Transcript 8fd26191dcc2fe1x

Pharmacy Student
Classification
1. Monohalogen Derivatives :
The halogen derivatives containing one halogen atom in a molecule
General formula CnH2n+1X
e.g. methyl Chloride CH3 Cl
2. Dihalogen Derivatives :
The halogen derivatives containing two halogen atom in a molecule
General formula CnH2n X2
e.g. Methylene Chloride CH2 Cl2
Ethylene Chloride CH2 Br – CH2 Br
Classification
3. Trihalogen Derivatives :
The halogen derivatives containing three halogen atom in a molecule
e.g. Trichloro methane
CH Cl3
4. Tetrahalogen Derivatives :
The halogen derivatives containing two halogen atom in a
molecule
Carbon Tetrafluoride
e.g. Carbon Tetrachloride
C F4
C Cl4
1. Alkyl mono halides :
General molecular formula
Cn H2n+1 X
 CH3 – Cl
 C2H5 – Cl
What Is an Alkyl Halide
 An organic compound containing at least one carbon-halogen
bond (C-X)
X (F, Cl, Br, I) replaces H
It can contain many C-X bonds
Properties and some uses
Fire-resistant solvents
Refrigerants
Pharmaceuticals and precursors
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Alkyl Halides
R-X
(X = F, Cl, Br, I)
Classification of alkyl halides according to the class of the
carbon that the halogen is attached to.
RCH2-X
1o
R2CH-X
R3C-X
2o
3o
Alkyl Halides
• Alkyl halides are organic molecules containing a halogen atom
bonded to an sp3 hybridized carbon atom.
• Alkyl halides are classified as primary (1°), secondary (2°), or tertiary
(3°), depending on the number of carbons bonded to the carbon with
the halogen atom.
• The halogen atom in halides is often denoted by the symbol “X”.
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2-Naming Alkyl Halides
Find longest chain, name it as parent chain
(Contains double or triple bond if present)
Number from end nearest any substituent (alkyl or
halogen)
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3-Isomerism in alkyl halides
 1-Position isomerism:
 Compounds having the same molecular formula but differ
in the position of the halogen atom
 C4H9Br → CH3CH2CH2CH2Br
1-bromobutane
 CH3CHCH2CH3
2-bromobutane
Br
2- Chain isomerism
 Depends on the type of the carbon chain;
 Straight or Branched.
 CH3CHCH2 Br
iso-butylbromide
CH3
 CH3CH2CH2CH2Br
1-bromobutane
3- Optical Isomerism
 Present in alkyl halides of asymmetrical carbon atom

H

CH3
CH3
Cl
CH2CH3
Cl
H
CH2CH3
4-Methods Of Preparation
 1-From Alcohol: by the action of HX, SOCl2
(thionyl chloride) or PCl5 :
 C2H5-OH +HCl
ZnCl2
 CH3(OH)CHCH3 + SOCl2
Isopropanol
C2H5Cl + H2O
C5H5N
CH3(Cl)CHCH3 +
isopropyl chloride
SO2 + HCl
 CH3OH + PCl5
CH3Cl + POCl3 + HCl
phosphorous oxychloride
2-From Alkene:
CH3CH
CH2 + HBr
CH3CHBrCH3
isoppropyl bromide
3- Halogenation of Alkanes
RH + X2  RX + HX
 explosive for F2
 exothermic for Cl2 and Br2
 endothermic for I2
Chlorination of Methane
carried out at high temperature (400 °C)
 CH4 + Cl2  CH3Cl + HCl
 CH3Cl + Cl2  CH2Cl2 + HCl
 CH2Cl2 + Cl2  CHCl3 + HCl
 CHCl3 + Cl2  CCl4 + HCl
Physical Properties
• Alkyl halides are weak polar molecules. They exhibit dipole-dipole
interactions because of their polar C—X bond, but because the
rest of the molecule contains only C—C and C—H bonds, they are
incapable of intermolecular hydrogen bonding.
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Chemical Reaction
REACTIONS OF ALKYL HALIDES
Alkyl halides (R-X) undergo two types of reactions :
substitution reactions and elimination reactions.
In a substitution reaction, the X group in R-X is
replaced by a different group, e.g. R-XR-OH +XӨ
In an elimination reaction, the elements of H-X are
eliminated from R-X; the product is very often an
alkene.
H
CH3
CH2
C Br
CH3
base
CH2
CH3 C
+ HBr
CH3
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ALKYL HALIDES – Substitution reactions
H
HC
H
H
C
H

Br + OH
H H
H C C OH + Br
H H
This is a nucleophilic substitution or nucleophilic
displacement reaction on which OH displaces Br.
The C-Br bond is polar, and the carbon (⊕) is
susceptible to attack by an anion or any other
nucleophile.
ӨOH
is the nucleophile (species which “loves nuclei”
or has an affinity for positive charges).
BrӨ is the leaving group
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ALKYL HALIDES – Substitution reactions
CH3-CH2—Br + ӨOH  CH3-CH2—OH + BrӨ
The general reaction is:
R-X + NuӨ  R-Nu + XӨ
These are ionic reactions.
There are two possible ionic mechanisms for nucleophilic
substitution, SN1 and SN2.
S – substitution; N – nucleophilic;
1 – unimolecular (the rate determining, r.d.s., step entails
one molecule);
2 – bimolecular (the rate determining step entails two
species).
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ALKYL HALIDES
The unimolecular (SN1) reaction
(a)
R
X
R +
X
In the first step, R-X dissociates, forming a carbocation,
R⊕, and the leaving group XӨ.
This is a slow, rate determining step (r.d.s.) and
entails only one species, R-X.
(b)
R⊕+ NuӨ  R-Nu
In the second step the carbocation and the nucleophile
combine. This occurs rapidly.
The overall reaction is R-X + NuӨ  R-Nu + XӨ
The rate of the reaction = k[R-X]
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Other Aspects of SN1 Reactions
X
1
(a) R
1
3
C R
R2
slow R
1
3
R
C
2
R
+ X
R
carbocation
(b)
Nu
3
R
C
2
R
fast
Nu
R1 C R3
R2
The most important feature of SN1 reactions is
the carbocation intermediate.
A. Alkyl halides which form stable
carbocations will undergo SN1 reactions.
3o alkyl halides form 3o carbocations (stable)
and will
 undergo SN1 reactions.
X
1
(a) R
1
3
C R
2
R
slow R
1
3
R
C
2
R
+ X
R
carbocation
(b)
Nu
3
R
C
R2
fast
Nu
R1 C R3
R2
Alkyl halides which form stable carbocations will
undergo SN1 reactions.
2o alkyl halides form 2o carbocations (fairly stable)
and it undergo SN1 reactions.
1o carbocations are unstable, 1o alkyl halides will not
undergo SN1 reactions.
Substitution reactions of 1o alkyl halides proceed
via the SN2 mechanism.
ALKYL HALIDES: The bimolecular (SN2)
reaction
(a) NuӨ + R-X ⇋ ӨNu---R---XӨ
The nucleophile and the alkyl halide combine to form a
pentacoordinate transition state. This is the slow rate
determining step (r.d.s); it entails two species, R-X and
NuӨ . The dotted lines indicate partially formed or
partially broken covalent bonds.
(b)
ӨNu---R---XӨ  Nu-R
+ XӨ
The pentacoordinate transition state dissociates to form
the product, Nu-R, and the halide ion (the leaving
group).
The rate of the reaction = k[R-X][NuӨ]
The rate is dependent of the concentration of two species;
higher concentrations increase the frequency of molecula
collisions.
ALKYL HALIDES: The bimolecular (SN2) reaction
(a) NuӨ + R-X ⇋
ӨNu---R---XӨ
The nucleophile and the alkyl halide combine to form a
pentacoordinate transition state. This is the slow rate
determining step (r.d.s); it entails two species, R-X and
NuӨ . The dotted lines indicate partially formed or
partially broken covalent bonds.
(b)
ӨNu---R---XӨ  Nu-R
+ XӨ
The pentacoordinate transition state dissociates to form
the product, Nu-R, and the halide ion (the leaving
group).
The rate of the reaction = k[R-X][NuӨ]
The rate is dependent of the concentration of two species;
higher concentrations increase the frequency of molecular
collisions.
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 • Reactivity of Alkyl Halide:
 Due to highly polar nature of Cδ+ − Cl δ bond ethyl






chloride is highly reactive.
Therefore alkyl halides are considered as synthetic tools
in the hands of organic chemistry.
Due to low bond dissociation energy, alkyl halides are
more reactive.
The order of reactivity of alkyl halides is as follows :
R - Cl < R – Br < R – I
CH3
CH3CH2CH2CH2−Cl <CH3CHCH2CH3 <CH3CCl
Primary
Cl Secondary
CH3tertiary
Chemical Reaction
Hydrolysis : With aqueous KOH ethyl chloride gives
R-X + aqueous alkali :OH-  ROH + :XCH3CH2CH2-Br +
alcohol
KOH  CH3CH2CH2-OH + KBr
R-X + alcoholic ammonia :NH3  R-NH2 + HX primary
amine
CH3CH2CH2-Br +
NH3  CH3CH2CH2-NH2 + HBr
 R-X +alcohlic pot. Cyanide :CN-  R-CN + :X- alkyl cyanide
(1) nitrile
 R-CN + H2O RCOOH + NH3
(2)
 CH3Cl+KCN CH3CN +KCl
 CH3CN + H2O CH3COOH +NH3

R’-X
+ RCOOAg RCOOR’ + AgX
esters
 CH3Cl + CH3COOAg  CH3COOCH3 + AgCl
• R-X + sodium alkoxide :OR´- 
R-O-R´ + :X- ether
• C2H5Cl + C2H5ONa  C2H5 O C2H5 + NaCl
• R-X + sodium sulfide :SR´  R-SR´ + :X- thio-ether
• CH3Cl + Na2S  CH3-S-CH3 + NaCl
• Formation of Grignard’s reagent
• R-X + Mg/ether RMgX
 C2H5 + Mg/ether C2H5MgI
Grignard’s reagent
 Reaction with Grignard’s reagent:
 R-X + R’MgX  R- R’ +MgX2
 CH3Cl + CH3MgCl  CH3-CH3 + MgCl2
 Wurtz reaction :
 In the presence of dry ether two moles of ethyl chloride reacts
with sodium to give butane.
 R-X + 2Na  R-R + 2 NaX
Alkane
 2 CH3Cl + 2 Na  CH3-CH3 + 2NaCl
 Reduction:
 R-X + H2/Pt  R-H + HX Alkane
 CH3Cl + H2/Pt  CH4 + HCl
 Elimination : In the presence of alcoholic KOH
 C2H5-Cl + alc KOH  C2H4 + HCl
Dihalogen derivatives
C n H 2n X 2
Di-Halogen Derivatives
Geminal Dihalides
|
|
Alkyl ene dihalide
CH2 CH2
CH
CH2
Alkyl idene dihalide
|
Dichloroethane
|
|
|
(Ethylidene dichloride)
1,1 -
|
|
Cl
CH3
|
|
Cl
|
C
Cl
|
H3C
C
|
Non - Terminal
Cl
|
Terminal
H
Cl
Cl
Cl
Cl
Ethylene dichloride
(1,2 -
Dichloroethane)
CH3
(Isopropylidene dichloride)
2,2 Dichloropropane
|
Vicinal Dihalides
CH3
propylenedichloride
(1,2
- Dichloro
propane)
Di-Halogen Derivatives
CH2 = CH2 + Cl — Cl(g) CCl4
Ethylene
CH2
|
Cl
|
ii) Preparation of Ethylene Dichloride
a ) Addition of Chlorine to Ethylene
CH2
|
Cl
Ethylene dichloride
1,2-Dichloroethane
Di-Halogen Derivatives
ii) Preparation of Ethylene Dichloride
b ) Action of Ethylene Glycol and PCl5
—
—
—
Cl
OH OH
Cl
Ethylene dichloride
+
Cl
—
H2 C — CH2 + 2 HCl + 2POCl3
H2 C — CH2
Cl
Cl — P
Cl
Cl
Cl
Cl
Cl — P
Cl
Cl
Ethylene glycol
1, 2-Ethanediol
1,2-Dichloroethane
Di-Halogen Derivatives
iii) Preparation of Ethylidene Dichloride
a ) Action of HCl and Acetylene
addtn
H — C = C — H + H+ — Cl—
—
—
Cl—
—
H—C  C—H +
H+
H
Cl
excess
Vinyl chloride
Ethenyl chloride
Acetylene
Ethyne
—
—
—
Cl
—
H
H
Cl
H—C—C—H
Ethylidene dichloride
1, 1-Dichloroethane
Di-Halogen Derivatives
iii) Preparation of Ethylidene Dichloride
b ) Action of Acetaldehyde with PCl5
Cl
Cl
CH3
H
|
C
|
|
|
||
O + Cl – P
Cl
Cl
Acetaldehyde Phosphorus
Pentachoride
Ethanal
CH3

|
H
|
C
+ POCl3
Ethylidene Phosphorus
Dichloride chloride
Di-Halogen Derivatives
iv) Distinction between Vicinal & Geminal Dihalides
by Hydrolysis reaction
|
+
CH2
|
Cl
K
K
|
|
OH OH (aq)
boil
Hydrolysis
Ethylene dichloride
1,2-Dichloroethane
H2 C
CH2
+ 2 KCl
|
|
OH OH
|
H2C
|
Cl
1,2-Ethane diol
(Glycol)
Hence aq alkali (NaOH /KOH) is used to distinguish between geminal and
vicinal dihalides
Di-Halogen Derivatives
|
|
H
|
H3C C Cl + K OH
|
K OH
Cl
Ethylidene dichloride
1,1-Dichloroethane
Boil
Hydrolysis
– 2KCl
|
|
|
H
H
|
|
– H2O
H3C C = O
H3C C OH
|
Acetaldehyde
OH
Ethanal
unstable
It gives aldehyde or ketone depending on the position of the halogen
atom
Tri-Halogen Derivatives
A ] Chloroform ( CHCl3 )
ii) Oxidation of Ethyl alcohol
Oxidation
H3C
C
|
H
||
Ethyl alcohol
Ethanol
H + Cl2
|
O
|
|
|
H3C
H
|
C
|
H
O + 2HCl
Acetaldehyde
(Ethanal)
Tri-Halogen Derivatives
A ] Chloroform ( CHCl3 )
|
iii) Chlorination of Acetaldehyde
Chlorination
CH3CHO
3Cl2
+
CCl3 CHO + 3HCl
Acetaldehyde
Trichloroacetaldehyde
Ethanol
(Choral)
iv) Hydrolysis of Choral
Ca
H
||
O
H
|
CCl3 – C
O
Hydrolysis
+
||
H
|
O H
CCl3 – C
O
(Chloral)
Calcium Hydroxide

2 CHCl3 + (HCOO)2Ca
Chloroform Calcium formate
(Trichloromethane)
Tri-Halogen Derivatives
1. Is Colorless , volatile , and Heavy liquid with sweet smell
2. Boiling point – 334 K
3. It is Insoluble in water but readily soluble in alcohol & ether
4. Is heavier than water
5. Produces unconsciousness when inhaled
6. Its vapour burns with a green edged flame
7. In liquid form , it is non-inflammable
Tri-Halogen Derivatives
i) Oxidation
Chloroform in presence of sunlight gives highly Poisonous gas
phosgene carbonyl chloride hence:
It is always stored In dark or amber colored bottles
2CHCl3 + O2
Chloroform
Trichloromethane
Sunlight
Air
2COCl2 + 2HCl
Phosgene
Carbonyl chloride
Tri-Halogen Derivatives
ii) Action with Concentrated nitric acid
Cl
Cl
|
|
|
|
|

Cl C H+ HO NO2 - H2O Cl C NO2
Con.
Cl
Cl
Nitro chloroform (chloropicrin)
Chloroform
CCl3 – NO2 is used as insecticide, tear gas.
Tri-Halogen Derivatives
iv) Hydrolysis
H
|
C
OH Unstable
OH
– H2O
OH
H2O + HCOOK
Potassium
Formate
KOH
H C = O
Formic acid
Methanoic acid
|
C
|
|
Boil
Cl + 3 K OH
(aq) Hydrolysis
Cl
-3 KCl
Chloroform
Trichloromethane
H
|
OH
Cl
Tri-Halogen Derivatives
v) Hofmann’s Carbylamine Reaction
NH2
+ CHCl3 + 3 KOH
(alc)
(C6H5NH2)
Aniline
Phenyl amine
NC
warm
+ 3KCl+ 3H2O
(C6H5NC)
Phenyl isocyanide
Phenyl Carbylamine
Alcohols
R-O-H
Classification CH3, 1o, 2o, 3o
Nomenclature:
Common names: “alkyl alcohol”
IUPAC: parent = longest continuous carbon
chain
containing the –
OH group.
alkane drop -e, add –ol
prefix locant for –OH (lower number for OH)
Alcohols classified as:
primary, 1o
secondary, 2o
tertiary, 3o
according to their "degree of substitution."
Degree of substitution is determined by
counting the number of carbon atoms
directly attached to the carbon that bears the
hydroxyl group.
Substitutive Nomenclature of Alcohols
Name as "alkanols." Replace -e ending of alkane
name by -ol.
Number chain in direction that gives lowest number
to the carbon that bears the —OH group.
CH3CH2OH
CH3
CH3CCH2CH2CH3
CH3CHCH2CH2CH2CH3
OH
OH
Substitutive Nomenclature of Alcohols
Name as "alkanols." Replace -e ending of alkane
name by -ol.
Number chain in direction that gives lowest number
to the carbon that bears the —OH group.
CH3CH2OH
Ethanol
CH3CHCH2CH2CH2CH3
OH
2-Hexanol
CH3
CH3C CH2CH2CH3
OH
2-Methyl-2-pentanol
Classification
H
CH3CH2CH2CH2CH2OH
OH
primary alcohol
secondary alcohol
CH3
CH3CHCH2CH2CH3
OH
secondary alcohol
CH3CCH2CH2CH3
OH
tertiary alcohol
Methods of Preparation
1-Reduction of Aldehydes/Ketones
Hydrogenation 
H2
R C H Pt
O
RCH 2OH Primary ROH
H2
R C R'
Pt
O
H
R C R'
OH
Secondary ROH
2- Hydrolysis of Alkali halide
R-X + aqueous alkali :OH-  ROH + :X- alcohol
3- Indirect hydration of Olefins
CH3CH=CH2 + H.HSO4 CH3-CH-CH3 HOH
HSO4
CH3CHCH3 + H2SO4
OH
Reduction of Aldehydes/Ketones
Hydride Reductions 
LiAlH 4
RCH
RCH 2OH
or
O
NaBH 4
R C R'
O
LiAlH 4
or
NaBH
4
H
R C R'
OH
Primary ROH
Secondary ROH
Reduction of Carboxylic Acids and
Esters
Lithium Aluminum 
Hydride Reduction
R
C OH
LiAlH 4
RCH 2OH + OH -
O
R
C OR'
O
LiAlH 4
RCH 2OH + R'OH
Grignard Addition
Reactions
 Addition to Aldehydes/Ketones
 Addition to Esters
 Addition to Epoxides
Grignard Additions to Esters
 Formation of secondary and tertiary
alcohols
H
C OR + 2R'MgX
R' 2CHOH + ROH
O
Secondary ROH
R'
R" C OR + 2R'MgX
O
R" C OH + ROH
R'
Teriary ROH
Properties of Alcohol
 1-Position isomerism:
 Compounds having the same molecular formula but differ
in the position of the functional group OH group
 C4H9OH → CH3CH2CH2CH2OH
 CH3CHCH2CH3
OH
1-butanol
2-butanol
2- Chain Isomerism
Depends on the type of the carbon chain;
Straight or Branched.
CH3CHCH2 OH
CH3
CH3CH2CH2CH2OH
iso-butanol
1-butanol
Optical Isomerism
 It present in alcohols which contain asymmetrical
carbon atom.
 Where the molecule has two isomers called
enantiomers, which they are optical active
 CH3CHCH2 OH
iso-butanol

CH3
 CH3CH2CH2CH2OH
1-butanol