17. 1: Nomenclature: 1. In general, alcohols are named in the same manner as alkanes; replace the -ane suffix for alkanes with an -ol for alcohols CH 3CH 2CH 2CH 3 CH 3CH 2CH 2CH 2OH OH butane 1-butanol 2-butanol 2. Number the carbon chain so that the hydroxyl group gets the lowest number 3. Number the substituents and write the name listing the substituents in alphabetical order. 4. For phenols, follow benzene nomenclature and use phenol as the parent name. The carbon bearing the -OH group gets number 1.

78 OH OH OH NO2 NO2 2-methyl-2-pentanol 3-phenyl-2-butanol 3,4-dinitrophenol Many alcohols are named using non-systematic nomenclature.

OH OH H3C C OH H3C H3C OH HO OH HO OH benzyl alcohol (phenylmethanol) allyl alcohol (2-propen-1-ol) tert-butyl alcohol (2-methyl-2-propanol) ethylene glycol (1,2-ethanediol) glycerol (1,2,3-propanetriol) 79 40 17. 2: Properties of alcohols and phenols: Hydrogen bonding: The structure around the oxygen atom of an alcohol or phenol is similar to that in water and is sp3 hybridized Alcohols and phenols have much higher boiling points than similar alkanes and alkyl halides H2 O MW=18 bp= 100° C C6H6 MW=78 bp= 80° C CH3CH2CH2CH3 MW=58 bp= -0° C C6H6OH MW=94 bp= 182° C CH3CH2CH2CH2Cl MW=92.

5 bp= 77° C C6H6CH3 MW=92 bp= 110° C CH3CH2CH2OH MW=74 bp= 116° C C6H6CH2OH MW=108 bp= 203° C 80 Alcohols and phenols, like water, can form hydrogen bonds: non covalent interaction between a hydrogen atom (? +) involved in a polar covalent bond, with the lone pair of a heteroatom (usually O or N), which is also involved in a polar covalent bond (? -) O H ! – ! + O H H O H O H O H H O H H O H N H ! – ! + N H C O ! + ! C O C O H H O H O H O H H H O H H O H H H R O! ! ! H H O! R ! R O! H ! H O! R ! R O! ! H O! R.

H O H H H O H Hydrogen-bonds are broken when the alcohol reaches its bp, 81 which requires additional energy 41 17. 3: Properties of alcohols and phenols: acidity and basicity: Like water, alcohols are weak Bronsted bases and weak Bronsted acids. The nature of the R group can significantly influence the basicity or acidity H R O H + H X R O H + :X- oxonium ion R O H + H O H H R O + H O H alkoxide ion CH3CH2CH(OH)CH3 MW = 74 bp = 99° C pKa ~ 17 (CH3)C-OH MW = 74 bp = 82° C pKa ~ 18 CH3OH MW = 32 bp= 65° C pKa ~ 15.

5 CH3CH2CH2CH2OH MW = 74 bp = 116° C pKa ~ 16 The steric environment around the oxygen atom can influence the physical properties of an alcohol 82 Solvation: upon acid dissociation the alkoxide ion is stabilized by solvation through hydrogen bonding between water and the negatively charge oxygen. The steric environment around the negatively charge oxygen influences the solvation effect R O H + H O H H R O + H O H H O H O H H H H O H O H H H H O H H C H C O H C C H H H H H H O H O H H H C O H H H O.

Acidity: methanol > 1° alcohol > 2° alcohol > 3° alcohol Reflects the ability water to stabilized the resulting alkoxide 83 though solvation 42 Electronic factors that influence acidity: inductive and resonance effect CH3CH2OH pKa ~ 16. 0 FCH2 CH2 OH 14. 4 F3C F3C F3C F2CHCH2OH 13. 3 F3CCH2OH 12. 4 (F3C)3CCH2OH 5. 4 C !+ O Electron-withdrawing groups make an alcohol a stronger acid by stabilizing the conjugate base (alkoxide) -Br 9. 35 -NO2 7. 15 -CH3 10. 16 -OCH3 10. 21 -NH2 10. 46 X OH pKa ~ X= -H 9. 9 -Cl 9. 38 X OH X OH ~ pKa X= -Cl -NO2 -OCH3 -CH3 9. 38 7. 15 10. 21 10. 17 8. 85 8. 28 9. 65 10.

16 84 Phenols are much more acidic than aliphatic alcohols: a benzene ring is generally considered electron withdrawing (inductive effect) the benzene ring stabilizes the negative charge of the phenoxide ion through resonance (Fig. 17. 3, p. 595) 85 43 Electron-withdrawing substituents make a phenol more acidic by stabilizing the phenoxide ion through delocalization of the negative charge and through inductive effects Electron-donating substituents make a phenol less acidic by destabilizing the phenoxide ion (resonance effect) The location of the substituent relative to the phenol is important.

86 17. 4: Preparation of alcohols: H3O+ OH Markovnikov addition H a) B2H6, THF b) NaOH, H2O2 BR2 H OH Anti-Markovnikov Overall syn addition of H–OH across the ? -bond Markovnikov a) Hg(OAc)2, H2O b) NaBH4 OH OH HgOAc a) OsO4 b) NaHSO3 O O Os O O OH OH Syn addition of -OH groups Hydration of alkenes (Ch. 7. 4) Oxymercuration of alkenes (Ch. 7. 4) Hydroboration of alkenes (Ch. 7. 5) Di-hydroxylation of alkenes (Ch. 7. 8) 87 44 17. 5: Alcohols from reduction of carbonyl compounds Figure 10. 5 (Chapter 10. 10) Increasing oxidation state C C C C C C O C OH C O C OR CO2.

Cl Cl C Cl C Cl Cl C Cl Cl Cl C Cl Cl C NH2 C NH C N 88 17. 5: Alcohols from reduction of carbonyl compounds add the equivalent of H2 across the ? -bond of the carbonyl to give an alcohol O R C R’ [H] R R’ O C H H aldehyde (R or R? = H) > 1° alcohol ketone (R and R? H) > 2° alcohol [H]: sodium borohydride: NaBH4, ethanol reduces aldehydes to 1° alcohols and ketones to 2° alcohols lithium aluminum hydride (LAH): LiAlH4, ether reduces aldehydes, carboxylic acids, and esters to 1° alcohols and ketones to 2° alcohols In general, NaBH4 and LiAlH4 will not reduce C=C.

M O H: C EtOH or ether O C H M H3O+ OH C H 89 45 17. 6: Alcohols from reaction of carbonyl compounds with Grignard reagents Alkyl halides will react with some metals (M0) in ether or THF to form organometallic reagents Grignard reagent- organomagnesium R-X + Mg(0) ether or THF R-Mg(II)-X X= Cl, Br, or I R can be a variety of groups: 1°-, 2°-, 3°-alkyl, aryl or vinyl ! – ! + _ C C MgX Carbanions: nucleophile reacts with electrophile R-MgX ? R: – 90 Grignard reagents react with aldehydes or ketones to give alcohols MgX O R:.

C ether O C R MgX H3O+ OH C R O C !! + If, carbonyl= H2C=O > 1° alcohol = aldehyde > 2° alcohol = ketone > 3° alcohol MgBr 1) H2C=O 2) H3O+ OH Br Mg0, ether O Br Mg0, ether MgBr 1) 2) H3O+ H OH Mg0, ether CH3CH2Br CH3CH2MgBr 1) 2) H3O+ O OH 91 46 Grignard reagents react with esters to give 3° alcohols O O H3C _ CH2CH3 1) 2 H3CMgBr 2) H3O+ HO CH3 CH3 H3CMgBr the H3O+ _ O CH3 OCH2CH3 O CH3 MgX Some functional groups are incompatible with Grignard reagents Grignard reagents are very strong bases as well as highly reactive nucleophiles O R O H _ H3C MgBr R O _ O MgX + CH4 H3O+ R O OH Carboxylic acids are simply deprotonated by Grignard reagents and do not give addition products.

92 Grignard reagents will deprotonate alcohols Mg0 HO Br HO _ MgBr _ O BrMg H H3O+ HO H Other incompatible groups: -CO2H, -OH, -SH, NH2, CONHR (amides) Reactive functional groups: aldehydes, ketones, esters, amides, halides, -NO2, -SO2R, nitriles 93 47 17. 7 Some reactions of alcohols A. Reactions involving the C-O bond Dehydration to alkenes: E1 mechanism (reactivity: 3° > 2° >> 1°) requires strong acid catalyst (H2SO4) water is a much better leaving group than HOusually follows Zaitzev’s rule OH H3C C CH2CH3 CH3 H2SO4 H2O, THF H3C C C.

H3C H H3C CH3 H2C C CH2CH3 – H2O 94 Dehydration to alkenes with POCl3 E2 mechanism- requires an anti-periplanar conformation between leaving group and the hydrogen that is being lost mild conditions, requires a base (pyridine) H OH POCl3, pyridine H H CH3 CH3 H OH CH3 POCl3, pyridine CH3 H 95 48 Conversion of an alcohol to an alkyl halide (R-OH > R-X) (Chapter 10. 7) 1. Substitution reaction of alcohols with HX R-OH + HX R-X + H2 O Works better with more substituted alcohols H H Methyl H H R H C OH.