Chapter 17. Alcohols and Phenols. Alcohols and Phenols. Naming Alcohols and Phenols

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1 hapter 17 Alcohols and Phenols Alcohols and Phenols - alcohols - compounds that have hydroxyl groups bonded to saturated, sp 3 -hybridized carbon atoms - phenols - compounds that have hydroxyl groups bonded to aromatic rings - enols - compounds that have a hydroxyl group bonded to a vinylic carbon Naming Alcohols and Phenols - classified as primary (1 o ), secondary (2 o ), or tertiary (3 o ) primary (1 o ) secondary (2 o ) tertiary (2 o ) - named as derivatives of the parent alkane 1

2 ules for Alcohols 1) Select longest carbon chain containing the hydroxyl group; derive the parent name -e with -ol 2) Number the alkane chain beginning at the end nearer the hydroxyl group 3) Number substituents according to position on the chain and list substituents in alphabetical order Examples: methyl-2-pentanol cis-1,4-cyclohexanediol phenyl-2-butanol ommon Alcohols 2 benzyl alcohol allyl alcohol tert-butyl alcohol ethylene glycol glycerol Naming Phenols - phenol is both the name of the hydroxy compound and family name for hydroxy-substituted aromatic compounds 3 2 N N 2 m-methylphenol 2,4-dinitrophenol 2

3 Properties of Alcohols and Phenols - alcohols and phenols have geometry nearly the same as water - -- angle ~ 109 o - oxygen atom is sp 3 hybridized Physical Properties of Alcohols - alcohols have much higher boiling points than hydrocarbons and alkyl halides ompound Molecular Mass Boiling Point 1-propanol butane chloroethane 60 g/mol 58 g/mol 65 g/mol 97 o -0.5 o 12.5 o omparison of Boiling Points 3

4 Physical Properties of Phenols - phenols have elevated boiling points relative to hydrocarbons 3 phenol: bp = o toluene: bp = o ydrogen Bonding by Alcohols and Phenols Basicity and Acidity - alcohols and phenols are both weakly basic and weakly acidic - reversibly protonated by strong acids to yield oxonium ions, X X - dissociate slightly in dilute aqueous solution by donating a proton to water, generating 3 + and alkoxide ion -, or a phenoxide ion, Ar - : + + 4

5 Alcohols Factors Affecting Basicity and Acidity 1) solvation and steric effects - smaller substituents promote solvation of the alkoxide ion that results from dissociation methoxide ion, 3 - (pka = 15.5) t-butoxide ion, ( 3 ) 3 - (pka = 18.0) - the more easily the alkoxide ion is solvated, the more stable it is - the more stable the alkoxide ion, the more acidic the parent alcohol 2) inductive effects - electron-withdrawing substitutents stabilize an alkoxide ion by spreading the charge over a large volume, making the alcohol more acidic F 3 3 F 3 3 F 3 3 (pka = 5.4) (pka = 18.0) Generation of Alkoxides - alcohols react with alkali metals and with strong bases to form alkoxides K 3 K tert-butyl alcohol potassium tert-butoxide 5

6 Examples 3 + Na 3 - Na methanol sodium methoxide NaN Na ethanol sodium ethoxide + 3 MgBr + MgBr + 2 cyclohexanol bromomagnesium cyclohexoxide Phenols - phenols are a million times more acidic than alcohols - greater acidity is because the phenoxide ion is resonance-stabilized - delocalization of the negative charge over the ortho and para positions of the aromatic ring results in increased stability of the phenoxide anion EWG EDG - phenols with an electron-withdrawing substituent are generally more acidic since the substitutents delocalize the negative charge - phenols with an electron-donating substituent are generally less acidic since the substitutents destabilize the phenoxide ion esonance Stabilization of the Phenoxide Ion 6

7 eview Preparation of Alcohols 1) hydration of alkenes by way of hydroboration/oxidation and oxymercuration/reduction B TF B 2-3 trans-2-methylcyclohexanol 1-methylcyclohexene g(ac) gac 3 NaB 4 1-methylcyclohexanol 2) hydroxylation of an alkene with s 4 followed by reduction with NaS 3 3 s 4 pyridine 3 s NaS methyl-1,2-epoxycyclohexane 1-methylcis-1,2-cyclohexanediol g(ac) methyltrans-1,2-cyclohexanediol methylcyclohexene 7

8 eduction of arbonyl ompounds [] eduction of Aldehydes and Ketones - aldehydes are reduced to primary alcohols and ketones are reduced to secondary alcohols aldehyde [] primary alcohol ' ketone [] ' secondary alcohol eagents for Aldehyde and Ketone eduction 1. NaB 4, Et butanal 1-butanol (85%) 1. NaB 4, Et dicyclohexyl ketone dicyclohexylmethanol (88%) 1. LiAl 4, ether cyclohexanone 2-cyclohexenol - sodium borohydride NaB 4 is usually chosen because of its safety and ease of handling 8

9 eduction of arboxylic Acids and Esters or ' [] primary alcohol - carboxylic acids and esters are reduced to give primary alcohols Examples 1. LiAl 4, ether 3( 2) 7 ( 2) 7 3( 2) 7 ( 2) octadecenoic acid 9-octadecen-1-ol (87%) 1. LiAl 4, ether methyl-2-pentenoate 2-penten-1-ol (91%) - NaB 4 reduces esters slowly and does not reduce carboxylic acids; LiAl 4 reduces all carbonyl groups Mechanism - can be regarded to involve attack of a hydride ion to the positively polarized, electrophilic carbon atom of the carbonyl group carbonyl compound alkoxide intermediate alcohol - protonation by acid gives the alcohol 9

10 eactions with Grignard eagents X MgX Grignard reagent = 1 o, 2 o, or 3 o alkyl, aryl, vinylic X = l, Br, or I 1. MgX, ether MgX Formaldehyde eaction MgBr + 1. Mix cyclohexylmagnesium bromide formaldehyde cyclohexylmethanol (65%) Aldehyde eaction methylbutanal + MgBr phenylmagnesium bromide 1. ether solvent methyl-1-phenyl-1- butanol (73%) Ketone eaction cyclohexanone MgBr, ether ethylcyclohexanol (89%) Ester eaction ethylpentanoate MgBr, ether methyl-2-hexanol (85%)

11 arboxylic Acid eaction MgBr + + ' ' + MgBr carboxylic acid carboxylic acid salt - carboxylic acids do not give addition products with Grignard reagents because the acidic carboxyl hydrogen reacts with the basic Grignard reagent to yield a hydrogen carbon () and magnesium salt of the acid Limitations of Grignard eagents - Grignard reagent cannot be prepared from an organohalide if there are other reactive functional groups in the same molecule - this limits the structures of the products Br molecule FG - Grignard cannot be made where FG = = -, -N, -S, - protonate Grignard =,, N 2,, N N 2 S 2 adds to Grignard Mechanism 3 + carbonyl compound alkoxide intermediate alcohol - Grignard reagent acts as a nucleophilic carbon anion, or carbanion; the addition of the Grignard is analogous to the addition of a hydride 11

12 eactions of Alcohols - reactions - reactions Dehydration of Alcohols (- bond) a number of methods have been developed: 1) acid-catalyzed dehydration (mild) 2) acid-catalyzed dehydration (harsh) 3) phosphorus oxychloride Acid-catalyzed dehydration 3 3 +, TF 3 50 o 1-methylcyclohexanol 1-methylcyclohexene (91%) 3 3 +, TF o methyl-2- butanol 2-methyl-2-butene (trisubstituted) 2-methyl-1-butene (disubstituted) - acid-catalyzed reaction follows Zaitsev s rule, giving the more highly substituted alkene as major product - E1 mechanism that involves three steps 12

13 eactivity > > reactivity - tertiary substrates always react fastest in E1 reactions because they lead to highly stabilize tertiary carbocation intermediates Mechanism Phosphorus xychloride 3 Pl3 pyridine, o 3 1-methylcyclohexanol 1-methylcyclohexene (96%) - E2 mechanism, -Pl 2 is excellent leaving group - pyridine serves as both solvent and base 13

14 Mechanism onversion of Alcohols into Alkyl alides (- Bond) 2 Sl 2 2 l + S 2 + l 2 PBr 3 2 Br + PBr 2 - tertiary alcohols are converted using l or Br at o through an S N 1 mechanism - secondary and primary alcohols are resistant to acid and are converted using either Sl 2 or PBr 3 through an S N 2 mechanism Mechanism 14

15 onversion of Alcohols into Tosylates (- Bond) alcohol + 3 l S p-toluenesulfonyl chloride pyridine 3 S tosylate + pyridine l - reaction produces alkyl tosylates which are synthetically useful since they behave like alkyl halides - in contrast to alkyl halides, the products undergo only one Walden inversion to form a product - the product is therefore of opposite stereochemistry relative to the reactants 15

16 xidation of Alcohols oxidize reduce Primary Alcohol [] aldehyde [] carboxylic acid Secondary Alcohol ' Tertiary Alcohol [] ' ketone '' ' [] N EATIN eagents - large number of reagents can be used: KMn 4, r 3, Na 2 r 7 - depends on factors such as cost, convenience, reaction yield, and alcohol sensitivity 16

17 Preparation of an Aldehyde from a Primary Alcohol on Laboratory Scale - use of pyridinium chlorochromate (P) 2 P 2 l 2 citronellol citronellal (82%) P = N r 3 l - - most other oxidizing agents oxidize primary alcohols to carboxylic acids 3 ( 2 ) decanol r 3 3 +, acetone 3 ( 2 ) 8 decanoic acid (93%) Secondary Alcohols to Give Ketones - large scale and inexpensive, use Na 2 r 2 7 : 3 Na 2 r , 3 2, 3 3 heat 3 4-tert-butylcyclohexanol 4-tert-butylcyclohexanone (91%) - for sensitive alcohols, use P: P 3 2 l 2, 25 o testosterone 4-androstene-3,17-dione (82%) Mechanism - pathway closely related to E2 reaction r Base r chromate intermediate r Base E2 carbonyl compound - reaction produces a - bond (compare to - bond) 17

18 Protection of Alcohols - it is often necessary to circumvent synthetic incompatibilities using protecting groups 1) introduce the protecting group 2) carry out the desired reaction 3) remove the protecting group Mg Br x MgBr Ether Trimethylsilyl (TMS) ether - common protecting group for alcohols is trimethylsilyl (TMS) ether 3 3 ( 3 2 ) 3 N + 3 Si l Si 3 + ( 3 2 ) 3 N + l - 3 alcohol 3 chlorotrimethylsilane a trimethylsilyl ether Example ( 3 2 ) 3 N Si( 3 ) 3 + ( 3 ) 3 Sil cyclohexanol cyclohexyl trimethylsilyl ether (94%) 18

19 emoval of the Protecting Group - protecting group can be removed using acid or with fluoride ion Si cyclohexyl TMS ether 3 + cyclohexanol + ( 3 ) 3 Si Preparation of Phenols Dow Process l 1. Na, 2, 340 o, 2500 psi Alternative Synthesis heat cumene cumene hydroperoxide phenol acetone Mechanism 19

20 Acetal + 2 Acid catalyst ' ' emiacetal ' Laboratory Preparation S 3 S 3 2 S 4 1. Na, 300 o toluene 3 p-toluenesulfonic acid 3 p-methylphenol (72%) - owing to the harsh reaction conditions, the reaction is limited to alkyl-substituted phenols Uses of Phenols 2 l l l l l l l l pentachlorophenol (wood preservative) l l 2,4-dichlorophenoxyacetic acid (herbicide) ( 3 ) 3 3 ( 3 ) 3 l l l l 3 hexachlorophene (antiseptic) butylated hydroxytoluene (food preservative) 20

21 eactions of Phenols 1) Electrophilic Aromatic Substitution - - group is strongly activating, ortho- and para-directing - phenol is therefore highly reactive for electrophilic halogenation, nitration, sulfonation, Friedel-rafts reactions Y Y ortho- para- 2) xidation of Phenols - oxidation yields 2,5-cyclohexadiene-1,4-dione or quinone - reactions can be accomplished with Na 2 r 2 7 and (KS 3 ) 2 N (KS 3 ) 2 N 2 phenol benzoquinone (70%) eversible xidation - oxidation-reduction (redox) properties of quinones makes quinones a valuable class of compounds Snl 2, 2 Fremy s salt benzoquinone hydroquinone 21

22 Ubiquinones ( 2 2) n 3 - redox behavior is found in biology, where compounds known as ubiquinones act as biochemical oxidizing agents to mediate electron-transfer processes in the mitochondria Energy Production in the Mitochondria NAD NAD ½ NAD + ½ NAD Spectroscopy of Alcohols and Phenols Infrared Spectroscopy - alcohols characteristic - stretching absorption at cm -1 - depends upon the extent of hydrogen bonding - unassociated: sharp absorption at 3600 cm -1 - hydrogen bonds: broad absorption at cm -1 - strong - stretching band near 1050 cm -1 - phenols broad absorption at 3500 cm -1 plus aromatic bands at 1500 and 1600 cm -1 22

23 Infrared Spectrum of yclohexanol Infrared Spectrum of Phenol NM Spectroscopy - 13 NM spectra: - 1 NM spectra: 69.5 δ 35.5 δ 24.4 δ 25.9 δ - hydrogens on oxygen-bearing carbons are deshielded ( δ) - hydrogen atom of - undergoes exchange: A ' D 2 D (can exchange hydrogen for deuterium) 23

24 1 NM Spectrum of 1-Propanol Mass Spectrometry - alcohols fragment by two pathways: alpha cleavage and dehydration both fragments are apparent in mass spectra Mass Spectrum of 1-Butanol 24