Topic 6 – Alkyl halide and carbonyl compounds

Organic compounds containing a halogen

 
 Compounds are named in standard way, eg: 
 
  CH3
H 3C Cl CH 3
  1 C 2 CH 3
3
 
  I 4-chlorotoluene
2-iodo-2-methylpropane (aryl halide)
 
(tertiary alkyl halide)
  1 5
 
 
CHCl3 Br Br
 
trichloromethane 2,4-dibromopentane
  (chloroform) (two secondary alkyl halides)
 
1 5
 
CCl4
 
tetrachloromethane
  (carbon tetrachloride) Br Br
  (2R, 4R)-2,4-dibromopentane
  (two secondary alkyl halides)
 
 

Structure and properties

 Dense liquids and solids which are insoluble in water . 
 The C‐X bond is polar with a slight positive charge (+)   
residing on the carbon end of the bond and a slight  C X X = F, Cl, Br or I
negative charge ( ‐) on the halogen end . 
 The carbon‐halogen bond strength decreases in the  dipole moment
order C‐F > C‐Cl > C‐Br > C‐I.   
 Alkyl fluorides tend to be less reactive than other alkyl halides, mainly due to the higher 
strength of the C‐F bond. 
 

  Bond length (pm)  Bond strength (kJ mol‐1)  Dipole moment (D) 

CH3‐F  139  452  1.85 

CH3‐Cl  178  351  1.87 
CH3‐Br  193  293  1.81 
CH3‐I  214  234  1.62 

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 1. Nucleophilic substitution
 
  Electrophile: A species that seeks an electron pair
  Nucleophile: A species that supplies an electron pair
 
 
   
  Nu + H3C X Nu CH3 + X
 
nucleophilic
  nucleophile electrophile
substitution
 
  Nu + H3C X Nu CH3 + X
   
 
Examples: 
 
  A wide range of charged and uncharged nucleophiles may be employed
 
 
Nucleophile + H3C I Product + I Product class
 
 
  HO + H3C I H3C OH + I alcohol
 
 
  RO + H3C I H3C OR + I ether
 
 
 N C + H3C I H3C C N + I nitrile
 
 
R  C C + H3C I H3C C C R + I alkyne
 
 
  H2N + H3C I H3C NH2 + I amine
 
 
  R3N + H3C I H3C NR3 + I tetraalkylammonium
salt
 
 
 
Question: Draw the organic 
 products in the following   CN
reactions: 
  Br OH
 
 
 
  NH2

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Mechanism – SN2 (2nd order)
 
  H3CH2C CH2CH3 CH2CH3
  ~1/2 ~1/2
  CH3O C Br H3CO C Br CH3O C Br
 
  H H
  CH3 H CH CH3
3
  leaving
nucleophile electrophile transition state group
 
 
 
 
SN2 reaction favoured by a  H Me
primary alkyl halide as the  C X C X
starting material. 
Nu H Nu H
  H H
  methyl halide primary alkyl halide
  relative rate: 2,000,000 (FAST) 40,000
  Me Me
 
  C X C X
  Nu
Me Me
H Nu Me
 
  secondary alkyl halide tertiary alkyl halide
  relative rate: 500 <1 (V. SLOW)

 
 

Mechanism – SN1 (1st order)

 
carbocations have sp2
 
hybridised carbons (trigonlal
planar) with a vacant p-orbital
 
CH3 Attack of nucleophile to
either side of the planar  
CH3
C Br carbocation intermediate  
H3C C is equally likely!
CH3 H3C  
CH3
 
vacant p-orbital slow  
CH3
 
CH3
CH3
HO OH
 
HO C C C OH  
fast fast
H3C  
CH3 H3C CH H3 C
CH3 3  
planar + Br
 
carbocation leaving
intermediate group  
 

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Evidence for SN1 mechanism
Intermediacy of a planar carbocation intermediate means that any stereochemistry
in the starting material is lost on conversion to the product.

The nucleophilic substitution of (R)-3-bromo-3-methylhexane with methanol leads

to racemic methyl ether product
H3C Br CH3
slow + Br

(R)-3-bromo-3-methylhexane planar carbocation intermediate

CH3OH CH3OH
rate determining step fast 50% inversion
H3C OCH3 H3CO CH3
50% retention
+

(R)-3-methoxy-3-methylhexane (S)-3-methoxy-3-methylhexane
SN1 stands for substitution, nucleophilic, unimolecular.

Unimolecular refers to the fact that only one molecule, the alkyl halide, is involved in the
slow rate determining step. The reaction rate is therefore determined by the
concentration of the alkyl halide
Reaction Rate  [electrophile]
 

Carbocations
 
The intermediate in an SN1 reaction is a carbocation. 
 The C atom has six electrons and a positive charge. 
 This is an unstable, highly  H3 C H 3C H 3C H
reactive intermediate.  C CH3 C H C H C H
 Not all carbocations have the  H3C H 3C H H
a tertiary alkyl a secondary alkyl a primary alkyl a methyl
same relative (un)stability .  carbocation carbocation carbocation carbocation
  most least
stable increasing stability stable
 
 
 
 
H H3C
 
  C X C X
SN1 reaction more likely when a 
H H
tertiary carbocation is the  H H
intermediate  methyl halide primary alkyl halide
relative rate: (V. SLOW) <1 1
 
H3C H3C
 
  C X C X
 
H3C H3C
H H3C
secondary alkyl halide tertiary alkyl halide
relative rate: 12 (FAST) 1,200,000

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Comparison of SN1 and SN2
  Summary SN2 reaction: Summary SN1 reaction:
 
  Substitution, nucleophilic, second order Substitution, nucleophilic, first order
 
The reaction rate is determined by the The reaction rate is determined by the
  concentration the electrophile only
concentration of both nucleophile and
  electrophile
  Involves the two step substitution of an
  Involves the direct, single step alkyl halide by a nucleophile via a
  substitution of an alkyl halide by a carbocation intermediate
  nucleophile with no intermediates The SN1 reaction of chiral compounds
  The S 2 reaction proceeds with proceeds with racemisation
N
  inversion
  The rate of the SN1 reaction of alkyl
  The rate of the SN2 reaction of alkyl halides decreases in the order 3° >> 2° >
1° > methyl
  halides decreases in the order methyl >
1° > 2° >> 3°
  Usually only 3° alkyl halides react by this
  Usually only methyl, 1°and 2° alkyl pathway
  halides react by this pathway - less
  crowded
 
 
Question: Fill in the missing reagents. 
 

N(CH3)3 I

OH I
OCH2CH3
+ NaI
+ NaI

+ NaI
C
C
CH3

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 2. Elimination of HX
 
Dehydrohalogenation – require H and X on adjacent carbons. 
 Generally concentrated reagents and elevated temperatures are used. 
 Concentrated OH– is used (often KOH in ethanol solvent). 
 

H3C c. OH c. OH H3C
heat H3C heat
HC CH2 HC CH2
HC CH2
H Br Br H

+ H2O + Br
1-bromopropane 2-bromopropane  
 
Zaitsev’s Rule applies – where there is a choice, the most substituted alkene forms. 
 

c. OH H3C HC CH CH3 + H2O + Br

H heat
H3C CH C CH2 major product
H Cl H

H3C H2C HC CH2 + H2O + Br

R R
C C R R
H H R H R R
H H C C
C C C C C C
H H H H R H R H R R
C C
R H
unsubstituted monosubstituted disubstituted trisubstituted tetrasubstituted
ethylene alkene alkene alkene alkene
 
 

 
Br
hot, conc K OH
Examples of eliminations   + H 2O + K Br
ethanol
 
  H3C H3C
hot, conc H2SO4
  H3C C OH C CH2 + H2O
  H3C H3C
 
  hot, conc K OH + H2 O
  ethanol +K Cl
  Cl
major minor
trisubstituted C=C bond disubstituted C=C bond
3 carbon substituents 2 carbon substituents

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Question: Fill in the reagents in the following sequence of reactions. 
 
OH
OH

Br

Br  
 
 
 
 

3. Formation of Grignard reagent

 
This is the reaction of an alkyl‐ or aryl‐halide and magnesium. 
 
    
  X = Cl, Br, I
R X + Mg R Mg X
  R = alkyl, aromatic
 
 
  eg CH3Br + Mg CH3MgBr
 
 
+ Mg
 
  I Mg I
 
Cl MgCl
 
  + Mg
 
 
 

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Carbonyl Compounds – aldehydes and ketones
 The double bond is composed of one σ and one π bond.  H
 The electron density of a π bond is above and below the plane of the   
double bond.  C O
 The C=O double bond is polarised. 
 Aldehydes have at least one H attached to the carbonyl group, ketones 
have two carbon groups attached to the carbonyl group.  H
 2
Carbon of the carbonyl group is sp  hybridised.  
  overlap of electrons in p-orbitals
  give rise to a -bond
 
 
 
H oxygen has two lone
  H C O pairs of electrons
  C O H
  H
 
 
  overlap of electrons in sp2-hybridised
  orbitals gives a -bond
in formaldehyde, overlap of electrons
  in an sp2-hybridised orbital from C and
a 1s orbital from H gives a -bond

Nomenclature
Aldehydes 
 The longest chain containing the CHO group gives the stem; ending –al. 
 If substituents are present, start the numbering from the aldehyde group ‐ C1. 
 
Ketones 
 The longest chain containing the carbonyl group gives the stem; ending –one. 
 If substituents are present number from the end of the chain so the carbonyl group has the 
lowest possible number. 
 
 There are non‐systematic names for the common aldehydes and ketone, for example: 
  CH3CH2CH2
H CH3 CH3CH2
 
C O C O C O C O
 
  H H H H
 
  formaldehyde acetaldehyde propionaldehyde butyraldehyde
  (methanal) (ethanal) (propanal) (butanal)
 
  O O
 
  CH 3 C C
C O H CH3
 
  CH3
 
acetone
benzaldehyde acetophenone
(propanone)
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Question:  Name the following compounds.  O
 
  O O
  CH2O
  O O
 
 

Reactions of carbonyl group – nucleophilic addition

 
Dominated by weak and accessible π‐bond 
 Polarity of C=O directs addition reaction  
 Reaction conducted in two stages 
 Nucleophile (eg hydride or carbanion) adds to C  
 Then O– adds to H+ 
  H
  H H
  H
C O H
  Nu C O
Nu
C O
stage 1 stage 2 Nu
  H
H H
 

1. Hydride addition (reduction)

 
Use H– (LiAlH4 or NaBH4) followed by H+ 
 Aldehydes give primary alcohols, ketones give 
secondary alcohols 

Examples: 
 
  R  R R
H H
 
H C O H C O H C O
 
H H H
 
  primary
  alcohol
 
 
  R  R R
H H
 
H C O   H C O H C O
R R R

secondary
alcohol

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 2. Grignard reaction
C nucleophile
 
This is a very versatile reaction.  use Grignard reagent: RMgX
 Can use most organohalide compounds to generate Grignard  R Mg X
reagent. 
 Grignard reagent reacts with aldehydes, ketones and CO2. 
 Must employ anhydrous conditions. 
  R Mg X

 
Examples: 
 
  H  H H
H H
  HC C O
3 H3 C C O H3 C C O
  STEP 1 STEP 2
H H H
  MgBr nucleophilic MgBr acid-base
 
methyl addition reaction a primary
formaldehyde an alkoxide
 
magnesium anion alcohol
bromide
 
 
 
 
  R  R R H
H
  H3 C C O H3 C C O H3 C C O
  H H H
  MgBr MgBr
 
methyl other aldehydes secondary
magnesium
  alcohol
bromide
 
 
 
  R  R R
H H
 HC C O
3 H3 C C O H3 C C O
 
R R R
  MgBr MgBr
 
methyl tertiary
all ketones
 
magnesium alcohol
bromide
 
 
 
  O  O O
H
  H3 C C  H3 C C H3 C C
  O  O O H
  MgBr
 
methyl carbon dioxide
MgBr carboxylic
 
magnesium acid
bromide
 
 

49
Question: Draw the products of the following sequence of reactions.  
 

Cl conc KOH
heat dil H2SO4

2 products, use
one in next step

Cr2O72 /H

conc H2SO4 1. CH3CH2MgBr

heat 2. H

 
 
 
Question: In the Grignard reaction to form 3‐methylhexan‐3‐ol there are three possible ketones 
that could be used as a starting material.  Identify the three ketones and the Grignard reagent 
they need to react with to give the desired product.  

50