Induces Approximation

Overview
• Reacting molecules bring close together at binding site - weak
force

• Increase the rate of reactions

• Enzyme also behave similarly

• Boric acid assisted formation of o-hydroxymethylphenol

• Hydrolysis of chloroethanol

• Hydrolysis of phenyl salicylate

• Hydration of Pyridine-aldehyde

• Hydrolysis of p-nitrophenyl ester of Leucine

• Morpholine assisted hydrolysis of o-formylbenzoate

Formation of o-Hydroxymethylphenol

• Borate can reversibly form covalent adducts with hydroxylic -

fast reaction

• Form complex of phenol, borate and formaldehyde

 Formation of o-Hydroxymethylphenol
• Alternative mechanism - addition to the free carbonyl compound

• Also works well with metal hydroxide e.g. Cu(OH)2

• Does not work in water

 Hydrolysis of Chloroethanol*

• Hydrolysis of chloroethanol in wet dimethylformamide

• Without catalyst - cyclization into ethylene oxide

• Boron quinoline - specific catalyst, trans- product!!

• Direct attack of oxygen to C (with chloride)

 Hydrolysis of Chloroethanol*
• No cyclization product and no cis- conformation

• Override double displacement reaction -

displacement by nitrogen followed by water
 Hydrolysis of Phenylsalicylate

• Borate catalyses in basic condition

• k1 / k2 > 100 times

• Eliminate the formation of borate complex

Hydrolysis of Phenylsalicylate

• Borate readily binding with acetoacetate

• Hydroxyl group is important

 Hydrolysis of Phenylsalicylate
• Stabilize the transition state - tetrahedral addition intermediate

• In pH dependence - water and hydroxide involve

 Hydrolysis of Phenylsalicylate
• Alternative: as intramolecular nucleophilic catalyst
 Hydration of Pyridine Aldehyde

• Metal ion (Zn2+) for stabilizing the interaction

• Model for the enzyme carbonic anhydrase for the hydration

of aldehyde

• k2 >> k1 (6.5 x 106 times faster)

Hydration of Pyridine Aldehyde

• Position factor

• k3 < k2 (~300 times slower)

• Nitrogen provide reaction center

 Hydration of Pyridine Aldehyde
• Attack of water in hydration shell of the zinc ion on the aldehyde
Hydration of Pyridine Aldehyde
• Polarization of the carbonyl group by metal ion
Hydrolysis of p-Nitrophenyl Ester of Leucine

• 10-3 - 10-4 M benzaldehyde catalyze the hydrolysis

• k2 > k1 benzaldehyde is a weak base and poor nucleophile

Hydrolysis of p-Nitrophenyl Ester of Leucine

• Addition of benzaldehyde to amino to form amino alcohol

• Act as intramolecular and highly reactive nucleophile

Hydrolysis of o-Formylbenzoate Ester

• Morpholine assist the hydrolysis - similarly to hydroxide ion

 Hydrolysis of o-Formylbenzoate Ester

• Accumulation of the intermediate morpholine addition -

spectrophotometer analysis

• Undergoes decomposition by pH-independence and base catalyzed

Hydrolysis of o-Formylbenzoate Ester

• Alkaline hydrolysis may be in similar mechanism

• k2 > k3 (~2.5 x 105 times)

 Summary of Induced Approximation

• Catalyst binds with weak force ‣ Hydration of Pyridine-aldehyde

- presence of catalyst, position
• Mimicking enzymes
‣ Hydrolysis of p-nitrophenyl
ester of Leucine - different
• Induced approximation factors catalyst, concentration
‣ Boric acid assisted formation of ‣ Morpholine assisted hydrolysis
o-hydroxymethylphenol - of o-formyl benzoate - presence
presence of catalyst, different of different catalysts, position
catalyst, mimic intermediate
‣ Hydrolysis of phenyl salicylate -
functional groups, condition
(pH)
Anchimeric vs Induced Approximation