Abridge Note on Chemistry of

Organophosphate & Carbamate

Pesticides
Chemistry of Organophosphate

• The phosphorous atom is electrophilic, owing to the depolarization of

P=O bond and partly due to the electron-withdrawing nature of para -

nitro phenyl moiety.

• This enhances its high solubility in water.

Mode of action of Organophosphate
insecticide
• The nature of the phenyl group arising from the electron-withdrawing
property of the phenyl group makes the phosphorous atom
electrophilic;

• Hence its ability to phosphorylate nucleophile such as co-enzyme A

and also, the 4-nitro phenyl moiety is a good leaving group.
Toxicology of Organophosphorous insecticides
• Mechanism of action of organophosphorous insecticides in mammals and
insects are similar.
• Poisoning action is caused by toxification of the acetycholine stearase .
• Killing in animal is due to paralysis of striated respiratory centre.
• However, the most effective antidote is to organophosphate poisoning is
atropine, which blocks acetycholine receptors of the motor end of plate of
the para sympathetic nervous system, that controls the respiratory muscle.
• Generally, organophosphorous are less toxic compare to organochlorine
insecticide. They do not persist in the environment and
• are water –soluble compare to DDT.
 Carbamate
Pesticides
(Insecticides)
Physostigmine
• Occurs naturally in calabar bean
• Physostigma venenosum
• 1st isolated in 1864;
• Structure identified in 1923
• Synthesized by Julian Percy in 1930s
• Used against glaucoma, myasthenia gravis
• No insecticidal activity because it does not penetrate
insect cuticle.
 General Structure of Carbamate
Insecticides
• Fukuto and Metcalf
• Structure-Activity Relationships of carbamates

• Uncharged N-methyl carbamates can penetrate

insect cuticle
• 5Å [0.5 nM] separate anionic from esteratic site of
insect AChE

• All insecticidal carbamates are N-methyl carbamates

• R = CH3 or H
• X = leaving group
• Usually bulky
• Alkyl
• aldicarb
• Aromatic
Physostigmene
• carbaryl
Mechanism of Action
• Resemble OPs because they
• Inhibit AChE
• Have a leaving group that is hydrolyzed in forming the AChE-carbamate
complex
• Differ from OPs because
• AChE-carbamate complex dissociates readily
• Aging does not occur
• Atropine is a more effective antidote than the oximes (e.g., 2-PAM)
 Biotransformation of Carbamates
• Insecticidal carbamates
• Are N-methyl esters
• With R = H or CH3
• X = bulky leaving group
• Activation
• Requires cleaving of leaving
group by carboxyesterase
• Alternative metabolism
• N-demethylation
• Produces formaldehyde
as byproduct
• Epoxide metabolite
• Mediated by CYP 1A1
Toxicity
• Aldicarb
• Oral LD50 in rats is 0.9 mg/kg
• Dermal LD50 in rats is 5 mg/kg
• Carbofuran
• Human oral LD50 is 11 mg/kg
• Oral LD50 in rats is 5-8 mg/kg
• Dermal LD50 in rats is 120 mg/kg
• Carbaryl
• Oral LD50 in rats is 250-350 mg/kg
• Dermal LD50 in rats is ca 2000 mg/kg
• Chronic: OPIDN-like muscle weakness
• Temporary, even with continued exposure
Methyl Isocyanate
• Properties
• Reactive
• Exothermic polymerization
• Precursor for carbamate insecticides
• Carbaryl
• Methomyl
• Aldicarb
• Carbofuran
• Bhopal, 12/3/84
• Union Carbide plant in Madya Pradesh
• Safety deficits ---> explosion
• 8,000 dead immediately
• Permanent sequelae in survivors
• Toxicities
• Pulmonary
• Reproductive Synthesis of carbaryl from carbamoyl chloride and MIC