First Year Chemistry Theory (Organic)

Starting date: 20 th October (Every Mon, Wed, Thu) Finishing Date: 17 th November Teacher: Prof. A. Basak Reference book: Clayden/T.W.G. Solomons Peter Sykes Topics to be covered: 1) Structure / stereochemistry 2) Ionic rxns– addition/ elimination/substitution/ rearrangements 3) Free radical reactions 4) Concerted reactions(Diels Alder/electrocyclic) 5) Amino acids /peptides/enzymes (chymotrypsin) 6) Carbohydrates/ nucleic acids

Lecture 1

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Why read organic chemistry?

O R 1

Life is organic chemistry Organic chemistry is the chemistry of the compounds of carbon Deoxyribonucleic acids or DNA RNA Proteins

H 2 N O N H O O Base

Drug molecules:

O P O O O H N O Base R 2 O O NHCOCH 3 OCOCH 3 R H N H H S O O

Penicillins

N COOH CH 3 CH 3

Aspirin

COOH OH

Paracetamol

H 3 C COOH

Ibuprofen

Stereochemistry:

Chemistry in space, as a function of molecular geometry.

Constitution based chemistry:

OH OH OH

All these alcohols behave differently to certain reagents. That is due to their different modes of connectivity.

A B D C X X C A D B 

x = functional group with same connectivity. However, reactivity of X may differ again certain reagents.

H OH OH

Reactivity of the hydroxyl groups somewhat different.

H

Stereoisomerism Isomerism constitutional stereo chain C - C - C - C C - C - C C functional C - O - C C - C -O Enantiomers: positional enantiomers diastereomers C - C - C O C - C - C O Stereoisomers that are mirror images of one another H 3 C CH 3 COOH HOOC H H OH OH enantiomers If a molecule is nonsuperimposable with its mirror image, then it becomes optically active and is called a chiral molecule.

Chiral Centre (Asymmetric Centre): An atom, usually carbon attached to four different ligands (atoms or groups) Stereogenic Centre: An atom, again usually carbon, in which interchanging the position of two ligands gives rise to a stereoisomer.

This includes the carbon atom attached to four different ligands as also the sp2 carbon which can show cis-trans isomerism Y X C R Z Y X C Z R Me H C C Me H Me H C

Stereogenic centre Stereogenic centre

H C Me

Representation in 2D: Projection Formula : Fischer, Newman………….

R Fischer Projection : Y X Z Suppose a molecule is drawn as : X Z Y R R X Rules: (1) Exchange in a group of three allowed Z X Y R Y Z Z R Y R R X Z Z Y X Z Y X X R Y

(2) 180 0 in plane rotation is allowed X R Y Y Z Z X R (3) 90 0 in plane rotation ?

Not Allowed (4) 180 0 out of plane rotation ?

Not Allowed

Absolute configuration : The R,S - notation (1)Assign priority sequence to the four groups attached to a stereogenic carbon following the sequence rule.

(2) Observe the stereogenic centre from a direction opposite to the group of lowest priority.

(3) Trace the path from 1 to 2 to 3 If clockwise R ( rectus, right) If anticlockwise S (sinister, left) 1 4 S R 2 3 1 3 2 4

Sequence Rules: (1)If the four atoms directly attached to the stereogenic centre are different, higher atomic number takes precedence over lower.

(3) H 3 C H (4) C S (1) Br Cl (2) (2) If the atoms directly attached to the stereocentre are same, then work outward along the two chains atom by atom until a point of difference is reached. (1) Br (4) CH 2 CH 2 CH 3 CH 2 CH CH 3 s CH 3 (3) (3) Double and triple bonds are treated by assuming that each such bonded atom is duplicated or triplicated.

O C H O C O C H

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C OH OH H CH CH 2 C C H H C H C

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C CH 3 H CH 3

What are absolute configurations of the following compounds : O H 3 CHC HC C H H C H C H 3 C HC OH H 3 C CN H 3 C Cl R H (2) More rules: H (4) Br Br C C (1) R precedes S Cl OH (3) S H S 1 Br CH 3 1 1 Br H 2 E precedes Z cis precedes trans 2 Cl Z H 2 2 Cl E CH 3 1 Isotopic discrimination to HO be applied only when atomic no. fails H C CH 2 CD 2 CH 3 CH 2 CH 2 CH 3 C CD 2 CH 2 CH 3 CH 3 CH 2 CH CH 3