SUMMARY OF ORGANIC REACTIONS Karl Separa Imed 2018 Remember: When Carbocation in present in the intermediate, perform Hydride

Shift or Methyl Shift with the Halogen ion to achieve higher stability. Also take into account steric effects when choosing attachment site. RXN Reactant Catalyst, Solvent, Redox Agent Products Notes FREE RADICAL SUBSTITUTION Alkane (R) + X2 UV light, High Temperature R-X, H-X Use relative stabilities of radicals (3 > 2> 1) For Cl: use statistics (35.0, 23.8, 11.0) For Br: use stability of radicals Benzyl or Allyl + X2 Allyl + NBS (Nbromosuccinimide) Alkene (R) + H-X High temperature UV or High Temp in peroxide None R-X, H-X R-X, succinimide R-X Stability of radicals: benzyl, allyl, 3, 2, 1, vinyl, methyl Remember that internal alkenes are more stable than terminal alkenes Use carbocation/radical stability Use Markovnikov: Hydrogen bonds to Carbon with more H, Halogen bonds to Carbon with less H Hydration: Obey Markovnikov Obey Markovnikov Vicinal: Halogens are located in adjacent Carbons; Anti: Halogens at trans config; no carbocations formed hence no rearrangements Halohydrin (instead of 2 Halogens attached, 1 Halogen is replaced with OH group which was taken from the water solvent)

ELECTROPHILIC ADDITION

Halogenation with Alkene

R + H2O R + Alcohol R + X2 R + X2

Acid (H+) at 140C Acid (H+) Inert solvent (ex. CH2Cl2) In H2O

Alcohol, H3O Ether Always Vicinal-Anti dihalide Halohydrin, H-X

Hydrohalogenation

Alkyne (R) + H-X R + H2O R + X2

None Diprotic acid (ex. H2SO4) Inert solvent (ex. CH2Cl2)

Geminal dihalide Ketone-enol tautomerism Tetra-Haloalkane

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Special Reactions Oxymercuration - Reduction

R + H2O

Hg(OAC)2 and reduced by Sodium borohydride NaBH4 Diprotic acid (ex. H2SO4) in HgSO4

Alcohol, Hg, AcO , AcOH

2+

Reduction: increase in C-H bonds, decrease in C-O, C-N, C-X bonds; No carbocations formed hence no rearrangements

R + H2O

Ketone-enol, H2O, Hg

Hydroboration Oxidation

Borane BH3 accepts e- pair, adding NaOH, Hydrogen Peroxide H2O2 and H2O

Alcohol

Anti-Markovnikov: in BH3, one Hydrogen attaches to C of alkene with less number of Hydrogen atoms and remaining BH2 attaches to the other Carbon; BH2 is then replaced by OH group; No rearrangements due to carbocation Anti-Markovnikov

Disiamylborane accepts e- pair, adding adding NaOH, Hydrogen Peroxide H2O2 and H2O Peroxide Metal Catalyst (Pt, Pd, Ni)

Aldehyde (if terminal alkene is used)

Addition of Peroxide Hydrogenation

R + H-X R + H2

R-X R

Anti-Markovnikov, No rearrangements Metal catalysts are insoluble in the mixture; When hydrogenated, alkene releases heat (heat of hydrogenation); The two Hydrogen attach themselves to the 2 Carbons involved in the double bond; Smaller heats=more stable; alkyl substituents bonded to C-atoms of alkene has stabilizing effect = More alkyl subsitutents, greater stability or fewer Hydrogens, greater stability.

R + H2

Metal Catalyst

R R

Reaction can be stopped at Alkene stage using Lindlar Catalyst (precipitating Pd on CaCO3 and treating it with Pb (II) acetate and quinoline); results in a cis alkene Could also favor trans alkene if one uses Na or Li in NH3 (liquid) at 78C

Oxidation

MnO in H2O

4-

Carboxylic Acid RCOOH, CO2, H2O Varies depending on Substrate functional group

Oxidize an alkyne RCOOH, Oxidize an alkene ROH RCOOH Aldehye ROH Double bond breaks and an Oxygen attaches to each Carbon atom that was previously involved in the bond General Steps in SEAr: (1) benzene reacts with an electrophile forming a carbocation intermediate which is approximated by 3 resonance structures, (2) a base in the reaction mixture pulls off a proton from the carbocation intermediate and the electrons that held the proton move into the ring to establish aromaticity
+

Ozonolysis ELECTROPHILIC AROMATIC SUBSTITUTION Halogenation

O3 in Zn and H2O/Acetic acid

Benzene + Br2 Benzene + Cl2 Benzene + I2 Benzene + HNO3 Benzene + H2SO4

FeBr2 catalyst (Lewis Acid) FeCl2 catalyst (Lewis Acid) + Oxidizing Agent to transform I22I Sulfuric acid H2SO4 Fuming or concentrated sulfuric acid

Bromobenzene, HBr Chlorobenzene, HCl + Iodobenzene, I Nitrobenzene, H2O Benzenesulfonic acid, H2O

Nitration Sulfonation

Nitric acid HNO3 receives H from H2SO4, this forms H2O and NO2 One H2SO4 molecule donates one of its Hydrogen to another H2SO4 which in turn produces H2O. The second H2SO4 which is now HSO3 + donates its sole H to H2O producing H3O and SO3 Acyl: R-C=O; for FC reactions, benzene w/ amino groups dont undergo alkylation or acylation because amino group becomes a powerful electron-withdrawing group by the lewis acid Major disadvantage of FCA is that there are Carbocation rearrangements, to solve this, use acylation followed by reduction: Benzene in acylation benzene w/ R-C=O; to remove O, do another rxn where you will add H2 and use Pd as catalyst (Hydrogenation) Used to reduce acyl carbon (to reduce means to replace C=O bond with 2 C-H bonds) To form formyl chloride: CO + HCl (at high pressure) O=CH-Cl
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Friedel-Crafts Acylation

Benzene + acyl halide Benzene + acid anhydride Benzene + R-X

AlCl3 catalyst (Lewis Acid) in H2O AlCl3 catalyst (Lewis Acid) in H2O

Benzene w/ R-C=O, H-X Benzene w/ R-C=O, RCOOH

Friedel-Crafts Alkylation

AlCl3 catalyst (Lewis Acid)

Benzene-R, H-X

Clemmensen Reduction and Wolff-Kishner reduction Gatterman-Kock Formylation

Benzene w/ Acyl Benzene w/ Acyl Benzene + Formyl Chloride Nitrobenzene

Zn(Hg), HCl, heat H2NNH2, HO , heat AlCl3/CuCl3

Benzene-R Benzene-R Benzaldehyde (-COH)

Reducing a Nitro Group

Sn, HCl (use metal and HCl)

Protonated Aniline (Anilinium)

Can still be continued by reacting Anilinium ion with OH to produce aniline and H2O

Side Chain of Substituted Benzene: a. Halogenation of Alkyl side chain b. Oxidation of Alkyl side chain

Alkyl Benzene + X2

UV, Heat

Benzene-(Alkyl halide), H-X

Alkyl portion: undergoes FR substitution characteristic of alkanes + Aromatic Ring: undergoes E substitution characteristic of benzene Convert all alkyl substituents, regardless of length, into COOH

Alkyl Benzene

Hot KMnO4

Always benzoic acid

NUCLEOPHILIC AROMATIC SUBSTITUTION a. Addition Elimination Aryl halide Ar-X + OH Aryl Halide w/ 1EWG + OH Aryl Halide w/ 1EWG + OH Aryl Halide w/ 1EWG + OH
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350C, high Pressure, H2O Aq. NaHCO3, 130C Aq. NaHCO3, 100C Aq. NaHCO3, 35C

Phenol Nitrophenol Dinitrophenol Trinitrophenol