1

SALTS OF ORGANIC BASES

The salts of organic bases can be divided into two main groups:

- the aliphatic amines or heterocyclic aliphatic amines derivatives

- aromatic heterocyclic compounds.

Due to their ionic structure these compounds are easily soluble in water, opposite to free

bases.

SPECTRAL ANALYSIS OF SALTS OF ORGANIC BASES

UV

Aliphatic amines do not absorb the UV radiation. The presence of the chromophoric and

auxochromic structures in the molecule changes the ability of UV radiation absorption.

If the molecule has benzene ring as the only chromophore, in

the UV spectra we see a characteristic strand of absorption

with a maximum within 230 – 280 nm. It has an oscillatory

structure and low intensiveness – examples are amphetamine

sulphate and ephedrine hydrochloride.

Ephedrine hydrochloride

The introduction of an auxochromic group into

the benzene ring results in a bathochromic effect

and increases intensity of the absorption strands

- examples are norepinephrine hydrochloride

and orciprenaline hydrochloride.

Orcyprenaline hydrochloride

HN

CH3

CH3

OHH

H

HCl

HO

OH

HN CH3

CH3

OH

HCl

2

N

In the UV spectra, absorption of salts of heterocyclic organic bases depends on the

characteristic aromatic heterocyclic chromophore:

Structure λ max Structure λ max

Piridine

251 nm N+

255 nm

Chinoline

225 nm

270 nm

313 nm

N+

233 nm

313 nm

Isochinoline

N

217 nm

266 nm

317 nm

N+

217 nm

273 nm

331 nm

IR

The absorption of IR radiation of ammonium salts differs from absorption of adequate

amines. The characteristic absorption peaks of ammonium salts are as follows:

Structure Type of vibration Wavenumber [cm-1] R – NH3

+ ν NH asym and sym

overtones and combinatory

δ NH3+ asym

δ NH3+ sym

3200 – 2800

2700 – 2000

1620 – 1570

1550 – 1500

R – NH2+ − R ν NH asym and sym

overtones and combinatory

δ NH2+

3000 – 2800

2700 – 2250

1620 – 1570

R – NH+ − [R]2 ν NH overtones and combinatory 2700 – 2300

1H – NMR

No specific signals can be observed.

Structure Signal range [ppm]

R 0 – 5

Ar 6 – 8

Ar – OH 3 – 8

R – OH 4 – 6

COOH 9,5 – 13

NH2 0,5 – 6

CO – NH2 ; CO – NH 5 – 9

N

3

-O

N NN N+

+

-O

pH 9-10

- HClCl

-

13C – NMR

No specific signals in the 13C – NMR spectra can be observed. All the carbon atoms give

signals according to the type of the carbon which they are:

Structure Signal range [ppm]

R 0 – 50

Ar 100 – 150

COOH Over 170

PHYSICO – CHEMICAL PROPERTIES OF SALTS OF ORGANIC BASES

Appearance

The most of the salts of organic bases are in a form of white or colorless crystalline powders,

except ambroxol, procainamide, promethazine hydrochloride and dihydralazine sulfate which

may be yellowish.

Solubility

The most of the salts of organic bases are soluble in water. Solubility differs, but only

bromhexine hydrochloride and clemastine fumarate are almost insoluble in water. The most of

the salts are soluble in 96% ethanol – exception is dihydralazine sulfate – and in methylene

chloride – exceptions are ambroxol and cetirizine hydrochlorides.

QUALITATIVE ANALYSIS

I. Analysis of the ions and functional groups

1) Alkaloids

Dissolve a few milligrams of the test substance in water, add diluted hydrochloric acid to

get an acidic pH and a few drops of potassium iodobismuthate – an orange or orange-red

precipitate is formed.

2) I-order aromatic amino groups

Diazotization and condensation with phenols: Dissolve a few milligrams of the test

substance in water, achieve acidic pH using a diluted hydrochloric acid and add a few

drops of sodium nitrite solution. After a few minutes add β-naphthol solution – an

intensive orange or red color is produce, sometimes also a precipitate.

NH2

+ HNO2

HCl

- 2 H2O

N N+

Cl-

4

To a few milligrams of the test substance add a little bit of Ehrlich’s reagent – an orange

color is produced.

3) Nitrates

Nitrates react with nitrobenzene and concentrated sulphuric acid giving dinitrobenzene,

which reacts with acetone and concentrated sodium hydroxide and gives products of

characteristic violet color. NOTE – reaction should be performed on ice.

4) Bromides

Dissolve the test substance in water, filter and add diluted nitric acid to reach acidic pH.

Add a few drops of silver nitrate solution – a white or yellowish precipitate is formed. It

is sparingly soluble in diluted ammonia.

5) Chlorides

Dissolve the test substance in water, filter and add diluted nitric acid to reach acidic pH.

Add a few drops of silver nitrate solution – a white precipitate is formed, which

immediately or after few minutes may change color into dark violet. The precipitate is

soluble in diluted ammonia.

6) Citrates

Dissolve the test substance in water, add 96% sulphuric acid and potassium permanganate

solution. Heat the solution until color disappears using the water bath. Add solution of

sodium nitroprusside in diluted sulphuric acid and amidosulphonic acid. Achieve basic

pH using concentrated ammonia until the amidosulphonic acid is fully dissolved. Adding

more volume of concentrated ammonia forms an intensive violet color.

N

CH3

CH3

H

N

H

+NH2

+

N

CH3

CH3

H

OH

+

- H2O

NO2 NO2

NO2

H3C

O

CH3

NO2

N

O-

O-

H3C

OH

+ HNO3

+

+ OH-

+

[ O ]

- H2O

NO2

N

O-

O-

+

H3C

O

5

7) Phosphates

Dissolve the test substance in water, filter and add silver nitrate solution. A yellow

precipitate is formed. Its color doesn’t change while heating and it is soluble in ammonia

solution.

Mix solution of the test substance with molybden-vanadium reagent – a yellow color is

formed.

8) Sulphates

Dissolve the test substance in water, filter, add diluted hydrochloric acid and barium

chloride solution. A white precipitate is formed.

To the solution of the test substance add iodine solution. The solution turns yellow. After

addition of a few drops of zinc chloride solution the test solution becomes colorless.

9) Tartrates

A reactive hydroxyl radical is formed in the reaction of hydrogen peroxide with Fe(II)

ions. This radical reacts with tartaric acid, which undergoes dehydration to

dihydroxyfumaric acid. Dihydroxyfumaric acid reacts with Fe(II) ions in the presence of

sodium hydroxide – a violet or purple color is formed.

A tartaric acid is decomposed to glyoxylic acid by the sulphuric acid in the presence of

potassium bromide. Glyoxylic acid reacts with resorcinol and the condensation product

undergoes bromination. First, a dark blue color is formed, which after cooling and

transferring the solution into the water changes to red.

CH3

C

CH3

O

H2C

C COOH

H2C

HO

COOH

COOH

H2C

C

H2C

O

COOH

COOH

N

O-

CH C CH3

O

N

O

CH

C CH3

O

CH3

C

CH3

O[ O ]

- CO2 - 2 CO2

+ Na2[Fe(CN)5NO]

(NC)5[Fe+ 4 -

(NC)5[Fe+ 4 --

violet

OH

HOOC

COOH

OH

dihydroxyfumaric acid - violet with Fe(II)

H OH

HOOC

COOH

H OH

Fe3+

OH

HOOC

COOH

H OH

H2O2 + Fe2+

OH- + OH

.

+ OH.

- H2O

.

+ OH.

- H2O

6

II. Other non-specific reactions of salts of organic bases:

- with Dragendorff’s reagent

- with phosphoromolybdenic acid

- with Reinecke’s salt

- with iodine in potassium iodate solution

III. Specific reactions

1. Phenylethanoloamine derivatives – ephedrine hydrochloride

Dissolve the test substance in water, add a few drops of copper sulphate solution and

concentrated sodium hydroxide solution – a violet color is formed. After addition of

methylene chloride the organic phase becomes dark green and the water phase becomes

blue.

HO

OH

+

HO

O OH

+

OH

OH

- 2 H2O

HO

OH

OH

O

O

H2SO4

KBr

HSO4-

HO

OH

OH

O

O

Br

Br

Br

Br

[ O ]

+

HN

CH3

OH

CH3

H

H

+ Cu2+

+ 2 OH-

- 2 H2O2

N

CH3

CH3

O

H

N

CH3

CH3

O

H

Cu

H OH

HOOC

COOH

H OH

H2SO4

HO

O

H

H

O

OH

O- CO2

- CO

- H2O

[ O ]

glyoxylic acid

7

Oxidation of ephedrine and characterization of the products of oxidation: Ephedrine

undergoes oxidation in reactions with: potassium hexacyanoferrate, ninhydrin or sodium

iodate. The products of those reactions – bezaldehyde, acetaldehyde and methylamine –

can be identified by the following reactions: benzalehyde – gives characteristic smell;

acetaldehyde – by iodoformic reaction; methylamine – by reaction with nihydrin.

reaction with potassium hexacyanoferrate

reaction with iodine solution in an alkaline medium

reaction with ninhydrin

2. Catechol derivatives – dopamine hydrochloride, norepinephrine hydrochloride,

epinephrine tartrate

Catechol derivatives react with Fe(III) ions and give green, violet or red color. Structure

and color of catechol derivatives complexes depend on the pH of the medium.

+ CH3CHO + CH3NH2

HN

CH3

OH

CH3

H

H

COONa+ 2 NaOI + NaOH

- 2 NaI - H2O

O

O

OH

OH

+ 2

HN

CH3

OH

CH3

H

H

CHO

OH

O

OH+ CH3CHO + CH3NH2 +

O

O

OH

OH

O

O

O

H2NCH3

- H2O- H2O

O

O

NCH3

O

OH

NCH2

H2O

- HCHO

O

OH

N

O

OO

OH

NH2

O

O

OH

OH

- H2O

HN

CH3

OH

CH3

H

H

CHO

+ K3Fe(CN)6

- K3HFe(CN)6

CI3CHO

CHI3

+ CH3CHO + CH3NH2

+ 3 NaOI - 3 NaOH

+ NaOH - HCOONa

8

A nitrosodiphenol derivative is formed in an acidic medium under the influence of HNO2.

It is oxidized by ammonium molybdate to nitrodiphenol derivative, which in an alkaline

medium forms a red-colored anion. Simultaneously is formed a red-colored dopachrome.

3. Lidocaine hydrochloride

Lidocaine gives a characteristic color in the reaction with 69% nitric acid – to the test

substance add nitric acid (69%) and evaporate till dry on a water bath. Dissolve the

residue in acetone and add ethanolic solution of potassium hydroxide – a green color is

formed.

A blue-green precipitate is formed after a reaction with 10% cobalt chloride solution in

ethanol – firstly a free lidocaine must be released after a reaction with 10% sodium

hydroxide.

N

N

H3C

CH3

O

H3C

N

N

CH3

O

CH3

Co

O

OR

Fe Cl pH 2 green

O

OR

Fe

H

O

O R

pH 4,2 violet

O

OR

Fe

H

O

O

R

H

O

O

RH

pH 8,5 red

9

N

H3C CH3

H

+

NH

N

R

NH

N

R

N

H3C CH3+

NH

N

R

NH

N

R

N

H3C CH3

H

+

NH

N

R

NH

N

R

4. Phenol derivatives – fenoterol hydrobromide

Emerson’s reaction: Phenols undergo condensation in the presence of oxidizing agent –

potassium hexacyanoferrate. A quinoinoimine derivative is formed as a product of

condensation. It has dark red color and is soluble in methylene chloride.

5. Imidazoline derivatives – antazoline hydrochloride, naphazoline nitrate, oxymetazoline

hydrochloride, xylometazoline hydrochloride

Imidazolines in aqueous solution hydrolyze to acetyl derivatives of ethylenediamine,

which give a characteristic reaction with ninhydrin.

Imidazolines give a characteristic violet color with Ehrlich’s reagent.

N

N

H3C NH2

CH3

H3C O

+

HN

OH

HO

OH

OH

CH3

- K3HFe(CN)6+ K3Fe(CN)6

N

N

H3C N

CH3

H3C O

O

HO

R

NH

N

R

+ H2O H3C

NH

NH2

O

N

N

NH

2 +

N

H3C CH3

O H

H+

- H2O

10

NH

H3CO

HN

OCH3

O

O

N

H

OHH

H

H2C

H

N

H

HOH

H

CH2

H

Dissolve the test substance in methanol, add sodium nitroprusside solution and NaOH

solution. Allow to stand for 10 min and add sodium hydrocarbonate solution – a violet

color is formed.

6. Imidazole derivatives – pilocarpine hydrochloride

Dissolve the test substance in water, add a few drops of potassium dichromate, 3%

hydrogen peroxide and methylene chloride and shake – the organic layer turns violet.

7. Quinoline derivatives – quinine hydrobromidee, quinine sulphate, quinidine sulphate

Add one of the following diluted acids to the solution of the test substance: sulphuric,

acetic, tartaric, nitric, phosphoric – an intensive blue fluorescence is presented. The

fluorescence disappears after addition of HCl.

Taleioqinic reaction – dissolve the test substance in water, add bromine water and diluted

ammonia – a green color is formed.

8. Isoquinoline derivatives – papaverine hydrochloride

Koralinic reaction – dissolve the test substance in acetic acid anhydride and heat on water

bath up to 80°C. Add concentrated sulphuric acid – a bright green fluorescence is

presented.

N

N

H3CO

H

HOH

H

CH2

H

Br2 + NH4OH

2

O

O

O

H3C

H3C

N

H3CO

H3CO

OCH3

OCH3

, CH3COO-

N

H3CO

H3CO

OCH3

OCH3

CH3

+

- H2O

+

11

N

H3CO

H3CO

OCH3

OCH3

SO2OH

H2O

HN

H3CO

H3CO

OCH3

OCH3

SO3-

HNO3

HN

H3CO

H3CO

OCH3

OCH3

NO2

+

violet

colorless

+

red

R

HO

HO

SO3-

FeCl3

R

SO3-

O

Fe

O

X

R

SO3-

O

Fe

O

O

OH

-O3S

R

green

violet

Papaverine is sulfonated by the concentrated sulphuric acid and forms violet-colored

inner salt of papaverin-6’-sulphonic acid.

After transferring the mixture into the water, the solution becomes colorless and

papaverin-6’-sulphonic acid crystallizes.

After the addition of HNO3 to the mixture is formed 6’-nitropapaverine, which is red in

the presence of sulphuric acid.

After the addition of FeCl3 to the mixture is formed green color, which changes into

violet after heating.

9. Opiates – morphine sulphate, codeine phosphate, dihydrocodeine hydrotartrate

Morphine reacts with FeCl3 solution – a characteristic violet or blue color is formed.

Morphine is oxidized by potassium hexacyanoferrate to dehydromorphine. In the

presence of FeCl3 solution a green-blue color is formed.

Opiates give a characteristic violet color with the Marquis reagent.

To codeine’s salt add concentrated sulphuric acid and a few drops of FeCl3 solution, heat

on water bath – a blue color is formed. Add a few drops of concentrated nitric acid – a

color changes into red.

10. Procaine hydrochloride

To 1 ml of the test substance solution add Ehrlich’s reagent – an orange color or

precipitate is formed.

N

H3CO

H3CO

OCH3

OCH3

H2SO4

12

Dissolve a few milligrams of the test substance in water and add diluted sulphuric acid,

shake and add potassium permanganate solution – the solution becomes colorless.

11. Phenothiazines – chlorpromazine hydrochloride, promazine hydrochloride,

promethazine hydrochloride

Phenothiazine derivatives undergo oxidation by oxidizing agents (sulphuric acid, nitric

acid, periodic acid, FeCl3, CeSO4). In these reactions the free radicals are formed, which

are orange (promazine) or red (chlorpromazine and promethazine).

12. Hydrazine derivatives – dihydralazine sulphate, hydralazine hydrochloride

Hydralazines present strong reductive properties, they react with the most common

oxidizing reagents such as Fehling’s reagent, AgNO3 solution, potassium dichromate,

potassium permanganate and others.

Dissolve the test substance in water and add 1 ml of Ehrlich’s reagent – an orange color is

formed.

NH

NH

N

H2N

N

H2N

[ O ] N

N

OH

OH