Types of reaction process

Types of reaction process:

chemical synthesis: Examples of synthetic
conversions include aspirin, diazepam, ibuprofen.
biotechnology or microbial action: Examples
include antibiotics, vaccine production, blood
plasma products. This method produces the high
value products;
extraction: This can be by extraction of natural
materials from animal or plant material such as
the opium alkaloids, dioxin, heparin, insulin (pigs
pancreas), thyroxine (animal thyroid gland).
 Synthetic chemistry based processes
include
 simple liquid/liquid reactions,
 complex liquid reactions
with catalysis such as Grinards, Freidel Craft,
reaction with strong reagents such as phosphorous
oxychloride, thionyl chloride or elemental halogens such as
bromine or chlorine.
Conventional batch reactor systems temp -25°C to +
1600C, and full vacuum to 6barg
The medium used for heating & cooling
 multiple fluids steam, cooling water, refrigerant fluids
heated or cooled by indirect
single fluids heat transfer oil-
contact with steam, cooling water or refrigerant
Alternative reactor systems
Alkylation

Phenobarbital, barbital…
Carboxylation and acetylation

salicylic acid and derivatives, acetaminophen

Condensation and Cyclization

Diazepam, riboflavin, vitamin B1…

Dehydration

Ether
Halogenation

Chloroform
Oxidation
isoniazid, nicotinic acid …
Sulfonation
sulfanilamide…
Amination
propanolol
Complex chemical conversions
Vitamin C, Darvon…
 Alkylation:
 Phenobarbital,5-ethyl-5-phenylbarbituric acid, usefulness in
epilepsy.
Made from phenylethylmalonic diethyl ester, which is
condensed with urea to form the product.
 Barbital :
Diethylbarbituric acid, is sold under the trade name Veronal.
It is the oldest of the long-acting barbiturates.
Is derived through diethyl malonate.
 Carboxylation and acetylation
Aspirin
Phenol readily undergoes acetylation with acetic
anhydride in the presence of an acid catalyst such as
concentrated sulfuric acid to yield acetyl salicylic acid,
which is commonly known as aspirin.
Salicylic acid reacts with acetic anhydride in acidic
medium to give aspirin with a byproduct of acetic acid.
Carboxylation and acetylation
ex- Aspirin production
 Acetaminophen
sold under the name Tylenol, is a widely used
analgesic and antipyretic that is an OTC drug.
Combined with the codeine it is one of the top
five prescription drugs.
Prepared by treating p-aminophenol with a
mixture of glacial acetic acid and acetic
anhydride.
 Dehydration
Ether USP : is used for general anesthesia and as a
solvent.
Ether and nitrous oxide, both anesthetics, are
manufactured through dehydration reactions.
The very simple and long used manufacturing process
for ether had been the dehydration of alcohol by sulfuric
acid.
The anesthetic ether is especially purified and packaged.
ethylene.
Both USP and commercial grades are now supplied as a
by-product from the manufacture of alcohol from
Dehydration of alcohol by sulfuric acid
Eg – Ether production
 Halogenation
Generally chlorination used for synthesis of various
intermediates, such as chloride or bromide, and homologs
employed in production of BPC. Example: Chloroform
Used as an anesthetic by inhalation, but now is used only
rarely in U.S.
used as solvents for alkaloids, in chemical analysis and as
preservative during Aq. Percolation of vegetable drugs,
preventing bacterial decomposition.
Chloroform: although alcohol and chlorinated lime were
formerly used to make chloroform, it is now made from
acetone and calcium hypochlorite because the reaction is
rapid and yield is high.
Pure chloroform decomposes readily on storing. Addition
of small amount of alcohol is required to prevent
decomposition.
Chloroform- made from acetone and calcium
hypochlorite(Halogenation)
 Oxidation

Isoniazid : Isonicotinic acid hydrazide, is the most

potent and selective of the tuberculostatic antibacterial
agents.
 Nicotinic acid and Nicotinamide USP
 Nicotinic acid and Nicotinamide are known as niacin and
niacinamide in the food industry.
 Niacin is the most stable of all the vitamins and is essential to
humans and animals for growth and health.
 In the body, niacin is converted to niacinamide, which is
essential constituent of coenzymes I & II, which are involved in
the oxidation of carbohydrates.
 Added to foods to enrich color.
 Niacin and niacinamide are nutritionally equivalent
FORMATION OF NIACIN
/NIACINAMIDE
 SULFONATION
Drugs made by sulfonation are
 sulfanilamide,
 sulfadiazine,
 sulfanguanidine and
 sulfathiazole.
Sulfanilamide, the original member of this class, is a very
interesting chemical ,long known as an intermediate in
the manufacture of an orange-colored dye, Prontosil,
before its antibacterial properties were recognised.
It was ascertained in 1935 that sulfanilamide (p-
aminobenzene sulfonamide) was the active antimicrobial
part of the dye.
The sulfa drugs have been largely replaced by
antibiotics because the sulfas have relatively narrow
antibacterial spectra, comparatively low potency and
cause development of resistant organisms and many
adverse side effects in humans.
They are used as diuretics.
Sulfanilamide synthesis
 Furosemide(sulfa drug)
4-chloro-N-furfuryl-5-sulfamoyl anthranilic acid, is
prepared by treating 2,4,5-trichlorobenzoic acid, and
further treatment with ammonia and furfuryl amine. This is
a very potent diuretic and was the fifth most prescribed
medicine in 1981.

2,4,5-trichlorobenzoic
acid
 Amination
Many chemicals used as drugs contain one or more amine
groups. These may be introduced into the compound by
using ammonia or an amine.
E.g. Propanolol.HCl: sold under the name inderal, was the
most widely prescribed drug in 1981. It is used as an
antianginal and antihypertensive drug.
Propanolol is prepared from 1-napthol & epichlorohydrin.
Subsequent treatment with isopropyl amine opens the epoxy ring
to yield propanolol. Treatment with HCl yields the hydrochloride.

isopropyl
amine
 Condensation and Cyclization
Diazepam USP: is a substituted benzodiazepine made by a
complex series of reactions, one of which involves
Cyclization.
It is an anti-anxiety drug, often called a tranquilizer.
It is prepared by treating p-chloro methyl aniline with
benzoyl chloride and hydroxylamine to produce
benzophenone oxime.
Reaction of the oxime with chloroacetyl chloride in the
hydroxylamine chloroacetyl chloride
presence of NaOH and subsequent reduction yields
diazepam.
p-chloro benzoyl chloride
methyl
aniline
Complex chemical conversions(vitamin
C)