Presentation apc
- 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
- 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
- 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
- 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
- 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;
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