hapter 10 Alcohols and Ethers Alcohols (醇) (E)-6,7-二甲基-6-壬烯-1-醇 (E)-6,7-dimethyl-6-nonen-1-ol 1-甲基环戊醇 1-methylcyclopentanol 10.1 Nomenclature, lassification and Structure 10.1.1 Nomenclature 2 (2,5S)-7-甲基-2,5-辛二醇 (2,5S)-7-methyl-2,5-octanediol 10.1.2 lassification primary alcohols(伯醇, 1º醇) secondary alcohols(仲醇, 2º醇) tertiary alcohols(叔醇, º醇) ' 10.1. Structure sp 22 2 ' 2 22l 2 22 2 l 2-苯基-2-丙醇 2-phenyl-2-propanol 苯甲醇 苄醇 phenylmethanol 22 4-羟甲基-1,8-辛二醇 4-hydroxymethyl-1,8-octanediol 2 环戊基甲醇 cyclopentylmethanol (1,4)--2-环己烯-1,4-二醇 (1,4)-cyclohex-2-ene-1,4-diol (1S,2S)-2-甲基环己醇 (1S,2S)-2-methylcyclohexanol 5,6,6-三甲基-5-乙基-2-庚醇 5-ethyl-5,6,6-trimethyl-2-heptanol Ph overtone 10.2 Spectroscopy(光谱学) sp I(红外) sp2 醇 伸缩振动: 游离羟基650 610(尖峰, 强度不定), 缔合羟基500~00 (宽峰) (形成氢键后基团的伸缩频率都会下降 谱带变宽) 醇-伸缩振动1260~1000 2 ring - Mono Subst. Ph 75 & 697 cm-1 22222 1-己醇 1
NM(核磁共振氢谱) 羟基质子δ=0.5~5.5ppm 氢键使羟基质子共振信号移向低场, 常是一个较宽的单峰 分子内氢键, 其化学位移变化与溶液浓度无关 加入几滴重水(D2), 再测定图谱 会使羟基质子信号消失 -2- (a) ydrogen-bonded - only (neat liquid) (b) Free and ydrogen-bonded - (dilute solution) (c) Free and ydrogen-bonded - (very dilute solution) MS(质谱) 10. eactions 醇的分子离子峰M经常较弱, 甚至看不到, M-18或M-15或M-29峰丰 度较高 Acidity and basic / nucleophilic δ SN2 or SN1 - is a leaving group (very poor) δ 2 δ E1 or E2 Formation of esters(酯) and sulfonates(磺酸酯) xidation 10..1 Acidity and Basic / Nucleophilic Acidity 2 = 2 - Alkoxide ion (stablized by solution) m/z = 118 m/z = 16 Acidity: 1º >2º >º 2 m/z = 107 Acidity: S > > Ar > 2 > > > 2 > N > eaction with active metals(与活泼金属反应) K Na Mg Al Na 2 Na 亲核试剂 强碱 Na 2 Na 2N > > 2N > l l > > > ()2 Al [()2]Al () K ()K 大体积强碱 亲核性较弱 Good leaving group Basic / Nucleophilic Na 2 Na N Na Na Na NaN2 NaN2 Na N 'MgX ' MgX() A A质子化醇 盐 I 2 I- BF BF- 55 ()25 2 叔卤代烷的溶剂解(SN1), 醇的亲核性弱 72% 28% () 25 2
10..2 Formation of esters and sulfonates ', (') 2 or 'l ' 羧酸酯酰基化反应 N 2 N 2 N 2 N 2 N 2 2 N 2 三硝酸甘油酯 P P Pl () P N 硝酸酯 亚硝酸酯 P P N 2 硝基化合物 磷酸酯 Sulfates( 硫酸酯 ) S S S () 2 S 2 2 S 4 Me 2 S 4 硫酸二甲酯是个很好的甲基化试剂 S base 2 S 2 S N 2 Sulfonates( 磺酸酯 ) 'S 2l base S 'S 2 l 2 Msl S Pl 5 S l Pl l S l 2 Tsl base base S 2 MsEt S 2 TsEt ' l Ts retention -l 'S 2 磺酸酯是个很好的烷基化试剂 ' S ' S 2 - N 2 Nu 2 Nu ' S 常用亲核试剂 : 烷氧基负离子, 卤素负离子等 S 2 2 5 Na 2 5 Ts - 10.. Nucleophilic Substitution( 亲核取代 ) Nu - Nu - is a leaving group (very poor) 10...1 eaction with X X X eactivity of X I > > l Na 2 S 4 KI P 4 eactivity of Benzyl, allyl, º > 2º > 1º 用 Lucas 试剂鉴别各类醇 叔醇易消除, 故低温 Nu - ' Ts inversion S N 2 Nu ' - Ts l (concd) 25 o 94% 2 2 2 (concd) reflux l 2 2 2 2 (95%) Mechanism 1 alcohols and methanol S N 2 2 X - X Znl 2 - Znl 2 - l - Znl 2 l [Zn()l 2 ] - 2,, allylic, and benzylic alcohols S N 1 slow l - fast fast l 外消旋化 E1 重排
Neighboring-group Participation( 邻基参与 ) 10...2 eaction with ther eagents 苏式 苏式外消旋体 PX 或 PX 5 P 2 5 P 2 5 Pl 5 l l Pl 2 5 P I 2 I 2-1 and 2 alcohols seldom rearrangement(s N 2) - 2 P 2 P 2-2 P 2 2 P 2 A good leaving group ( ) 2 2 P -10 to 0 o 4 h ( ) 2 2 (55-60%) Sl 2 ( 亚硫酰氯氯化亚砜 ) reflux Sl 2 l l S 2 1 and 2 alcohols seldom rearrangement 2 l S l l 2 S - l S N i retention of configuration -l 2 pyridine Sl 2 l 2 S 2 l l - -S 2 S 2 2 l 紧密离子对 A amine is added to promote the reaction inversion of configuration (S N 2) 10... eactions via Sulfonates or Sulfates( 通过磺酸酯或硫酸酯反应 ) Nu Tsl - N - S Nu I - / 丙酮 - 构型保持构型翻转 S 碱 10..4 Elimination Intermolecular Dehydration of Alcohols ( 消除反应 醇的分子内脱水 ) E1 A heat 2 (91%) Tsl Ts 10..5 xidation( 氧化 ) 2 [] ' [] t-buk [] ' 10..5.1 KMn 4 and Mn 2 2 KMn 4 2 2 K heat 2 KMn 4 74% 伯醇分子中如有烯键, 亦可被氧化仲醇叔醇用酸性高锰酸钾氧化易使碳链断裂 Mn 2 新制 Mn 2 KMn 4 MnS 4 Na Mn 2 K 2 S 4 Na 2 S 4 2 Mn 2 Mn 2 其他羟基以及烯键不受影响 4
10..5.2 hromic acid( 铬酸 ) 烯键不受影响 Na 2 r 2 7 / 2 S 4, r /Ac, r. 2Py/ 2 2 l (Sarrett 试剂 ), r. Py. l/ 2 l 2, r / 2 S 4 acetone (Jones 试剂 ) pyridinium chlorochromate P 铬酸氧化的机理 Na 2 r 2 7 / 2 S 4 Na 2 2 r 2 7 / 2 S 4 Na 2 r 2 7 / 2 S 4 2 如果醛的沸点低, 可蒸出避免进一步氧化 2 2 Na 2r 2 7 / 2 S 4 2 50% 10..5. Nitric acid( 硝酸 ) 10..5.4 ppenauer xidation 2 不影响双键对酸不稳定的基团不受影响 (i-pr) Al 可逆反应 (i-pr) Al (t-bu) Al 10..5.5 Pfizner-Moffatt xidation S D N N N,N'-dicyclohexylcarbodiimide N,N - 二环己基碳二亚胺脱水剂, 尤用于肽的合成 S S 2 N 2 2 N D N N 10.4 eactions of Glycols( 邻二醇的反应 ) Vicinal Diols 10.4.1 xidative leavage( 氧化断裂 ) 高碘酸或醋酸铅 Periodic acid( 高碘酸 ) Lead acetate ( 醋酸铅 ):Pb(Ac) 4 10.4.2 Pinacol earrangement Mechanism Mechanism I I 2 邻二醇 ( α- 二醇 ), α- 羟基醛 / 酮 / 酸, α- 氨基醛 / 酮 / 酸, 1,2- 二酮 (α- 二酮 ), 1- 氨基 -2- 羟基化合物 5
Ph Ph Ph 1) 形成最稳定的碳正离子 Ph 2) 提供电子的基团发生迁移 Ph Ph Ph Ph 10.5 Preparation of Alcohols Alkenes Alkyl alides Alcohols arbonyl ompounds ) 迁移基团与离去基团应处于反位 2 Grignard Synthesis - 2 2 10.5.1 Via ydrolysis of Alkyl alides( 通过卤代烃的水解 ) X - X - It is rarely used for the synthesis of alcohols, since alkyl halides are normally prepared from alcohols. s s Na 2 2 2, or - 10.5.2 Via eactiontion of Alkenes( 通过烯烃反应 ) 2 S 4 2 S 1) B 2) 2 2 / - Mn Mn 2 not very effective 2 several steps Mn 2 X 2 / - X xymercuration-demercuration of alkenes( 烯烃的羟汞化 - 去汞化 ) gac 2 NaB 4 g(ac) 2 还原 The reactions take place very rapidly at room temperature. The overall reaction gives alcohols in very high yields, usually greater than 90% earrangements of the carbon skeleton seldom occur. Mercury compounds are extremely hazardous. Mechanism( 机理 ) Acg g( ) 2 g 2 NaB 4 - - - Markovnikov addition anti addition ( 反式加成 ) 10.5. Via eduction of arbonyl ompounds or Derivatives of arboxylic ompounds ( 通过羰基化合物或羧酸衍生物还原 ) ' ' [ ] [ ] [ ] [ ] 2 ' 2 2 ' ydrogenation ( 2 with aney nickel): Also reduces any = bonds Sodium in alcohol Lithium aluminum hydride (LiAl 4 ): reduces acids, esters, aldehydes, and ketones Sodium borohydride (NaB 4 ): reduces only aldehydes and ketones 6
10.5.4 Grignard Synthesis( 格氏试剂合成法 ) MgX Mechanism 1. ether MgX 2 2. X - MgX Mg 2 X - - Mg 2 X - X - 1) Grignard eagents eact with Formaldehyde to Give a 1º Alcohol. 2) Grignard eagents eact with All ther Aldehydes to Give 2º Alcohols. ) Grignard eagents eact with Ketones to Give º Alcohols. 4) Esters eact with Two Molar Equivalents of a Grignard eagent to Form º Alcohols. 5) eactions of Grignard eagents with Epoxides 2 etrosynthetic Analysis ( 逆合成分析 ) 6 5 2 6 5 Mg 2 2 1. Et 2 2. N 4 l 2 6 5 2 Mg 2 2 Mg 2 6 5 1. Et 2 2. N 4 l 2 1. Et 2 2. N 4 l 2 -Phenyl--pentanol 2 2 2 6 5 6 5 6 5 2 2 2 Ethers ( 醚 ) 10.6 Structure, lassification and Nomenclature 10.6.1 Structure 111.7º sp 10.6.2 lassification -- simple ether( 单醚 ), symmetrical ether( 对称醚 ) -- complex ether( 混醚 ), unsymmetrical ether( 不对称醚 ) aliphatic ether( 脂肪醚 ) aromatic ether( 芳香醚 ) cyclic ether( 环醚 ) Epoxide, oxirane( 环氧化合物, 环氧乙烷 ) rown ether( 冠醚 ) -- 2 -- 2 Dimethyl ether Diethyl ether p-π 共轭 121º sp 2 10.6. Nomenclature ommon Names -- 甲醚 dimethyl ether methyl ether -- 2 甲乙醚 二乙烯基醚 2 -- 2 l 乙基氯甲基醚 6 5 6 5 二苯基醚 甲基叔丁基醚 IUPA Names 2- 甲基 -2- 甲氧基丙烷 2-methoxy-2-methylpropane alkoxy group -- 2 2 Epoxide, oxirane( 环氧化合物, 环氧乙烷 ) 1 2 环氧乙烷氧化乙烯 2,2- 二甲基环氧乙烷氧化异丁烯 1- 甲氧基丙烷 2- 异丁氧基丁烷 2-(2- 甲基丙氧基 ) 丁烷 2-isobutoxybutane (S)-2,2- 二甲基 -- 异丙基环氧乙烷 异丁基仲丁基醚 烯丙基乙炔基醚 甲基环己基醚 苯乙醚 7
2 1 1,2- 环氧丙烷 1 2 4 5 2,4- 二甲基 -2,- 环氧戊烷 2 1 1,- 环氧丙烷 2 1 2- 甲基 -1,2- 环氧丙烷 2,,4- 三甲基 -,4- 环氧 -1- 戊烯 1,2- 环氧环己烷 10.7 Spectroscopy I 醚 伸缩振动 1275~1020cm -1 ( 强吸收 ) 18- 冠 -6 NM 1 -- δ=.5~4ppm 2 2 2 2 MS 醚的分子离子峰 M 常较弱, β- 裂解产生丰度较高的碎片离子峰, 亦有 α - 裂解 m/z=57 分子离子失去 4 9. 2 2 2 2 2 2 M=10 10.8 eactions 10.8.1 Autoxidation( 自动氧化 ) 10.8.2 Basidity 形成钅羊盐和络合物的能力 : > Ar > ArAr ' ' - BF BF ' ' m/z=87 分子离子失去 7. 8
_ 10.8.4 Acid-atalyed leavage ' X X ' X 'X eactivity: I > >> l Ethers with 1º alkyl groups react by an S N 2 Alcohol is protonated, halide attacks, and another molecule of alkyl bromide is formed Allylic, benzylic, and o ethers cleave via E1/S N 1 2 2 2 2 混醚 - 断裂次序 : Allyl, benzyl, 烷基 >2 烷基,1 烷基, > 芳基 ArAr 在 I 作用下醚键不断裂 10.8.5 ydrogenolysis of Benzyl Ethers( 苄基醚的氢解 ) 2 2 / Pd- This eaction is useful for synthesis Protection of - 10.8.6 ing pening of Epoxide ( 环氧乙烷的开环 ) Under conditions of acid catalysis Nu - anionic nucleophile ing pening in Base Na S N 2 - - 'Na ' NaN N NaN N - 6 5 Li 6 5 ' Na ' 'MgX ' LiAl 4 N N 2 ing pening in Acid / 2 / ' N X ' N X / 6 5 6 5 B 2 6 2 B o carbocation δ 2 δ The reaction is S N 1 like 10.9 Preparation 10.9.1 Acid-atalyzed Intermolecular Dehydration of Alcohols If temperature is too high, alkene forms. - 2 2 S 4 180 o 2 2 2 1º alcohols S N 2 2 S 4 2 2 2 o and o alcohols E1 140 o S 2 2 2 2 2 2 2 2 2 2 9
10.9.2 The Williamson Synthesis of Ethers 10.9.5 Preparation of Epoxides( 环氧化合物的制备 ) - Na ' L ' S N 2, primary or secondary alkyi L=, I, S 2, S 2 Epoxidation of alkenes 10.9. Acid-catalyzed Addition of Alcohols to Alkenes 2 S 4 2 2 2 protecting group 10.9.4 Alkoxymercuration of Alkenes( 烯的烷氧汞化 ) g( NaB 4, - 2 F ) 2 /TF- g 2 F Base-promoted ring closure of vicinal halohydrins( 碱促进下 β - 卤代醇的环合 ) / 2 Na Na 2 mesomer 分子内 S N 2 racemate racemate SUMMAY Alcols Nomenclature eactions Preparation Ethers Nomenclature eactions Preparation 10