o + NaOH excess

- Sulfide solution

- With K4[Fe(CN)6]

- with NH4CNS

9

Experiment 3

Analysis of Cation

Aim:

The students can analyze the cations contained in a sample

Identification of cations: Al+3

, Zn+2

, Ca+2

, Ba+2

, Mg+2

, K+, Na

+, NH4

+

Students are given 1 sample containing one of the above cations

Stages of analysis:

1. Organoleptic Tests: Odor, Colour and Taste

2. Flame Test with Ni / Cr


a) Group III cation deposition reactions

b) Group IV cation deposition reactions

c) Group V cation



Sample: Al3

- with NaOH

o + NaOH excess


- with Alizarin

- with Aluminon

- with dithizon

Sample: Zn2+

- with NaOH

o + NaOH excess


- with Na2HPO4

- with dithizon

10

- reaction of crystals with KHgCNS (crystal image)

Sample: Ba2 +

- with (NH4) 2CO3

o + HNO3 e

- with H2SO4 e (crystal image)

- with K2CrO4

- with meditren solution

Sample: Ca2 +

- with H2SO4 (crystal image)

- with (NH4)2(COO)2 (crystal image)

- with K4[Fe(CN)6]

- with Meditren (crystal image)

Sample: Mg2 +

- with NH4OH e

o + NH4Cl

- with (Na) 2CO3

o + NH4Cl

- with Na2HPO4 +

o + NH4Cl + NH4OH

- with Titan Yellow

o + NaOH

Sample: K +

- with Na Cobaltritrite

- with tartric acid (crystal image)

- with perchloric acid (crystal image)

- with picric acid (crystal image)

Sample: Na +

- with Zink uranyl acetate (crystal image)

11

- with picric acid (crystal image)

Sample: NH4 +

- with NaOH

o test with litmus

o test with a stirring rod dripped with HCl

- with Nessler

- with Na.cobaltinitrit

- with Tanin and AgNO3 solutions

12

Experiment 4

Analysis of Anion

Aim:

The students can analyze the anions contained in a sample.

Anion identification: Cl-, Br

-, I

-, NO2

-, NO3

-, PO4

3-, ClO

-

Students are given 1 sample containing one of the anions above.

Stages of analysis:

1. Organoleptic Test: Odor, Color and Taste

2. Flame Test with Cu


a) Anion reaction with acid addition

b) The deposition reaction with silver nitrate, barium clorida, magnesium sulfate

and other salts

c) Oxidizing properties test

d) Reducing properties test



Sample: Cl-

- with AgNO3

o + NH4OH e

o solution + HNO3 e

- with Pb.acetat

o sediment + water, heat after cold observe

- with KMnO4 + H2SO4

- test with Kanji / KI paper

Sample: Br-

- with AgNO3

o + NH4OH e

13

o + NH4OH p

- with Pb.acetat

o + water, heat, observe after cold

- with NaOCl + HCl,

o shake with CHCl3


o test with starch paper

- with K2Cr2O7 + H2SO4

Samples: I-

- with AgNO3

o + NH4OH e

o + NH4OH p

- with Pb.acetat

o + water, heat observe after cold

- with NaOCl + HCl e

o shake with CHCl3

- with KCr2O7 + H2SO4


Sample: NO2-

- with KMnO4 / H2SO4

- KI solution

- with FeSO4 / H2SO4

- with Antipirin and HCl

Samples: NO.3-

- with H2SO4 p

- with FeSO4 / H2SO4 p

- reduction with Zn / HCl

o + antipyrin and HCl

- with diphenylamine / H2SO4

- with Zn / NaOH

14

o test with tanin solution and AgNO3

Sample: PO43-

- with AgNO3

o + NH4OH e

o + HNO3 e

- with FeCl3

o + CH3COOH

o + HNO3

- with HNO3

- with BaCl2

o + HCl e

Sample: OCl-

- with KI + H + → I2 solution

o I2 release test

- with HCl e


- with Pb. acetat

15

Experiment 5

Analysis of Anions

Aim:

The students can analyze anions are present in a sample.

Identification anion: SO42-

, SO32-

, S2O32-

, CO3-2

, HCO3-, BO3

3-, B4O7

2-

Students are given one sample that you lack any of the above anions.

Stages of analysis:

1. Test organoleptic: Odor, Color and Flavor

2. Test Bright with Cu


a) The reaction by the addition of acid anion

b) Precipitation reaction with silver nitrate, barium chloride, magnesium sulphate

and other salts

c) Tests oxidant properties

d) Reductant nature test

4. Specific reaction

Make a minimum specific test if the sample allegation

Sample: SO42-

- with BaCl2

o + HCl e

o + HNO3 e

- with Hg(NO3)2

- with Pb.acetat

Sample: SO32-

- HCl e

o test with K2Cr2O7

o KIO3 starch test paper


16

- by the K2Cr2O7 + H2SO4

- with a solution of Fuchsin

Sample: S2O32-

- with a solution Iodii

- with AgNO3

- with Pb.Acetat

o preheat the sludge + water

- with NaOH + KCN, heat + HCl + FeCl3

Sample: CO32-

- HCl e

o test with stir bar that drops of Ba(OH) 2

- with BaCl2

o + HCl e

- with AgNO3

o + NHOH

o + HNO3 e

- with MgSO4

o heat

- with HgCl2

- with CaCl2

o + NH4OH

o + HCl e

Sample: CO32-

- the sample was heated

o test with whitewash

- with MgSO4

o heat

- HCl e

o test with Ba(OH)2

- with CaCl2

17

o sediment + NH4OH

o sediment + HCl e

- with HgCl2

o sediment + HCl e

- with AgNO3

o sediment + NH4OH

o sediment + HNO3 e

Sample: BO33-

- sublimation test

o crystal image

- borax esterification with CH3OH and H2SO4p

o heat

- with phenolphthalein and 1 or 2 drops of NaOH to react weakly

o + 1 drops of glycerin,

Sample: B4O72-

- Borax esterification with CH3OH and H2SO4p

o heat

- with AgNO3

o sediment + NH4OH

o sediment + CH3COOH

o heated deposition

- with BaCl2 dropwise until excess

- with phenolphthalein

o + 1 drops of glycerin

18

Experiment 6

Practical Test of Cation and Anion

Aim:

The students can analyze cations and anions are present in a sample.

Identification Cation and Anion (from experiments 2-5)

Students are given one sample containing cations and anions

Stages of analysis:

1. Test organoleptic: Odor, Color and Flavor

2. Test Bright with Ni / Cr

3. Test Bright with Cu wire


a) Cation precipitation reaction group 1

b) Cation precipitation reaction group 2

c) Cation precipitation reaction group 3

d) Group 4 cation precipitation reaction

e) Reaction cation identification group 5

f) Identification reaction with concentrated acid anion

g) Anion precipitation reaction with silver salts, magnesium, zinc and

barium

h) The oxidation reaction anion

i) The reduction reaction anion

5. Specific reaction

For specific reaction clay at 2-5 experiments.

19

Experiment 7

Functional Groups and Infrared Analysis

Aim:

- The students can analyze functional groups contained in a sample using

chemical reactions.

- The students can analyze functional groups contained in a sample using

infrared spectrophotometry method.

Cation identification: Function group

Practicum is given 1 sample containing organic compounds to be analyzed for its

functional groups.

1. Aliphatic hydroxy group

Mono Hydroxy Aliphatic

- Azo's reaction

- Esterification reactions

Poly Hydroxy Aliphatic

- Azo's reaction

- Test with Borat / can increase the acidity of Borat solution.

- Cuprifill reactions

2. Hydroxy aromatic group

Mono Hydroxy Aromatic

- Azo's reaction

- Reaction of FeCl3

- The reaction of the Marquis

Poly Hydroxy Aromatic

- Azo's reaction

- Reduction Reactions to Fehling and Ammonia Silver

3. Carboxyl group

- Test for positive carbonyl

- Esterification reactions

4. Keton group

- Reaction with Na. Nitroprussid (Rothera Legal Reaction)

20

- Iodoform reaction

5. Aldehyde group

- Schiff's reaction

- Reduction of Tollen’s reagent and Fehling

6. Amin group

- Reactions with p-DAB HCl

- Reactions with matchstick

- Indophenol reaction

- Reactions with CuSO4

7. Nitro group

- Reactions with bases of NaOH or KOH

- Reduction in acidic conditions to primary amine.

8. Sulfon group

- Oxidized to SO42-, and identified as SO42-

9. Unsaturated bond

- The reaction is added to Aqua Brom

- Reaction to KMnO4 solution (Baeyer reaction).

Cation identification: Function group

Practitioner is given 3 samples containing organic compounds to analyze the

functional group content using a spectrophotometer. Students interpret spectrum data

obtained.

Tools and materials:

- IR plate

- Mortar and pestle

- Cotton bud

- Tissue

- KBr for IR

- Acetone

- Sample

21

Procedure:

Prepare samples to be examined. The sample must be pure compound. If in solid form

it must be the result of crystallization or the results of isolation by chromatography.

The liquid sample is purified by distillation or gas chromatography.

Samples are mixed in special mortar and pestle with paste-forming compounds

(Nujol, hexachlorobutadiene, and fluorolube) or pellets. The most commonly used

pellet is KBr, because it does not provide specific absorption. Before measuring

sample absorption, measurements of absorption from the pasta or pellet maker were

measured. The aim is to reduce the absorption caused by the humidity of the

environment against the absorption of samples obtained.

Comparison of mixing samples with KBr or Nujol is 1 mg: 100 mg, or it can be said

to be 1% sample. The maximum measurement sample that still gives good results is

with a sample content of 10%.

22

INTERPRETATION OF INFRARED SPECTRUMS

-COOH 3600 – 2400 cm-1

-OH 3500 – 3200 cm-1

-NH2 3500 – 3100 cm-1

=C-H 3150 – 3050 cm-1

-C-H (alifatis) 2950 – 2875 cm-1

-COH (aldehid) 2750 cm-1

CΞC 2250 – 2100 cm-1

CΞN 2250 cm-1

C=O 1700 cm-1

C=C 1600 and 1500 cm-1

N=O 1550 – 1350 cm-1

S=O 1350 – 1050 cm-1

C-O 1300 – 1000 cm-1

CH2 1450 cm-1

CH3 1375 cm-1

C-C 1200 cm-1

C-Cl 800 cm-1

C-Br 550 cm-1

C-I 500 cm-1

23

Experiment 8

Analysis of Compounds C, H, O

Aim:

The students can analyze reactions of compounds that have elements C, H and O with

functional groups OH Aliphatic and Aromatic both monovalent and polyvalent, and

carboxylic groups and able to distinguish compounds from one another (especially

those used/ related to the pharmaceutical field), by using certain chemical reagents.

Compounds carried out by practicum include:

1. Organic compounds used in the pharmaceutical field which has elements C, H,

and O with OH Aliphatic functional groups in the form of monovalent or

polyvalent.

2. Organic compounds used in the pharmaceutical field which has elements C, H,

and O with OH functional groups in the form of monovalent or polyvalent

3. Organic compounds used in the pharmaceutical field that have C, H, and O

elements with the -COOH functional groups in the form of mono carboxylic and

poly carboxylic.

General reaction to OH aromatic:

1. AZO Reagent Reaction:

Diazo A: 0.5% sulfanylic acid solution in (30 ml 4N HCl + 70 ml water).

Diazo B: 9% NaNO2 solution in water.

How to experiment:

Add 2 drops of ethanol or a sample solution in water into the test tube, add Diazo

A and Diazo B (4: 1 or 1: 1) and 1-2 drops of NaN 2N until reacting alkaline,

shake, heat it in a water bath, it will form a color reddish yellow to red. Add 4

drops of amyl Functions C, H and O Aliphatic, shake, color not interested Amyl

Clusters of C, H and O Aliphatic functions (colorless layer) (for groups of function

groups C, H and O Aliphatic).

Try the same for glycerin, observe and record the results.

Compare the results that occur in all samples examined.

24

2. Esterification reaction (Monovalent Aliphatic)

Reactor:

Salicylic acid, benzoic acid or acetic acid.

Concentrated sulfuric acid as a catalyst.

How to experiment:

3 drops of ethanol are put into the test tube, add a little salicylic acid crystals and

1-2 drops of concentrated H2SO4, cover the mouth of the tube with wet cotton, heat

it in a water bath for 5 minutes. Lift and dilute with 1 ml of water. Smell the smell

and smell of gandapura (for ethanol and methanol).

The experiment was repeated using benzoic acid or acetic acid. Observe and note

the smell.

3. Reaction of the committee (Aliphatic polyvalent)

Reactor:

2% CuSO4 solution, 2N NaOH solution

How to experiment:

Add a little glycerin (or sample solution in water) into the test tube, add 1 solution

of CuSO4 and 2-3 drops of NaOH solution, clear blue dark solution will form.

Heat, don't form red brick deposits.

Perform the same experiment on ethanol, observe and record the results.

Compare the results that occur in all samples examined.

4. Test with Borax (Aliphatic polyvalent)

Reactor:

1% borax solution and 0.2% phenolphthalein solution in 70% ethanol.

How to experiment:

In the test tube put 1 drop of borax solution and 1 drop of phenolphthalein solution

(the solution becomes red). Add 2 drops of glycerin. Observe and record the

results.

Do the same experiment with ethanol, observe and record the results; compare

results in all samples.

5. Carletty's reaction. (Aliphatic polyvalent)

Reactor:

Oxalic acid (crystal)

Resorcin (crystal)

Concentrated H2SO4

25

How to experiment:

2 drops of glycerin free of water (or a small amount of solid sample) is placed on

the drip plate, add a little bit of oxalic acid crystals and a bit of resorsing crystals,

stir with the stirring rod, then add 1 drop of concentrated H2SO4, stir, observe and

record the results.

Perform the same experiment on ethanol, observe and record the results. Compare

results for all samples.

General reaction to the Aromatic OH group:

1. Azo reaction (same as in C, H and O Aliphatic functional groups, but red can

form in cold conditions, if shaken with amyl alcohol, generally red can be

attracted to amyl alcohol) (for OH Aromatic groups).

2. Reaction with FeCl3

On the drip plate, a small sample or solution of neutral sample in water or

ethanol is added 1 drop of FeCl3 solution, color will be formed depending on

the sample being examined (observe the color changes that occur).

3. Reaction with aqua bromine

In a test tube (or drip plate) place a small amount of the sample solution (in

water or ethanol), add aqua brom drop by drop, (observe the results of the

reaction on the addition of a little aqua bromine, and on adding aqua bromine).

4. Lieberman's reaction (reaction with concentrated NaNO2 and H2SO4).

Reagent: 1% NaNO2 solution in concentrated H2SO4 (made new)

How to: put a little sample or sample solution into the test tube, add 1-2 drops

of reagent, leave a few minutes, then dilute with a few drops of water, will

form a red color, mix with NaOH or NH4OH, the color turns blue.

5. The reaction of the Marquis:

Reagent: mix 1 part formaldehyde with 9 parts H2SO4 solid (made new).

Method: on a drip plate a small amount of solid sample is added with 1 drop

of reagent, a color will be formed.

6. Reactions with Fehling reagents (for polyvalent phenols).

In the test tube enter 2-3 drops of the sample solution in water, add 2 drops of

fehling A and 2 drops of fehling B, if necessary heat it in the water, it will

form a yellow to brick red precipitate.

26

7. Reactions with silver ammonia (for polyvalent phenols)

Reagent: 0.5 ml AgNO3 0.1N added dilute ammonia drop by drop until the

precipitate formed dissolves again.

How to: a few drops of sample in the tube are added a few drops of reagent, if

necessary, heat the water bath, a silver mirror is formed on the tube wall.

8. The reaction with floroglusin and NH4OH or NaOH (for polyvalent OH

Aromatic), fluoroglusin reagent and NaOH 0.5 N or concentrated NH4OH.

Method: 1 drop of sample solution + a little fluoroglusin crystal + a few drops

of water + 1 drop of NaOH, stir the color.

or concentrated NH4OH, stir the color.

Based on the results of the reaction above a special reaction is carried out on

OH aromatic which is examined or suspected, according to each monograph.

General properties of carboxylic acid compounds:

Generally acidic, can react with bases to form salts that are easily soluble in water.

Dignified acid 1 which has a short C chain, in the form of a liquid that is easy to mix /

dissolve in water. The longer the C chain, the harder it is to dissolve in water.

Aromatic acid is generally difficult to dissolve in water.

Many dignified acids are generally easily soluble in water.

Identification of carboxylic acid compounds.

Given the absence of a general reaction to carboxylic acids, the identification reaction

is carried out on functional groups which may be present in the carboxylic

compounds examined.

Stages of Analysis:

1. Organoleptic test (shape, smell, taste and color)

2. Test solubility (in water or in organic solvents), then apply it over a water bath.

3. Beilstein and Ni/ Cr flame tests

4. Fluorescence

5. Pyrolysis

6. Azo's reaction

7. Esterification reaction

8. The reaction of Cuprifil

9. Carletty's reaction

27

10. Borax reactions

11. Iodoform reaction

12. Fehling's reaction

13. Silver Ammonia Reaction

Subsequent examinations were carried out based on the results obtained in the above

test, in accordance with the monograph of each suspected C, H and O Clusters.

Examples of several Pharmaceutical compounds that have elements C, H and O with

OH functional groups are Aliphatic and Aromatic:

1. METHANOL (CH3OH)

2. ETHANOL (C2H5OH)

3. CHLORAL HYDRATE (CCl3-CH (OH) 2.)

4. GLYCEROL (Glycerin = propane triol: CH2 (OH) -CH (OH) -CH2OH)

5. GLICOL ETILEN. (HOCH2-CH2OH)

6. PROPILEN GLICOL (Trimethylene glycol: CH3-CHOH-CH2OH)

7. MANNITOL

8. SORBITOL

9. PHENOL

10. NIPAGIN (Methyl p hydroxy benzoate) preservative

11. NIPASOL (Propyl p hydroxy benzoate) Preservatives

12. VIOFORM (Iodochloro hydroxy quinoline) Antiamuba

13. RESORSINOL (m-dioxy benzolum) Keratolytic

14. HIDROQUINON. (p-dioxy benzolum)

15. DERMATOL (Bismuth sub gallat) Antiseptic

16. GUAIPHENESIN (GLYCERIL GUAIACOL) Expectorant

17. ACETIC ACID (Vinegar acid: CH3 - COOH)

18. ACID BENZOAT

19. SODIUM BENZOAT

20. SALICYLATE ACID

21. SODIUM SALISILATE

22. ACID ACETYL SALISILATE

23. CITRIC ACID

24. SRIUM SITRAT

25. TARTRATE ACID

28

26. POTATO HYDRAULIC TARTRATE (Cream of tartar).

27. VITAMIN C (ASCORBIC ACID)

29

Experiments 9 and 10

Analysis of Compound C, H, O and N (I and II)

Aim:

- The students can identify pharmaceutical compounds containing elements C,

H, O and N, by the reaction classification and the functional group contained

in each compound.

- The students are able to distinguish the pharmaceutical compounds containing

elements C, H, O and N with each other based on reactions that occur.

Nearly 75% of pharmaceutical compounds containing the element nitrogen

compounds derived from both natural and synthetic made paracetamol Nitogen in

pharmaceutical compounds are usually bound in the form of: a bond with the nitro

compounds into carbon compounds, as amine primary, secondary or tetsier alkaline;

as ammonium kiuarterner; aromatic amine groups, acid amide neutral zwitterion salts

such as amino acids. Compounds that have the elements C, H <O and N contained in

compounds that have pharmacological effects such as barbital, Vitamins, Antibiotics

and Anti-histamine in addition to compounds derived from nature such as alkaloids

and amino acids

General reaction

1. As Aromatic Nitro.

The principle of this method changes aromatic nitro into primary aromatic

amines.

How it works: A number of 50 mg of aromatic nitro compounds dissolved in

ethanol add 3 ml of dilute HCl, 4 ml of water and 200 mg Zn, in the water

bath heated mixture of water for 10 minutes, then add 2 drops of reagent A.

Further Diazo solution is poured into 2 ml Diazo reagent B; formed orange or

orange precipitate Example: nitrazepam.

2. Aliphatic primary amine

Reaction Sentol: Addition to Carbon Disulfides

How it works: A solution aliphatic amine compounds dissolved in ethanol and

then sprinkled with carbon disulfide as much, is heated to evaporate the excess

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CS2, the rest of adding HgCl2 solution, showed a distinctive smell of the

aliphatic primary amine Example; Amitriptyline, Cinnarizine, Ethambutol,

Methadone, Pethidine, Propranolol, Timolol and Verapamil.

3. Basa Compound Amine

Reaction Mayer; Amine base compound forms a precipitate yellowish.

How it works: basic amine compounds dissolved in the water, if insoluble

added sulfuric acid and hydrochloric acid in order to form a clear solution, and

then inserted into the test tube was added some drops of reagent Mayer then

precipitates yellowish. The reaction can also be done in the object glas. Chinin

example HCl, Coffein.

4. Aromatic Primary Amines

Diazo reaction

Ways of working ; Number 50 mg primary aromatic amine compounds

dissolved in 1 ml of HCl 3N, the solution was treated with 2 drops of Diazo A

Furthermore, the solution is poured into 2 ml of reagent Diazo B; orange or

red color formed orange precipitate positive reaction to benzocaine, Procaine

and the reaction is positive when first added in the water bath HCl and heated

water for 10 minutes prior written Diazo Diazo A and B, Klordiazopoxid

example, HCT, Oksazepam and phenacetin.

5. Secondary Amines

Flourescamine test

How it works: Compounds of amine secondary dissolved in 2 ml of HCl 3 N

cooled to 5 ° C and then added 2 ml solution of NaNO2 1%, allowed to stand

for 5 minutes, then the solution is diluted with water 5 ml and shaken twice,

each shuffling added ether 5 ml, grab ether and washed and evaporated to

dryness, the rest of the evaporation was added phenol 50 mg, briefly heated,

cooled and treated with 1 ml of H2SO4 formed in red and ar formed when

diluted with red color.

6. The imidazole compound

The reaction with sulfanilic acid terdiazotasi

How it works: nitrogen compounds having a group of imidazole dissolved in 3

N NaOH 1 ml and then added a solution of sulfanilic acid (0.5 grams of

sulfanilic acid dissolved in 70 ml of water and then reacted with HCl 6 N 6 ml

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add water to 100 ml ) and 10% NaOH at a lot of it will form a red color

Example: Paracetamol

For nitrogen compounds can also be done the following general reaction:

1 reaction Dragendorf

2 reaction Bauchardat

3 Ninhydrin reaction

4 Ortho degan reaction Phtalaldehyde / Betta- Mercaptoetanol.

5 reaction Isonitriles

6 Condensation with 1,2 naphthoquinone Sodium 4 sulfonate

7 Reaction with nitric acid.

Stages Analysis:

1. Test organoleptic (shape, smell, taste and color)

2. Test solubility (in water or in organic solvents), then uapkan over a water

bath.

3. Test flame Beilstein and Ni / Cr

4. fluorescence

5. pyrolysis

6. Public reaction

Examples of Pharmaceutical Compounds That Has Some Elements C, H, O and N

1. GLUTAMIC ACID (HOOC-CH (NH) 2- (CH2) 2-COOH)

2. MEFENAMIC ACID

3. NICOTINE ACID

4. NICOTINAMIDE

5. P-AMINO SALICYLIC ACID

6. INH, ISONIAZID

7. DIPHENHYDRAMIN HCl

8. ANTIMO

9. EPHEDRINE

10. SALBUTAMOL

11. BENZOCAIN

12. PROCAIN HCl

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13. LIDOCAIN HCl

14. PARACETAMOL

15. PHENACETIN

16. ANTIPIRIN

17. PHENYL BUTAZONE

18. CAFFEINE

19. THEOHYLLINE

20. TEOBROMIN

21. QUININE

22. QUININE HCl

23. QUININE Sulfat

24. PAPAVERIN HCl

25. KODEIN HCl

26. DEXTROMETHROPHAN HBr

27. NOSCAPIN

28. CHLORAMPHENICOL

29. CHLORAMPHENICOL Palmitat

30. CHLORAMPHENICOL Stearat

31. PHENOBARBIT

32. DIPHENILHIDANTOIN

33. STREPTOMISIN

34. TETRACYCLIN HCl

35. OKSITETRASIKLIN HCl

36. CHLOR PHENIRAMIN MALEAT

37. ANTAZOLIN HCl

38. VITAMIN B6

39. VITAMIN M

40. VITAMIN B2

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Experiment 11

Analysis of Compound C, H, ON and S

Aim :

The students can identify pharmaceutical compounds containing elements C, H, O, N

and S, based on the reaction classification and the functional group contained in each

compound.

Sulfur element of the analysis:

1. With the method lassaigne

2. Reduction with a strong reducing agent

Compounds containing elements of S can be divided into several Alignment:

1. Thiols and disulfan

2. Tio ether compound

3. sulfone compound

4. Sulfonic acid derivatives

5. Sulfonyl urea compound

6. heterocyclic compounds

Stages Analysis:

1. Test organoleptic (shape, smell, taste and color)

2. Test solubility (in water or in organic solvents), then apply it over a water bath

3. Test flame Beilstein and Ni/ Cr

4. fluorescence

5. pyrolysis

6. Public reaction

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Examples of Pharmaceutical Compounds That Has Some elements C, H, O, N and S

1. AMPISILLIN

2. AMOKSISILLIN

3. ANTALGIN

4. SULFACETAMID

5. SULFADIMIDIN

6. SULFADIAZIN

7. SULFAGUANIDIN

8. SULFAMERAZIN

9. SULFASOMIDIN

10. SULFANILAMID

11. SULFATIAZOL

12. SULFAMETOXAZOL

13. CHLORPROMAZIN HCl

14. PROMETHAZIN HCl

15. MEBHIDROLIN NAPADISYLATE

16. THIAMIN HCL (Vitamin B1)

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Experiment 12

Practical Test

Aim:

The students can identify pharmaceutical compunds containing compounds of all

elements namely C, H, O, N, and S based on functional groups and classification

analysis found in each compound.

Analysis Step:

1. Organoleptic Test (shape, smell, taste and color)

2. Solubility test (in water or organic solvent), then evaporated over the bath

3. Flame Test Beilstein and Ni/Cr

4. Fluorescence

5. Pyrolisis

6. General Reaction

7. Special reaction/ specific

The sample tested was one of all samples analyzed from experiment 8 to 11.

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Table of reaction Test Name Reagent Procedure

Liq. Bromide Liq. Bromide Sample in distilled water or diluted

HCl acid + Liq. Bromide

Liq. Iod Liq. Iod Sample + Liq. Iod

Carletty Oxalic acid

Resorchine

H2SO4

Oxalic acid + resorchine + sample

+ H2SO4

CuSO4 Distilled water

NaOH solution

CuSO4 solution

Diluted HCl acid

Sample + 2 ml distilled water, heat

on waterbath + NaOH solution +

after the tube has been cold

+CuSO4 solution + neutralize with

diluted HCl acid

Deniges Reagent: Concentrated H2SO4 +

distilled water (2:8)

KMnO4

Oxalic acid

Sample in distilled water + reagent

+ KMnO4 + Oxalic acid

King Reaction

Diazo

Reagent: Diazo A + Diazo B (4:1)

NaOH solution

Sample + reagent + alkalize using

NaOH solution, heat on waterbath

if necessary

Fehling’s

reaction

Fehling A

Fehling B

NaOH solution

Sample + Fehling A and Fehling B

in same ratio, then heat on

waterbath

Frohde

reaction

Reagent: 1% ammonium molibdate

in concentrated H2SO4

Sample + reagent

Indophenol

reaction

NaOH solution

NaOCl solution

Phenol liquid

Sample + 2 ml of distilled water,

heat on watherbath, + 2 drops of

NaOH solution + 2 ml of NaOCl

soluton and 1 drop of phenol

liquid.

Iodoform NaOH / NH4OH solution

Aqua Iod

Alkalize the sample using NaOH

or NH4OH + Aqua Iod, then heat

on the waterbath

KbrO3

reaction

H2SO4 4 N

Saturated KBrO3 solution

Sample in 4 N H2SO4 solution +

saturated KBrO3

Lieberman

reaction

Reagent: 1% NaNO2 in

concentrated H2SO4

Sample + reagent

Mandeline

reaction

Reagent: 1% ammonium vanadate

in concentrated H2SO4

Sample + reagent

Marquis

reaction

Reagent: formaline + concentrated

H2SO4 (1:9)

Sample + reagent

Murexide

reaction

KClO3

Diluted NH4OH

Diluted HCl

Sample + KClO3 + diluted HCl,

then heat on the waterbath + 1-2

drops diluted NH4OH

Parri reaction Reagent: 1% Co(NO3)2 in

methannol

Diluted NH4OH

Sample + reagent + 1-2 drops

diluted NH4OH

Roux reaction Reagent: Filtrate of Roux 1 + Roux

2 + Roux 3 (20:1:1)

Sample + reagent

Vitalli-Morin

reaction

Concentrated HNO3

Aceton

3% KOH in ethanol solution

Sample + 0.5 ml concentrated

HNO3, dry on the watherbath;

disolve the residu in aceton + 3%

KOH in ethanol.

37

REFERENCES

Auterhoff. H, Kovar. K.A., 1987. Identifikasi Obat. Translation by Sugiarso. N.C.,

publisher ITB Bandung.

Basic Test For Pharmaceutical Substance. 1986. WHO. Geneva.

Basic Test For Pharmaceutical Dosage Form. 1992. WHO. Geneva.

Clarke’s. 1986. Isolation and Identification of Drug. 2nd

edition. The Pharmaceutical

Press. London.

DepKes RI. 1979. Farmakope Indonesia. Edisi III.

Ebel. S. 1992. Obat Sintetik. Terjemahan oleh Mathilda. B.W. Gadjah Mada

University Press. Yogyakarta.

Feigl.F. 1966. Spot Test in Organic Analysis. 7th

English edition. Amsterdam.

Oxford. New York.

Fries, J & Getrost, H., (1977), “Organic Reagents for Trace Analysis”, Emerck

Darmstadt.

Shriner.R.L, Fuson. R.C, et all. 1980. The Systematic Identification of Organic

Compound. Sixth edition. John Willey & Son. New York.

The Pharmaceutical Codex. 11th

edition. The Pharmaceutical Press. University Press.

Cambridge. London.

Treadwell F. P. et al, (1952). “Analytical Chemistry”, Vol 1 ed 9, John

Wiley&Sons, Inc New York; Page:99-295.

Vogel A.I. et al. (1953). ”Text Book of Macro and Semi Micro Qualitative in

Organic Analysis”, ed 4, Longmans Group Limited, London.

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