This is PDF form for basic knowledge of Pharmaceutical chemistry

1. TOPIC: SEDATIVE AND HYPNOTIC:
MAHATMA GANDHI INSTITUE OF PHARMACY,
LUCKNOW
Presented by:-
MOHHAMAD AFAQUE
Assistant Professor
Department Of Pharmaceutical Chemistry
( M. Pharm
Medicinal Chemistry)

2. Sedatives and Hypnotics:-
Sedatives:-
➢ Sedatives are central nervous system drugs that reduce
excitement, tension and produce relaxation.
Lower concentration of drugs act as sedatives.
Hypnotics:-
➢ Hypnotics are those drugs that depress the CNS and produce
sleep similar to natural sleep.
➢ Higher concentration of the same drugs may act as hypnotic.
Classification of sedatives and hypnotics:-
Sedatives and hypnotics are classified on the basis of their chemical
structure:-

3. 1. Barbiturates:- Barbiturates are further subdivided into three types a)
long acting b) short-acting c) ultra-short acting.
2. Example of barbiturates:
a) Phenobarbitone
b) Butabarbitone
c) Cyclobarbitone
Benzodiazepines: e.g.
a) Nitazepam
b) Diazepam
c) Oxazepam
d) Alprazola

4. 3. Alcohol and Aldehyde:- e.g. Paraldehyde
4. Miscellaneous:- e.g. 1.Methyprylone, 2. Glutethimide, 3. Triclofos sodium
1. Barbiturates are further subdivided into three types:-
A ) Long acting b) short-acting c) ultra-short acting.
➢ The first two are used as sedatives and hypnotics and last one used as general
anaesthesia (e.g. thiopentone)
➢ The sodium salts of barbiturates are freely soluble in water.
Structure of barbiturates:-
N
N
O
O
O
H
R1
R5
R5'

5. a) Long-acting barbiturates:-
Phenobarbitone:-
➢ Phenobarbitone is the derivatives of barbituric acid derivatives.
➢ Phenobarbitone is a long-acting barbiturates derivative.
Structure of Phenobarbitone
N
N
O
O
O
H
H
CH2CH3
1
2
3
4
5
6
Phenobarbitone
R5= CH2CH3
R5'= -C6H5
Pyrimidine
Ethyl
Phenyl group

6. IUPAC Name:- 5-ethyl-5-phenyl-2,4,6[1H,3H]-pyrimidine-trione.
Physical properties:-
➢ It is a colourless white crystalline powder.
➢ It has no odour.
➢ It is very slightly soluble in water.
➢ It is soluble in alcohol and ether and sparingly soluble in chloroform.
Chemical properties:-
➢ When phenobarbitone is dissolved in ethanol and one drop of cobalt
chloride solution and one drop of dil. Ammonia solution are added, a violet
colour is produced.

7. ➢ If phenobarbitone is dissolved in methanol and a mixture of cobalt chloride and
calcium chloride solution is added to this solution and then after mixing and
shaking, dilute sodium hydroxide solution is added, a violet-blue colour and a ppt
are produced.
Stability and storage:-
➢ It can be affected by carbon dioxide of the atmosphere store in tightly closed
containers.
Official:
1. Phenobarbitone, I.P, B.P, 2. Phenobarbitone sodium, I.P, B.P, 3.
Phenobarbitone tablets I.P, B.P

8. Brand name:-
1. Gardenal
2. Luminal
3. Somonal
4. Dormiral
Uses:-
1. It is used in the treatment of sedatives and hypnotics.
2. It is also used in the treatment of anticonvulsant.
Butobarbitone:-
➢ This compound has the same structure as barbitone but differs from it is
having a n-butyl group at 5th position.

9. Structure:-
Physical Properties:-
➢ It is a colourless or white crystalline powder.
➢ It is practically odourless
➢ It is slightly soluble in water.
➢ It is soluble in ether and freely soluble in ethanol and in chloroform.
N
N
O
O
O
H
H
CH2CH2CH2CH3
CH2CH3
5-Butyl-5-ethyl-pyrimidine-2,4,6-trione
n-butyl group at 5th position

10. Chemical properties:-
➢ If butobarbitone is dissolved in methanol and a mixture of cobalt chloride and
calcium chloride solutions is added to the solution and then after mixing and
shaking, dilute sodium hydroxide solution is added, a violet-blue colour and a
precipitate are produced.
Stability and storage:-
➢ It should be store in well closed containers.
Official:-
1. Butobarbitone, B.P
Brand Name:- 1. Neonal, 2. Butabarbital, 3. Etoval

11. Uses:-
1. It is used in sedative and hypnotic.
Cyclobarbitone:-
➢ Cyclobarbitone also known as cyclobarbital.
➢ It is a barbituric acid derivative.
Physical Properties:-`
1. Cyclobarbitone is shiny crystalline powder
2. It has bitter taste
3. It has melting point 171-174℃.
4. It is very slightly soluble in cold water, more soluble in hot water and alcohol.

12. 5. It is insoluble in chloroform and ether.
Chemical Properties:-
➢ If a small amount of the cyclobarbitone calcium is added to a mixture of
vanillin in alcohol, sulphuric acid and water, shake and allowed to stand for 5
mint, a greenish-yellow colour is formed slowly. It become dark red when it is
heated on a water bath for ten mints.
Stability and storage:-
➢ It should be store in air tight container.
Official:- 1. Cyclobarbitone calcium, B.P
Brand name
1. Sonaform, 2. Hexemal,3. Phanodorm

13. Uses:
➢ It is used as a sedative and hypnotic.
Benzodiazepine:-
➢ Benzodiazepines are a class of sedative drug, also known as tranquillizers.
➢ Benzodiazepine is a heterocyclic compounds containing two nitrogen atoms.
➢ Benzodiazepine drugs are diazepam, Nitrazepam, Alprazolam etc.
Structure of Benzodiazepine:-
N
N
R1
O
R2
benzene ring
Diazepine ring
phenyl
ring
7-membrer ring conating 2 hetero atoms name as
(diazapine)
Nitrazepam:- R1= NO2, R2= H
Diazepam:- R1= Cl, R2= CH3

14. Nitrazepam:-
➢ Nitrazepam is a benzodiazepine derivative.
➢ Benzodiazepine is obtained by the fusion of one benzene ring and one
diazepine ring which is a 7-membered ring containing two nitrogen atoms.
➢ It contains also one phenyl ring and a nitro group is substituent.
Structure of nitrazepam:-
IUPAC Name:
N
N
O2N
O
H
7-Nitro-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one

15. Physical properties:-
➢ Nitrazepam is a yellow, crystalline powder.
➢ It has no odour.
➢ It is melt at about 226℃ with decomposition.
➢ It is practically insoluble in water, slightly soluble in ethanol and ether.
Chemical Properties:-
➢ If nitrazepam is dissolved in methanol and dilute sodium hydroxide solution
is added, an intense yellow colour is produced.
➢ Nitazepam conatins a nitro group on the benzene ring, it can be reduced to
amino group and diazotized by adding HCl and sodium nitrite. After adding
sulphuric acid, it can be coupled with N-(1-naphthyl) ethylenediamine
hydrochloride to give a red colour.

16. Stability and storage:-
➢ It should be store in well closed containers.
Official:-
1. Nitrazepam, I.P, B.P
2. Nitrazepam tablets, I.P, B.P
3. Nitrazepam capsules, B.P.
Brand name:-
1. Sedamas
2. Hypnotex
3. Nirven
Uses:- 1. It is a long-acting hypnotic with good sedation.

17. Paraldehyde:-
➢ Paraldehyde is a polymer of acetaldehyde.
➢ It is a trimer and consists of three molecules of acetaldehyde.
➢ When concentrated HCl or sulphuric acid is added to acetaldehyde,
polymerization of acetaldehyde to paraldehyde formed.
Structure:-
IUPAC Name:- 2,4,6-Trimethyl-1,3,5-trioxane
O
O
O
CH3
CH3
H3C

18. Physical properties:-
➢ Paraldehyde is a transparent, colourless or pale yellow liquid.
➢ It has strong and characteristic odour.
➢ It solidified at low temperature to give a crystalline mass.
➢ It is soluble in water but less soluble in boiling water.
➢ It is miscible with ethanol, ether, chloroform and volatile oils.
Chemical properties:-
➢ If ammonical silver nitrate is added to a solution of paraldehyde and heated
on water a bath, silver is deposited as a mirror on the side of the test tube.
➢ It can be decomposed by boiling water with sulphuric acid.

19. Storage and condition:-
➢ It is easily oxidized to acetic acid, it should be store in a small, well-filled,
airtight container.
➢ It should be protected from light and store at a low temperature.
Official:-
1. Paraldehyde, I.P, B.P
2. Paraldehyde injection, B.P.
Brand name:-
1. Paraldehyde
2. Paracetaldehyde

20. Uses:-
1. It is used as a hypnotics
2. It has no analgesic and anticonvulsant action.
Glutethimide
➢ Glutethimide is a derivative of 2,6-piperidinedione.
➢ In glutethimide one ethyl group and one phenyl group are present at the third
carbon atom to give glutethimide.
Structure:-
IUPACName: 3-ethyl-3-phenyl-2,6-piperidinedione.
H
N
O
O
C6H5
C2H5

21. Physical Properties:-
➢ Glutethimide is a white powder
➢ It has colourless crystals.
➢ It melts at 86 to 89℃.
➢ It is practically insoluble in water, freely soluble in alcohol, soluble in ether
and very soluble in DCM. (Dichloromethane).
Chemical properties:-
➢ When glutethimide is dissolved in methanol and a cooled mixture of formalin
and conc. Sulphuric acid is added and heated on a water bath, the solution
becomes red and produced.

22. Stability and storage:-
➢ It should be store in well close containers and protected from light.
Official:-
1. Glutethime, B.P
Brand Name:-
1. Doriden, Elrodorm
Uses:- 1. It is used as a hypnotics.
Methyprylone:-
➢ Methyprylone is a derivative of 2, 4-piperidinedione.
Physical Properties:-
➢ It is a white, crystalline powder.

23. ➢ It has a bitter taste and a slight characteristic odour.
➢ It melts at about 76-77℃.
➢ It is soluble in water.
➢ It is soluble in alcohol, ether, benzene and chloroform.
Storage and Stability:-
➢ It should be store in well-closed containers, and protected from light.
Brand Names:-
1. Noludar
2. Noctan, 3. Dimerin.
Uses:- 1. It is used as hypnotic.