《有机化学》课程教学课件（Organic Chemistry, Alex Jonathan Roche lecture notes Rutgers The State University NJ, wade 8th）Chapter 10 Synthesis and Structure of Alcohols

Synthesis and Structure of Alcohols Alcohols can be considered organic analogues of water. 108.9 1045o H HH water methyl alcohol methy!alcohol Alcohols are usually classified as primary,secondary and tertiary. H H R R OH R-OHR-OH OH H 个1 primary secondary tertiary phenol Alcohols with the hydroxyl bound directly to an aromatic (benzene)ring are called phenols Ch10 Alcohols:Struct+synth (landscape) Page 1

Ch10 Alcohols; Struct + synth (landscape) Page 1 Synthesis and Structure of Alcohols Alcohols can be considered organic analogues of water. Alcohols are usually classified as primary, secondary and tertiary. Alcohols with the hydroxyl bound directly to an aromatic (benzene) ring are called phenols. R H H OH R H R OH R R R OH primary secondary tertiary OH phenol

Nomenclature of Alcohols (Normally any compound's name which ends in-ol is an alcohol of some sort) IUPAC rules that: (1)Name the longest carbon chain bearing the-OH group.Drop the last-e from the alkane name and add-ol to obtain the root name. (2)Number the longest chain starting at the end nearest the-OH group,and designate a number for the-OH group.(Hydroxyl has greater priority than carbon-carbon multiple bonds). (3)Name the remaining substituents and their numbers as for alkanes and alkenes CH,OH CHOH CH,-C一CH-CH2-Br CHC-CH-CH:-Br CH CH 1-bromo-3,3-dimethylbutan-2-ol Chl0 Alcohols:Struct synth (landscape) Page 2

Ch10 Alcohols; Struct + synth (landscape) Page 2 Nomenclature of Alcohols (Normally any compound’s name which ends in –ol is an alcohol of some sort) IUPAC rules that: (1) Name the longest carbon chain bearing the –OH group. Drop the last –e from the alkane name and add –ol to obtain the root name. (2) Number the longest chain starting at the end nearest the –OH group, and designate a number for the –OH group. (Hydroxyl has greater priority than carbon-carbon multiple bonds). (3) Name the remaining substituents and their numbers as for alkanes and alkenes. 1-bromo-3,3-dimethylbutan-2-ol

(4)Cyclic alcohols have the prefix cyclo-,and the hydroxyl group is deemed to be on C-1. HO CH2CH3 1-ethylcyclopropanol (5)Alcohols with double or triple bonds are named using the-ol suffix on the alkene or alkyne name.Numbering gives the hydroxyl group the lowest possible number. OH (Z)-4-chlorobut-3-en-2-ol Chl0 Alcohols:Struct synth (landscape) Page 3

Ch10 Alcohols; Struct + synth (landscape) Page 3 (4) Cyclic alcohols have the prefix cyclo-, and the hydroxyl group is deemed to be on C-1. (5) Alcohols with double or triple bonds are named using the –ol suffix on the alkene or alkyne name. Numbering gives the hydroxyl group the lowest possible number. HO CH2CH3 1-ethylcyclopropanol

(6)If the hydroxyl group is only a minor part of the structure,it may be named as a hydroxy-substituent. CH,CH,OH OH 0 3 HO H CH一CH一CH2一C一OH trans-3-(2-hydroxyethyl)cyclopentanol 3-hydroxybutanoic acid Nomenclature of Diols (Gycols) Diols are compounds with two hydroxyl groups. They are named as for alcohols except the suffix-diol is used,and two numbers are required to locate the-OH's. OH OH OH OH CH,一CH一CH,OH OH IUPAC name: propane-1.2-diol I-cyclohexylbutane-1.3-diol trans-cyclopentane-1.2-diol Nomenclature of Phenols A phenol always involves a benzene (type)ring,and often the terms ortho,meta and para(meaning 1,2 disubstituted,1,3 disubstituted and 1,4 disubstituted respectively)are used.These terms are non-IUPAC though. 0 OH OH OH Br CH,CH2 IUPAC name: 2-bromophenol 3-nitrophenol 4-ethylphenol common name: ortho-bromophenol meta-nitrophenol para-ethylphenol Chl0 Alcohols:Struct +synth (landscape) Page 4

Ch10 Alcohols; Struct + synth (landscape) Page 4 (6) If the hydroxyl group is only a minor part of the structure, it may be named as a hydroxy- substituent. Nomenclature of Diols (Gycols) Diols are compounds with two hydroxyl groups. They are named as for alcohols except the suffix –diol is used, and two numbers are required to locate the –OH’s. Nomenclature of Phenols A phenol always involves a benzene (type) ring, and often the terms ortho, meta and para (meaning 1,2 disubstituted, 1,3 disubstituted and 1,4 disubstituted respectively) are used. These terms are non-IUPAC though

Solubility of Alcohols The hydroxyl groups in alcohols can form hydrogen bonds with water,and many low molecular weight alcohols are miscible with water Alcohols are more polar than hydrocarbons,and are better solvents for polar substances.(E.g.NaCl is partially soluble in Ethanol) H CH3一CH2一CH2一CH2 hydrophilic region hydrophobic region H H The Hydroxyl group is said to be hydrophilic(water loving),whereas the alkyl(hydrocarbon)end is hydrophobic (water hating). Alcohols will also dissolve in hydrocarbon solvents. Chl0 Alcohols:Struct +synth (landscape) Page 5

Ch10 Alcohols; Struct + synth (landscape) Page 5 Solubility of Alcohols The hydroxyl groups in alcohols can form hydrogen bonds with water, and many low molecular weight alcohols are miscible with water. Alcohols are more polar than hydrocarbons, and are better solvents for polar substances. (E.g. NaCl is partially soluble in Ethanol). The Hydroxyl group is said to be hydrophilic (water loving), whereas the alkyl (hydrocarbon) end is hydrophobic (water hating). Alcohols will also dissolve in hydrocarbon solvents

Acidity of Alcohols and Phenols Just like water,the hydroxyl groups in alcohols are weakly acidic-strong bases can generate alkoxide ions. R-O-H+B→R-O+B-H The acidities of alcohols vary greatly,depending on the substituents Alcohol pKa (Lower pKa is stronger acid) Methanol CH,-OH 15.5 Ethanol C,H;-OH 15.9 2-chloroethanol CI-C2H-OH 14.3 2,2,2-trifluoroethanol CFCH2-OH 12.4 t-butylalcohol (CH)C-OH 19.0 cyclohexanol C HI-OH 18.0 phenol C Hs-OH 10.0 water H-OH 15.7 acetic acid CHCO-OH 4.8 hydrochloric acid H-CI -2.2 Notice that electron withdrawing groups on an alcohol increase the acidity by stabilizing the alkoxide formed. CH3CH2-O-H H2O ±CHgCH2-0+H30*K2=1.3x1016 CF3CH2-O-H H2O -CF3CHh-O+H0*K2=4.0x1013 Chl0 Alcohols:Struct +synth (landscape) Page 6

Ch10 Alcohols; Struct + synth (landscape) Page 6 Acidity of Alcohols and Phenols Just like water, the hydroxyl groups in alcohols are weakly acidic – strong bases can generate alkoxide ions. R-O-H + B-  R-O - + B-H The acidities of alcohols vary greatly, depending on the substituents. Alcohol pKa (Lower pKa is stronger acid) Methanol CH3-OH 15.5 Ethanol C2H5-OH 15.9 2-chloroethanol Cl-C2H4-OH 14.3 2,2,2-trifluoroethanol CF3CH2-OH 12.4 t-butylalcohol (CH3)3C-OH 19.0 cyclohexanol C6H11-OH 18.0 phenol C6H5-OH 10.0 water H-OH 15.7 acetic acid CH3CO-OH 4.8 hydrochloric acid H-Cl -2.2 Notice that electron withdrawing groups on an alcohol increase the acidity by stabilizing the alkoxide formed. CH3CH2 O-H + H2O CH3CH2 O - + H3O + Ka = 1.3x 10 -16 CF3CH2 O-H + H2O CF3CH2 O - + H3O + Ka = 4.0x 10 -13

Acidity of Phenols Cyclohexanol and phenol are similar in structure,yet their acidities are very different.(Phenol is 10 more acidic). O-H +H20= +H3O* K2=1018 O-H +H20 +H30K2=1010 The phenoxide ion has resonance stabilization since the negative charge can be delocalised over 4 atoms(3 carbons and I oxygen),making it more stable. Phenols are more acidic than related alcohols. Chl0 Alcohols:Swruct +synth (landscape) Page 7

Ch10 Alcohols; Struct + synth (landscape) Page 7 Acidity of Phenols Cyclohexanol and phenol are similar in structure, yet their acidities are very different. (Phenol is 108 more acidic). The phenoxide ion has resonance stabilization since the negative charge can be delocalised over 4 atoms (3 carbons and 1 oxygen), making it more stable. Phenols are more acidic than related alcohols. O-H + H2O O - + H3O + Ka = 10 -18 O-H + H2O O - + H3O + Ka = 10 -10

Different Deprotonations of alcohols (to alkoxides) O-Na" Na*-:OH ←→ +H,O R-Q-H NaH THE R-O:Na++H21 R-O-H Na R-ONa*+2H2↑ Chl0 Alcohols:Struct synth (landscape) Page 8

Ch10 Alcohols; Struct + synth (landscape) Page 8 Different Deprotonations of alcohols (to alkoxides)

Syntheses of Alcohols Previously seen: Nucleophilic substitution of alkyl halide with HO Acid catalyzed hydration of alkenes Oxymercuration-demercuration Hydroboration-oxidation (anti-Markovnikov) Hydroxylation gives diols(syn-OsO:anti-epoxidation-hydrolysis) Acetylides and carbonyl compounds Organometallic Reagents for Alcohol Synthesis When a compound has a covalent bond between a carbon and a metal,it is called an organometallic compound. The two most common types of organometallic are Grignard reagents and organolithium reagents(although there are a variety of others,Cu,Cd,Zn,Hg,etc). C-M bond Electronegativities C世Li Li 1.0 C2.5 88 Na 0.9 Mg 1.3 A11.6 C±Mg K 0.8 86 2013 Pearson Education,Ino A carbon metal bond is polarized with significant negative charge on the carbon because metals are so electropositive These compounds will have nucleophilic carbon atoms. Chl0 Alcohols:Struct +synth (landscape) Page 9

Ch10 Alcohols; Struct + synth (landscape) Page 9 Syntheses of Alcohols Previously seen: Nucleophilic substitution of alkyl halide with HO￾Acid catalyzed hydration of alkenes Oxymercuration-demercuration Hydroboration-oxidation (anti-Markovnikov) Hydroxylation gives diols (syn – OsO4 : anti – epoxidation-hydrolysis) Acetylides and carbonyl compounds Organometallic Reagents for Alcohol Synthesis When a compound has a covalent bond between a carbon and a metal, it is called an organometallic compound. The two most common types of organometallic are Grignard reagents and organolithium reagents (although there are a variety of others, Cu, Cd, Zn, Hg, etc). A carbon metal bond is polarized with significant negative charge on the carbon because metals are so electropositive. These compounds will have nucleophilic carbon atoms

Grignard Reagents These are of the formal type R-Mg-X. CHCH,OCH,CH 6 R-X+Mg R-Mg-X reacts like R:MgX (X=CI.Br,or I) organomagnesium halide (Grignard reagent) They are made via the reaction of metallic Mg with the corresponding alkyl halide,usually in ether type solvents. This reaction is versatile;primary,secondary and tertiary alkyl halides can be used,and also vinyl,allyl and aryl halides. Mg Mg- Ether Mg HgC-Br HaC-Mg-Br Ether Organolithium Reagents These are also formed via action of the metal with an alkyl halide R-X 2Li →Lit-X+R一Li reacts like R:Li (X CI.Br,or I) organolithium Unlike Grignard reagents,alkyl lithiums can be prepared and used in a variety of hydrocarbon solvents(hexane, pentane etc). Chl0 Alcohols:Struct +synth (landscape) Page 10

Ch10 Alcohols; Struct + synth (landscape) Page 10 Grignard Reagents These are of the formal type R-Mg-X. They are made via the reaction of metallic Mg with the corresponding alkyl halide, usually in ether type solvents. This reaction is versatile; primary, secondary and tertiary alkyl halides can be used, and also vinyl, allyl and aryl halides. Organolithium Reagents These are also formed via action of the metal with an alkyl halide. Unlike Grignard reagents, alkyl lithiums can be prepared and used in a variety of hydrocarbon solvents (hexane, pentane etc). I H3C Br Mg Ether Mg-I Mg Ether H3C Mg-Br