Addition Reactions By O. Sailaja (Asst. Professor) PG Department of Chemistry KBN College

1. Addition Reactions By O. Sailaja(Asst. Professor) PG Department of Chemistry KBN College

2. Addition Reaction: • The reactions in which two molecules combine to give a single molecule of product are known as addition reaction. • The substrate of an electrophilic addition reaction must have a double bond or triple bond. Addition reactions are of two types Polar addition reactions: These are initiated by ions. These are classified into two types. a. Electrophilic addition reactions b. Nucleophilic addition reactions

3. Electrophilic Addition reactions: These are initiated by Electrophiles. Eg: Addition of bromine to C-C double bond to produce 1,2- dibromocompound. Nucleophilic Addition Reactions: These are initiated by Nucleophiles. Eg: Hydrogen cyanide adds across the carbon-oxygen double bond in aldehydes and ketones to produce compounds known as hydroxynitriles.

4. Non Polar Addition Reactions: These are initiated by free radicals but not by the ions. Eg: Addition of HBr to c-c double bond in the presence of peroxide.

5. The characteristic reaction of alkenes is addition—the  bond is broken and two new  bonds are formed. • Alkenes are electron rich, with the electron density of the  bond concentrated above and below the plane of the molecule. • Because alkenes are electron rich, simple alkenes do not react with nucleophiles or bases, reagents that are themselves electron rich. Alkenes react with electrophiles. • Because the carbon atoms of a double bond are both trigonal planar, the elements of X and Y can be added to them from the same side or from opposite sides.

7. Figure 10.8 Five addition reactions of cyclohexene

8. Hydrohalogenation—Electrophilic Addition of HX Alkenes react with hydrogen halides to form alkyl halides. This reaction is known as hydrohalogenation.

9. MECHANISM • The mechanism of electrophilic addition of HX to c-c double bond consists of two successive steps. • In step1 attack of electrophile (such as HBr) on  bond of alkene Produces carbocation and bromide ion. • Carbocationis an electrophile, reacting with nucleophilic bromide ion yielding the neutral addition product.

10. Regioselectivity—Markovnikov’sRule • Addition of non-symmetrical reagent to a non-symmetrical alkene then two isomeric products that are constitutional isomers can be obtained. • For example, the reaction of HCl with propene gives 1-chloropropane and 2-chloropropane. • Normally, 2-chloropropane is the major product. • Since one product is favoured over the other, the reaction is said to be regioselective. • If 2-chloropropane were the only product then the reaction is said to be regiospecific.

11. This is a specific example of a general trend called Markovnikov’s rule. • Markovnikov’s rule states that in the addition of HX to an unsymmetrical alkene, the H atom adds to the less substituted carbon atom—that is, the carbon that has the greater number of H atoms to begin with. • The basis of Markovnikov’s rule is the formation of a carbocation in the rate-determining step of the mechanism. • In the addition of HX to an unsymmetrical alkene, the H atom is added to the less substituted carbon to form the more stable, more substituted carbocation.

13. Hydrohalogenation—Reaction Stereochemistry • Recall that trigonal planar atoms react with reagents from two directions with equal probability. • Achiral starting materials yield achiral products. • Sometimes new stereogenic centers are formed from hydrohalogenation: A racemic mixture 

14. Hydrohalogenation—Reaction Stereochemistry • The mechanism of hydrohalogenation illustrates why two enantiomers are formed. Initial addition of H+occurs from either side of the planar double bond. • Both modes of addition generate the same achiral carbocation. Either representation of this carbocation can be used to draw the second step of the mechanism.

15. Hydrohalogenation—Reaction Stereochemistry • Nucleophilic attack of Cl¯ on the trigonal planar carbocation also occurs from two different directions, forming two products, A and B, having a new stereogenic center. • A and B are enantiomers. Since attack from either direction occurs with equal probability, a racemic mixture of A and B is formed.

16. Hydrohalogenation—Summary

17. Example of Markovnikov’s Rule

18. Markovnikov’s Rule • More highly substituted carbocation forms as intermediate rather than less highly substituted one • Tertiary cations and associated transition states are more stable than primary cations

19. Anti-Markovnikov’s Rule • MarkovnikovRule predicts the regiochemistry of HX addition to unsymmetrically substituted alkenes. • But some reactions do not follow Markovnikov's Rule, and anti-Markovnikov products are isolated. This is a feature for example of radical induced additions of HX and of Hydroboration. This was obsreved by Kharasch and Mayo. • Anti-MarkovnikovAddition Definition: • Anti-Markovnikovaddition is an addition reaction between an electrophilecompound HX and either an alkene or alkyne where the hydrogenatom of HX bonds to the carbon atom with the least number of hydrogen atoms in the initial alkene double bond  or alkyne triple bond  and the X bonds to the other carbon atom.

20. Chain initiation Chain propagation:An electrophilic bromine radical adds to the alkene to generate the 2o radical. This is more stable than the primary radical which would be formed when it is attached to other carbon. That radical reacts with another HBr molecule to produce 1-bromopropane and another bromine radical to continue the process. Chain termination Eventually two free radicals hit each other and produce a molecule of some sort. The process stops here because no new free radicals are formed.

21. Halogenation—Addition of Halogen • Halogenation is the addition of X2 (X = Cl or Br) to an alkene to form a vicinal dihalide.

22. Halogenation—Addition of Halogen • Halogens add to  bonds because halogens are polarizable. • The electron rich double bond induces a dipole in an approaching halogen molecule, making one halogen atom electron deficient and the other electron rich (X+—X–). • The electrophilic halogen atom is then attracted to the nucleophilic double bond, making addition possible. • Two facts demonstrate that halogenation follows a different mechanism from that of hydrohalogenation or hydration. • No rearrangements occur • Only anti addition of X2 is observed • These facts suggest that carbocations are not intermediates.

24. Stereochemistry: The reaction proceeds via a trans addition, but because of the free rotation possible around the single bond of the resulting alkane, a trans product cannot be isolated. however, the original alkene structure possesses restricted rotation due to a factor other than a double bond, a trans‐addition product can be isolated. If cyclohexene, a six‐carbon ring that has one double bond, is halogenated, the resulting cycloalkane is trans substituted.

25. Epoxidation: Reaction of alkenes with peracide gives epoxides and this reaction is known as epoxidation. • During the epoxidation of alkenes, an oxygen atom is transferred from the peracid to the C=C double bond thus forming an oxirane ring. • Since the transferred oxygen atom carries a positive charge, peracids must be considered electrophilic oxidizing agents. • Peracidsused are m-chloroperbenzoic acid (MCPBA), peroxybenzoicacid and peroxyacetic acid. • In addition to peracids, tert-butyl hydroperoxide (TBHP), dioxirane and alkaline hydrogen peroxide are frequently used .

26. C O O H C O O H 2 + C H C O O H M g 3 - C O Peroxyacetic acid C l (Peracetic acid) meta- chloroperoxy- Magnesium benzoic acid monoperoxyphthalate (MCPBA) (MMPP) O O O O 2

27. Mechanism: Epoxidation occurs via syn addition of an O atom to either side of a planar double bond. Thus, a cis alkene gives an epoxide with cis substituents. A trans alkene gives an epoxide with trans substituents. • Epoxidation is stereospecific because cis and trans alkenes yield different stereoisomers as products.

28. Reactions of Epoxides • Ethers are not normally susceptible to attack by nucleophiles • Because of the strain associated with the three-membered ring, epoxides readily undergo a variety of ring-opening reactions • Acid-catalyzed ring opening: • In the presence of an acid catalyst, such as sulfuric acid, epoxides are hydrolyzed to glycols.

29. Base-Catalyzed Epoxide Opening • Strain of the three-membered ring is relieved on ring-opening • Hydroxide cleaves epoxides at elevated temperatures to give trans 1,2-diols

30. Mechanism: Step 1: proton transfer to oxygen gives a bridged oxonium ion intermediate Step 2: backside attack by water (a nucleophile) on the oxonium ion (an electrophile) opens the ring Step 3:proton transfer to solvent completes the reaction • Hydrolysis of an epoxycycloalkane gives a trans-1,2-diol

31. the value of epoxides is the variety of nucleophiles that will open the ring and the combinations of functional groups that can be prepared from them

32. Treatment of an epoxide with lithium aluminum hydride, LiAlH4, reduces the epoxide to an alcohol • the nucleophile attacking the epoxide ring is hydride ion, H:- Adds –CH2CH2OH to the Grignard reagent’s hydrocarbon chain

33. Perhydroxylation • Oxidation of alkenes to 1,2 – diols is known as hydroxylation. • Depending upon the reagents used , hydroxylation takes place in two ways. • Cisperhydroxylation 2. Trans perhydroxylation • Cisperhydroxylation: Addition of two hydroxyl groups takes place to the same side of the c-c double bond.

34. The reagents used are • Alk KMnO4 (Bayers reagent) • OsO4 • I2/CH3COOH (moist)-Woodward reagent • Trans Perhydroxylation: Addition of two hydroxyl groups takes place to the opposite side of the c-c double bond. • The reagents used are • I2/CH3COOAg (dry) (Prevost condition) • Per acids

35. Alk KMnO4 (Bayers reagent): • Reactions of alkenes with cold dil alkaline KMnO4 gives cis 1,2-diols. • Good yields are obtained by effecting the oxidation in the presence of phase transfer catalyst such as quarternaryamm. Salts or crown ethers. Mechanism: Through the formation of cyclic manganese ester via syn addition. Cyclic manganese ester

36. Osmium tetroxide(OsO4 ): This is the best methods but it is suitable for only small scale. Because of its expensiveness and toxicity it is used in catalytic amounts. Mechanism: Takes place through the formation of cyclic osmate complex which on oxidative or reductive cleavage gives the corresponding diols.

37. The Woodward cis-hydroxylation is the chemical reaction of alkenes with iodine and silver acetate in wet acetic acid to form cis-diols. Cisdiol Trans diol

38. Mechanism:

39. oxidation of alkenes with per acids usually does not stop at the oxacyclopropane stage, but leads to ring-opening and the subsequent formation of a trans diol: Trans diol Hydrogenation: Addition of hydrogen to a multiple bond. Eg. Addition of hydrogen to ethylene gives ethane.

40. Reducing Agents • There are three types of reductions differing in how H2 is added. • The simplest reducing agent is H2. Reductions using H2 are carried out with a metal catalyst. • A second way is to add two protons and two electrons to a substrate—that is, H2 = 2H+ + 2e-. • Reductions of this sort use alkali metals as a source of electrons, and liquid ammonia as a source of protons. • These are called dissolving metal reductions.

41. The third way to add H2 is to add hydride (H¯) and a proton (H+). • The most common hydride reducing agents contain a hydrogen atom bonded to boron or aluminum. Simple examples include sodium borohydride (NaBH4) and lithium aluminum hydride (LiAlH4). • NaBH4 and LiAlH4 deliver H¯ to the substrate, and then a proton is added from H2O or an alcohol.

42. Reduction of Alkenes—Catalytic Hydrogenation • The addition of H2 occurs only in the presence of a metal catalyst, and thus it is called catalytic hydrogenation. • The catalyst consists of a metal—usually Pd, Pt, or Ni, adsorbed onto a finely divided inert solid, such as charcoal. • H2 adds in a syn fashion.

43. Mechanism of Catalytic Hydrogenation • Heterogeneous – reaction between phases • Addition of H-H is syn

44. Reduction of Alkynes • There are three different ways in which H2 can add to the triple bond:

45. Reduction of an Alkyne to an Alkane Alkane formation:

46. Reduction of an Alkyne to a Cis Alkene • Palladium metal is too reactive to allow hydrogenation of an alkyne to stop after one equivalent of H2 adds. • To stop at a cis alkene, a less active Pd catalyst is used—Pd adsorbed onto CaCO3 with added lead(II) acetate and quinoline. This is called Lindlar’s catalyst. • Compared to Pd metal, the Lindlar catalyst is deactivated or “poisoned”. • With the Lindlar catalyst, one equivalent of H2 adds to an alkyne to form the cis product. The cis alkene product is unreactive to further reduction.

47. Reduction of an alkyne to a cisalkene is a stereoselective reaction, because only one stereoisomer is formed.

48. Dissolving metal reduction of a triple bond with Na in NH3 is a stereoselective reaction because it forms a trans product exclusively. • Dissolving metal reductions always form the more stable trans product preferentially. • The trans alkene is formed because the vinyl carbanion intermediate that is formed is more stable when the larger R groups are further away from each other to avoid steric interactions. Protonation of this anion leads to the more stable trans adduct.

49. Reduction of Polar C—X  Bonds • Alkyl halides can be reduced to alkanes with LiAlH4. • Epoxide rings can be opened with LiAlH4 to form alcohols. Figure 12.6 Examples of reduction of C – X σ bonds with LiAIH4

50. NucleophilicAddition Reactions Nucleophilic addition reactions are an important class of reactions that allow the inter conversion of C=O into a range of important functional groups. Strong nucleophiles (anionic) add directly to the C=O to form the intermediate alkoxide.  The alkoxideis then protonated on work-up with dilute acid.