2. SUBMITTED TO:
Ms. S.D. Vachala
Dept of Pharmaceutical Chemisty
M.C.O.P.S. Manipal
SUBMITTED BY:
DEPARTMENT OFPHARMACEUTICAL
Shikha Tyagi
CHEMISTRY M. PHARM- I
MCOPS MANIPAL 100602017
Dept of Pharm. Chem.
M.C.O.P.S. Manipal

3. Contents
1 Addition to carbon carbon multiple bond
•Electrophilic addition
•Nucleophilic addition
•Free radical reaction
•Orientation
•Reactivity
•Reactions
2 Addition to carbon hetero bond
•Addition
Addition to
•Addition to
•Addition to

4. Addition to Carbon–Carbon
Multiple Bonds
 Electrophilic
 Nucleophilic
 Free radical

5. Electrophilic addition
Mechanism
Step1
Step2

6. Electrophile can be:-
•A positive ion.
•The positive end of a dipole or an induced dipole, with the negative part breaking off either during
the first step or shortly after..
Addition to a double bond
There are thus three possibilities.
•Both Y and W may enter from the same side of the plane, in which case the addition is stereo
specific and Syn.
•They may enter from opposite sides for stereospecific anti addition.
•The reaction may be nonstereospecific.

7. stereospecificity
On double bond
reactant addition product
cis Syn Erythro
cis Anti Threo
trans Syn Threo
trans Anti Erythro
On triple bond
Syn gives cis olefin
Anti gives trans olefins

8. Reactions
syn
Anti

9. Nucleophilic Addition
Step 1
step2

10. Free-Radical Addition
Initiation
Propagation
Termination

11. Reactivity
Electrophilic addition:-
•Electron-donating groups increase the reactivity of a double bond toward electrophilic addition
•electron-withdrawing groups decrease reactivity .
•The reactivity toward electrophilic addition of a group of alkenes increased in the order :-
Nucleophilic addition:-
The situation is reversed.

12. SOME IMPORTANT FACTS
Comparison between double and triple bonds. There is a higher concentration of
electrons between the carbons of a triple bond than in a double bond, and yet triple
bonds are less subject to attack at an electrophilic site and more subject to nucleophilic
attack than double bonds.
This statement is not universally true, but it does hold in most cases. In compounds
containing both double and triple bonds (nonconjugated), bromine, an electrophilic
reagent, always adds to the double bond. In fact, all reagents that form bridged
intermediates react faster with double than with triple bonds.
EXPLANATION TO THE FACT:
As mentioned, it is true that in general triple bonds are more susceptible to nucleophilic
and less to attack on an electrophilic site than double bonds, in spite of their higher
electron density.Because:-
•The electrons in the triple bond are held more tightly because of the smaller carbon–
carbon distance; it is thus harder for an attacking electrophile to pull out a pair.
•The availability of the unfilled orbital in the alkyne.

13. Orientation
For electrophilic attack, the answer is given by
Markovnikov’s rule: The positive portion of the reagent goes to the side of the doubleor triple bond that
has more hydrogens.
Why does Y+ add to give the more stable carbocation? As in the similar case of electrophilic
aromatic substitution we invoke the Hammond postulate “ say that the lower energy carbocation is
preceded by the lower energy transition state.”

14. Stereochemical Orientation
In addition to an unsymmetrical cyclic alkene, the two groups can come in from the more- or from the
less-hindered face of the double bond.
The rule is that syn addition is usually, although not always, from the less-hindered face.
For example, epoxidation of 4-methylcyclopentene gave 76% addition from the less-hindered and 24%
from the more-hindered face

15. Reactions
Addition of HCL
Mechanism

16. The slow or rate determining step is the protonation of
the alkene to form a carbocation. The reaction will take
the lowest energy course at this stage. The most stable
carbocation will form by rearrangment. This determines
the regioselectivity of the reaction.

17. Rearrangement via hydride shift or methyl
Hydride
shift
Methyl shift

18. Rearrangement to form stable carbocations

19. Addition according to markovnikov’s rule

20. Addition of HBr by free radical mechanism—
Antimarkovnikove’s rule
•When peroxides are added, the addition of HBr occurs by a free radical mechanism
and the orientation is anti-Markovnikov
•Free-radical addition of HF and HI has never been observed., even in the presence of
peroxides
•Free-radical addition of HF, HI, and HCl is energetically unfavorable
•It has often been found that anti-Markovnikov addition of HBr takes place even when
peroxides have not been added. This happens because the substrate alkenes absorb
oxygen from the air, forming small amounts of peroxides

21. Adding water (H � OH) across the double bond
The simplest way is to reflux water and alkene with acid
catalyst essentially the same as H-Cl etc. It is a difficult
reaction requiring quite forcing conditions.
Mechanism

22. In presence of strong acid polymation product is obtained
mechanism

23. Hydroboration
mechanism
anti-Marknikov

24. Addition of Br2- product form analogus to HBr addition
Mechanism- addition is anti

25. Not formed product

26. Addition to Alkynes
This is much more complex. The reason is that the cation is sp hybridized and is
much less stable
hydrogenation

27. Addition to carbon
heteromultiple bonds

28. the addition reaction to the carbon hetro multiple bonds
•Carbon nitrogen bond
1.
2 C=N
•Carbon oxygen bond.
•-C=O
Since C=O, C=N, and C≡N bonds are strongly polar, with the carbon always the
positive end (except for isocyanides, ),

29. Addition to
mechanism
•Who attack first ???????????
•Always nucleophile attack first ,in some cases electrophile may attack
but rate determining step is always addition of nucleophile.
•How they will attack???????????????
•If at beta position electron withdrawing group is present ------- syn
•If at beta position electron releasing grouup is present -----------anti

30. Reactivity
•Base ---- by donating its electrons to the nucleophile make it more powerful
nucleophile to attack on carbon
•Acid ---- increase positive charge on carbon increase its reactivity towards
the nucleophile
•A &B electron donating ---------decrease activity
•A & B electron withdrawing------- increase activity.
•Conjugation ------------------------------increase activity
•Steric hinderence ------------------------------decrease activity
•Aromatic aldehyde and ketones are more reactive than the aliphatic
aldehyde and ketones.

31. Reactions
Attack by hydroxyl group
The Addition of Water to Aldehydes and Ketones: Formation of Hydrates
Gemdiol(hydrateadduct)
Mechanism
(Acid)
Stable only in water
(Base)

32. Stability of hydrate
+I ------------- decrease the stability
--I -------------- increase the stability
Eg
1 Hydrate of chloral are stable

33. Addition of water to carbon nitrogen double bond
mechanism
Reagents used to cleave carbon nitrogen double bond
1 Th(III) nitrate
2 Aq TiCl3
3 CH3COOH
W------OH (oximes)
W-------NHCONH2
(semicarbazone)
W--------- NHAr(arylhydrazone)
W--------Ar(shiffs base)

34. Hydrolysis of Aliphatic Nitro Compounds
reaction
mechanism
Hydroxamic acid
intermediate

35. To increase the yield
1Aq TiCl3
2 NaHSO3
3 activated dry silicagel
If concentration of sulphuric acid is increased fro 2M to 15.5M may change
aldehyde back to hydroxamic acid

36. . Attack by OR or SR (Addition of ROH; RSH)
mechanism

37. For acid------------ NaOH with 6-12% H2O2 is used
TO stop at amide--------- Conc H2So4, HCOOH with HCl or HBr,sodium
percarbonate is used

38. reaction
mechanism

39. reaction
Mechanism - it is not clear
Eg
Isocyanic acid carbamate

40. The addition of dry HCl to a mixture of a nitrile and an alcohol in the
absence of water leads to the hydrochloride salt of an imino ester
(imino esters are also called imidates and imino ethers). This reaction is
called the Pinner synthesis

41. Attack by ammonia derivatives on
carbonyl compounds
Mannich reaction:The Mannich reactio consists of an amino alkylation of an
acidic proton placed next to a carbonyl functional group with formaldehyde
and ammonia or any primary or secondary amine. The final product is a β-
amino-carbonyl compound also known as a Mannich base

42. mechanism
Step1 ---formaldehyde + amine = amine
Step2 ---ketone---- enole form
Step3--- enol form--- cabanion
Step 3--- imine form carbocation
Step 4---- carbocation + carboanion= mannich base

43. Addiition of hydrazine derivative
Formation of :-
1 hydrazone
2 osazone
3 pyrazolone
hydrazone
The product of condensation of a hydrazine and an aldehyde or ketone is
called a
hydrazone.

44. osazone
α-Hydroxy aldehydes and ketones and a-dicarbonyl compounds give osazones, in
which two adjacent carbons have carbon–nitrogen double bonds

45. Pyrazolone
beta keto esters gives pyrazolones

46. Attack by hydroxyl amine
oximes can be prepared by the addition of hydroxylamine to aldehydes or
ketones.
mechanism

47. Important
•Maximum rate at pH 4
•Step 1 is base catalysed at high pH hydroxylamine will be protonated and
can not attack to the carbonnyl carbon
•Step 2 is acid catalysed
•Step I is slow and rate determining
•At high pH rate determining step will be step2

48. Attack by halogen
Formation of gem halide
In presence of alpha carbon vinylic chloride will be as side product or
soetimes main product

49. Attack by organo mettalic compounds
Grignard reaction
Organomagnesium compounds, commonly known as Grignard reagents
(RMgX), are formed by the reaction of alkyl, vinyl, or aryl halides with
magnesium
metal, usually in ether solvents such as diethyl ether or THF
•Formaldehyde -------------primary alcohol
•Other aldehyde --------- sec alcohol
•Ketone --------- tertiary alcohol

50. Reformatsky reaction
Alpha halo ester
Beta hydroxy acid
Inermediate
Reactivity increased
by:-
1 activated zinc
2 zinc/silver graphite
3 zinc and ultra sound

51. Carbon Attack by Active Hydrogen Compounds
Aldol rections
Reactions are base-catalyzed condensations. base removes a CH proton to give a
carbanion, which then adds to a CO. The oxygen acquires a proton, and the resulting
alcohol may or may not be dehydrated, depending on whether an a hydrogen is
present and on whether the new double bond would be in conjugation with double
bonds already present.
Retrograde aldol reaction becauuse all the steps are reversible

52. Scope of aldol reactions
1. Two same aldehyde with alpha H
2. Two same krtone wiith alpha H
3. Two different alldehyde one may not haver alpha H
4. Two different ketone
5. One aldehyde and one ketone.:-feasable if aldehyde has no alpha hydrogen
,if aldehyde also having alpha hydrogen only alpha carbon of the ketone will
add to the carbonyl cabon of aldehyde

53. The Knoevenagel Reaction
The condensation of aldehydes or ketones, usually not containing an a
hydrogen, with compounds
Reaction

54. The Perkin Reaction
The condensation of aromatic aldehydes with anhydrides is called the Perkin
reaction
Base is generally the salt of acid corresponding to the acid anhydride,.
Alpha hydroxy never isolated always dehydrated to form α-β unsaturated
compounds
When acid anhydride contains only one active methylene hydrogen then
hydroxy compounds can be isolated.

55. Tollens’ Reaction
In the Tollens’ reaction an aldehyde or ketone containing an α hydrogen is
treated with formaldehyde in the presence of Ca(OH)2 or a similar base.
mechanism

56. If aldehyde and ketone having several α hydrogen they all can be
replaced
Pentaerythritol

57. Benzoin condensation
When certain aldehydes are treated with cyanide ion, benzoins are produced
in a reaction called the benzoin condensation
reaction
Mechanism

58. Addition to carbon sulpher
bond
Nucleophilic substitution at RSO2X is similar to attack at RCOX
Reaction

59. Description
•Sulfonyl chlorides as well as esters and amides of sulfonic acids can be hydrolyzed to the corresponding
acids.
• Sulfonyl chlorides can by hydrolyzed with water or with an alcohol in the absence of acid or base
• Basic catalysis is also used but the salt is the product obtained..
• Usually involves R-O cleavage, except when R’is aryl.

60. REFERENCES
•Smith B. Micheal & March Jerry; ”March’s Advanced Organic
Chemistry, Reaction, Mechanism and Structures; Wiley-Interscience John wiley&
son inc, Publication, New Jersey; VI edition; 2007; 999-1476;

61. THANKYOU