Synthesis of Drug -2

8/2/2019 Synthesis of Drug -2

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ALDEHYDES AND KETONES


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Aldehyde

Ketone

O

C

R HR = H, alkyl, aryl

O

C

R R'

R and R' = alkyl or arylR and R' cannot be hydrogen!

STRUCTURE


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NOMENCLATURE


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Choose the longest continuous carbon chain thatcontains the carbonyl carbon

Number from the end of the chain closest to thecarbonyl carbon

Ketone ending is -one

IUPAC Nomenclature of Ketones

Do the ketonessection of Organic Nomenclatureprogram!


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CH 3

C

CH 2

CH 2CH 3

O

2-Pentanone

EXAMPLES

O

C

CH2 CH

CH3 CH2

CH2

CH3

CH3

4-Ethyl-3-hexanone


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O

CH

CH3

CH3

3-Isopropylcyclopentanone


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Common, or Trivial, Names

Name each group attached to the carbonyl

group as an alkyl group

Combine into a name, according to the pattern:

alkyl alkyl ketone

NOTE: This is not all one word!

KETONES


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CH 3

C

CH 2

CH 2CH 3

O

Methyl propyl ketone

Example of Common Names

O

CCH2 CH2

CH3 CH3

Diethyl ketone


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O

C

CH3 CH3

acetone

dimethyl ketone

A common laboratory

solvent and cleaning

agent

SPECIAL CASES

C

O

benzophenone

diphenyl ketone

C

O

CH3

acetophenone

methyl phenyl ketoneKNOW

THESE


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Choose the longest continuous carbon chain thatcontains the carbonyl carbon

Number from the end of the chain closest to the

carbonyl carbon (carbon #1!)

Aldehyde ending is -al

IUPAC Nomenclature of Aldehydes

Do the aldehydessection ofOrganic Nomenclatureprogram.


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EXAMPLES

CH3

CH2

CH2

CH2

CO

H

pentanal

CH3

CH

CH

CO

HCH3

Cl

2-chloro-3-methylbutanal

1

2

3

4

always carbon 1aldehyde group is


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O

C

H H

O

CCH

3H

O

C

CH2

HCH3

O

C

C HCH2

CH3

O

C

C HCH2

CH2

CH3

O

C

CH2

HCH2

CH2

CH2

CH3

Formaldehyde Acetaldehyde Propionaldehyde

Butyraldehyde Valeraldehyde

Caproaldehyde

1 2 3

4 5

6

Common Names of the Aldehydes

RECOGNIZE

THESE


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O

C

H H

O

C

H CH3

C

O

H

SPECIAL CASES

formaldehyde

acetaldehyde

benzaldehyde

KNOW

THESE


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C

C C C C C C H

O

Forming Common Names of Aldehydes

CHO

Cl

-chlorocaproaldehyde( -chlorohexanal )

CHO

Cl

-chlorocaproaldehyde( -chlorohexanal )

USE OF GREEK LETTERS

.

is always the end of the chain, no matter how long


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Molecular Geometry

Carbonyl group = Planar Triangle


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Common Aldehydes



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Common Ketones



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Polar Property



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Boiling Points



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Solubility in Water



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Physical Properties



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Preparing Aldehyde

1. Oxidation of primary alcohol and oxidative

cleavage of alkenes

o Primary alcohol can be oxidized to givealdehydes. The reaction is often carried out

using piridinium chlorochromate (PCC) in

dichloromethane solvent at room temperature


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2. Alkenes with at least one vinylic hydrogenundergo oxodative cleavage when treated

with ozone to yield aldehydes.

If the ozonolysis reaction is carried out on acyclic alkene, a dicarbonyl compound


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3. Carboxylic acid derivatives can be partiallyreduced to yield aldehydes

DIBAH : diisobutylaluminium hydride


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Preparing Ketones

1. Secondary alcohol are oxidized by a

variety of reagent to give ketones


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2. Ozonolysis of alkenes yield ketones if oneof the unsaturated carbon atom is

disubtitused


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3. Aryl ketones are prepared by FriedelCrafts

acylation of an aromatic ring with an acid

chloride in the presence of AlCl3 catalyst


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REACTIVITY OF THE C=O GROUP

NUCLEOPHILIC ADDITION


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O

C

.. :+-

O

C

.. :-+

THE CARBONYL GROUP

electrophilicat carbon

nucleophilicat oxygen

Nu:nucleophilesattack here

H+ or E+electrophilesadd here

GENERALIZED CHEMISTRY


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CYANOHYDRINS


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+ CN

_

R C R

O

R C R

O

CN

R C R

O

CN

+ R C R

O

CN

H

: : : :

: : :

..

..

_

_..

OH2

A cyanohydrin

Addition of CyanideBuffered to pH 6-8

In acid solution there would be little CN-,

and HCN (g) would be a problem (poison).

a cyanohydrin

:C N:


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N

N

N

N

CH3

CH3

CH2CH

2COOH

CH2CH

2COOH

CH3

CH3

Fe

C

N..

CYANIDE ION BONDS TO HEMOGLOBIN

Cyanide bonds(irreversibly) to the

site (Fe II) where

oxygen usually bonds.

CYANIDE ISIS A POISON

You die of

suffocation -

lack of oxygen.

HCN is a gas that you can easily breathe into your lungs.

..


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ORGANOMETALLICS


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+

(R-MgBr)

M_ +

H2O

H+

R M

O

C

R R

R C R

O

R

R C R

O

R

H

+ M (OH)x

: : : :

:

..

..

(R-Li)

Addition of Organometallic Reagents

ether

These reagents cannot

exist in acid solution

workup

step

alcohol

:R -

Synthesis of Alcohols


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Summary of Reactions of

Organometallics with

Carbonyl Compounds

Organometallics with ketones yield

tertiaryalcohols

Organometallics with aldehydes yield

secondaryalcohols

Organometallics with formaldehyde yieldprimaryalcohols.

Organometallics with carbon dioxide yield

carboxylic acids.

etc.

All review

to you


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OH

OHO

CCl

Cl

Cl H

OH

OH

C

O

HCl

Cl

Cl

SOME STABLE HYDRATES

chloral chloral hydrate

cyclopropanone cyclopropanonehydrate

120o expected60o required

109o expected60o required

sp2 sp3

+

these also indicate that hydrates are possible


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Oxidation of Aldehydes

and Ketones


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Aldehydes are readily oxidized to yield

carboxylic acid

Ketones are generally inert toward

oxidation

The difference is a consequence of structure: Aldehydes have a CHO proton that can

be abstracted during oxidation, but ketones

do not


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Many oxidizing agents, including KMnO4

and hot HNO3 convert aldehydes intocarboxylic acids

CrO3 in aqueous acid is a more common

choice in the laboratory.

The oxidation occurs rapidly at room

temperature and results in good yields


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In the such cases, the laboratory oxidation

of an aldehyde can be carried out using a

solution of silver oxide, Ag2O, in aqueous

ammonia, that so-called Tollens reagent


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Aldehyde oxidation occur through

intermediate 1,1-diols, or hydrates which

are formed by reversible nucleophilic

addition of water to carbonyl groups


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Ketones are inert to the most oxidizing

agents but undergo a slow cleavage reaction

when treated with hot alkaline KMnO4.

The CC bond next to the carbonyl group

is broken, and carboxylic acid are produced

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Synthesis of Drug -2