有机化学 Chapter 15 Alcohols,Diols,and Thiols.ppt

1、Chapter 15 Alcohols,Diols,and Thiols,烷烃分子中的氢原子被羟基取代后的化合物，称为醇。 烷烃分子中一个氢原子被羟基取代的，称一元醇，用 ROH表示；几个氢被取代的，称多元醇。 羟基所连接的碳原子 为一级碳原子，称为一级醇（伯醇）； Primary alcohol 为二级碳原子, 称为二级醇（仲醇）； Secondary alcohol 为三级碳原子, 称为三级醇（叔醇） Tertiary alcohol,15.1 Sources of Alcohols,工业来源 从醇能制得其他各种脂肪族化合物：烯烃、卤代烷、醚、醛、酮、酸、脂以及其他化合物。 从卤代烷，可制

2、得格氏试剂和醛、酮又可制得复杂的醇，如此等等。 醇不仅可用作原料，往往还可用醇作为反应时的溶剂和产物复结晶时的溶剂。 醇之所以在脂肪族化学中成为如此重要的原料，不仅仅是由于醇能进行多种多样的反应，还由于价格便宜，有大量供应。一些简单的醇，是有机合成的基础，借两种主要的方法得到： 通过石油裂化所得的烯烃的水合作用， 碳水化合物的发酵。 除这两种主要方法外，还有其他一些方法，但应用较少,15.1.1 烯烃的水合作用,四或五个碳原子的烯烃可以从石油裂化所得的混合物中分离出来。烯烃通过直接和水加成或硫酸加成再水解，很容易转变为醇。 用这个方法只能得到按Markovnikov法则而形成的醇。例如 可以得

3、到异丙醇，而得不到正丙醇； 可以得到仲丁醇，而得不到正丁醇； 可以得到叔丁醇，而得不到异丁醇。 用这个方法所得到的伯醇只有乙醇。,15.1.2 碳水化合物的发酵,用酵母使糖发酵，是人类所用的最古老的化学合成法，但对于制乙醇和其它一些醇至今仍是极为重要的。 糖的来源广泛，主要来源于甘蔗的糖浆，或各种谷物的淀粉；英文中谷物叫grain,因此乙醇也称作“ grain alcohol”. 当淀粉作原料时，除得到乙醇外，还得到数量较少的杂醇油（英文fusel oil,来自德文Fusel,劣等酒），它是伯醇的混合物：大部分是异戊醇，还含有正丙醇、异丁醇和2-甲基-1丁醇，即所谓旋光性戊醇。,15.2 Ov

4、erview of Preparation of Alcohols,Hydrations of Alkenes,Oxymercuration- Demercuration (羟汞化) of Alkenes,Hydroboration- Oxidation of Alkenes,Hydrolysis of Alkyl Halides,Organometallic with Aldehydes and Ketones,Organometallics with Easters,Reductions of Aldehydes and Ketones,Reductions of Easters,Redu

5、ctions of Carboxylic Acids,Opening Epoxides,15.3 Hydration of Alkenes,Reaction type: Electrophilic Addition,Summary,When treated with aq. acid, most commonly H2SO4, alkenes form alcohols. Regioselectivity predicted by Markovnikovs rule Reaction proceeds via protonation to give the more stable carboc

6、ation intermediate. Not stereoselective since reactions proceeds via planar carbocation,15.4 Hydroboration / Oxidation of Alkenes,Reaction type: Electrophilic Addition,Reagents (two steps),BH3 or B2H6 then NaOH/ H2O2,Summary,Regioselectivity : Anti-Markovnikov, since the B is the electrophile. Stere

7、oselectivity : Syn since the C-B and C-H bonds form simultaneously from the BH3. The alcohol is formed over a series of steps involving the B center , with retention of configuration at the C., 15.5 Oxymercuration-Demercuration (羟汞化) of Alkenes,Reaction type: Electrophilic Addition,Overall transform

8、ation : C=C to H-C-C-OH Typical reagents are mercury acetate, Hg(OAc)2 in aqueous THF,Mechanism for Reaction of Alkenes With Hg(OAc)2 / H2o,Step 1: The p electrons act as the nucleophile with the electrophilic Hg and loss of an acetate ion as a leaving group, forming the mercurinium ion.,Step 2: Wat

9、er functions as a nucleophile and attacks one of the mercury substituted carbons resulting in cleavage of the C-Hg bond.,Step 3: The acetate ion functions as a base deprotonating the oxonium ion to give the alcohol. This completes the oxymercuration part of the reaction.,Step 1,Step 2,Step 3,Step 4:

10、(mechanism not shown) The hydride reduces the Hg off, creating a C-H bond while breaking the C-Hg bond. This is the demercuration part of the process.,Step 4,Regioselectivity predicted by Markovnikovs rule (most highly substituted alcohol) Reaction proceeds via the formation of a cyclic mercurinium

11、ion (compare with bromination of alkenes) The mercurinium is opened by the attack of water to complete the oxy-mercuration Demercuration is effected by a reduction using sodium borohydride, NaBH4,Summary,15.6 Synthesis of Alcohols Using Grignard Reagents,The principals synthetic application of Grign

12、ard reagents is their reaction with certain carbonyl-containing compounds to produce alcohols.,Reaction usually in Et2O followed by H3O+ work-up. 若用水，则生成的Mg(OH)X为胶状物，难以处理。通常用稀酸(HCl,H2SO4)处理,Alkoxymagnesium halide,15.6.1 The substituents on the carbonyl dictate the nature of the product alcohol,Addit

13、ion to methanal (formaldehyde) gives primary alcohols,Addition to other aldehydes gives secondary alcohols.,Addition to ketones gives tertiary alcohols,Reactions of RMgX with Esters,Carboxylic esters, RCO2R, react with 2 equivalents of organolithium or Grignard reagents to give tertiary alcohols,The

14、 tertiary alcohol contains 2 identical alkyl groups,与甲酸酯反应，产物为仲醇,Reactions of RMgX with Epoxides,Ring strain makes epoxides more reactive than simple ethers,Organolithium or Grignard reagents react with the carbonyl group, C=O, in aldehydes or ketones to give alcohols. Addition to methanal (formalde

15、hyde) gives primary alcohols. Addition to other aldehydes gives secondary alcohols. Addition to ketones gives tertiary alcohols. The acidic work-up converts an intermediate metal alkoxide salt into the desired alcohol via a simple acid base reaction.,Summary,Step 1: The nucleophilic C in the organom

16、etallic reagent adds to the electrophilic C in the polar carbonyl group, electrons from the C=O move to the electronegative O creating an intermediate metal alkoxide complex. Step 2: This is the work-up step, a simple acid/base reaction. Protonation of the alkoxide oxygen creates the alcohol product

17、 from the intermediate complex.,15.6.2 The mechanism of Nucleophilic addition of RMgX to an aldehyde,Step 1,Step 2,15.6.3 Grignard 合成的限制,1， Grignard试剂的活性较高，应注意它在使用上的限制。在设计合成中，选择用于制取Grignard试剂的卤代物时, 酸，水，醇等含活泼氢的官能团可从Grignard试剂中取代出一个非常弱的酸，形成烷烃。 2，同样，任何化合物其中氢接在电负性元素氧，氮，硫或者甚至叁键碳上时都有足够的酸性去使Grignard试剂分解。一个

18、Grignard试剂能同氧、二氧化碳以及各种含有碳一氧或碳氮多键的化合物很快的反应。,用包含和 Grignard 试剂作用的基团（如,OH,-NH2）诸如HOCH2CHBr之类)的化合物来制备Grignard试剂,每当有Grignard试剂的分子形成，它立刻同另一分子中的活性基团(OH)作用, 产生不希望要的产物(HOCH2CH2H). 在制备芳基卤化镁时要特别注意，因为苯环上可能有许多别的取代基: 羧基（COOH）、羟基（OH）、氨基（NH2）以及SO3H都含有连在氧或者上的氢，因此它们有足够的酸性能使Grignard试剂分解。它对COOR以及CN基团起类似的加成。 硝基（NO2）会氧化Gr

19、ignard试剂。,归结起来, 在制备Grignard试剂时，卤代物分子中只能带有少数一些基团，其中包括R、AR、OR和Cl（卤代芳香烃中的）。 Grignard试剂作用的醛或其它化合物中也不能包含对Grignard试剂有作用的基团。 也许这些限制过于严格，但实际上令人满意的组合的数目非常之多，因此Grignard试剂依然是最有价值的合成手段之一。 在任何有机合成中都必须注意： 不应把注意力局限于我们所关心的基团，也应该考虑其它官能团可能产生的干扰。,在制备Grignard试剂及和如醛之间的反应中. 首先，卤代烃、醛以及用作试剂的醚必须小心地干燥和除去醇，因为它们都很可能是从醇制得的。有水存在

20、时，Grignard试剂几乎无法形成。 在开始实验以前，仪器必须完全干燥。 必须使反应系统避免与空气中的水气、氧和二氧化碳接触：用氯化钙管能隔绝水气，可用干燥的氮气流将氧和二氧化碳从系统中赶走。,15.7 Synthesis of Alcohols Using Organolithium Reagents,Organolithium reagents react with carbonyl groups in the same way that Grignard reagents do.,In their reactions with aldehydes and ketones, organo

21、lithium reagents are somewhat more reactive than Grignard reagents.,15.8 How to Plan a Synthesis.,The ideas collected here are based on the work of E.J.Corey (Nobel Prize 1990) who was one of the pioneers at trying to design strategies for the synthesis of complex organic molecules,Retrosynthesis me

22、ans planning a synthesis backwards, by starting at the product, the target and taking it back a step at a time to simple, available starting materials or precursors. thinking backwards, it requires good problem solving skills, and a good knowledge of their organic reactions. In order to plan a synth

23、esis, we can break the target down by making a series of disconnections - these steps are the reverse of synthetic steps or reactions,Lets look at a generic example. how could we prepare the following system ?,Scenario 1 Lets first consider disconnecting the R group by breaking the C-C bond at the f

24、unctional group.,This would correspond to the reaction of an organometallic reagent (which is equivalent to the carbanion, R-) with methanal (which has an electrophilic C),Scenario 2 Alternatively we could disconnect an H atom by breaking a C-H bond at the functional group.,This would correspond to

25、the reaction of a reducing agent such as lithium aluminum hydride with an aldehyde:,How to synthesize TM 4?,Synthesis:, 15.10 Spectrum of Alcohols,IR Spectra,NMR Spectra,15.11 Reaction of Alcohols with Hydrogen Halides,Reaction type: Nucleophilic Substitution (SN1 or SN2),When treated with HBr or HC

26、l alcohols typically undergo a nucleophilic substitution reaction to generate an alkyl halide (HX)and water(H2O).,Review: Nucleophilic Substitution Reactions,There are two fundamental events in these substitution reactions: formation of the new bond to the nucleophile breaking of the bond to the lea

27、ving group,Depending on the relative timing of these events, two different mechanisms are possible:,Bond breaking to form a carbocation preceeds the formation of the new bond : SN1 reaction Simultaneous bond formation and bond breaking : SN2 reaction,15.11.1 SN1 Mechanism,SN1 indicates a substitutio

28、n, nucleophilic, unimolecular reaction, described by the expression rate = k R-LG This pathway is a multi-step process with the following characteristics: step 1: rate determining (slow) loss of the leaving group, LG, to generate a carbocation intermediate, then step 2: rapid attack of a nucleophile

29、 on the electrophilic carbocation to form a new s bond The Effect of R- in SN1 reactions of alcohols: Reactivity order : (CH3)3C- (CH3)2CH- CH3CH2- CH3-,In an SN1, the nucleophile attacks the planar carbocation. Since there is an equally probability of attack on either face there will be a loss of s

30、tereochemistry at the reactive center and both possible products will be observed.,Stereochemistry of SN1,Notice that the products are mirror images.,SN1 Mechanism For Reaction Of Alcohols With HBr,Overall Reaction:,Step 1: An acid/base reaction. Protonation (质子化作用,加质子作用)of the alcoholic oxygen to m

31、ake a better leaving group. This step is very fast and reversible. The lone pairs on the oxygen make it a Lewis base. Step 2: Cleavage of the C-O bond allows the loss of the good leaving group, a neutral water molecule, to give a carbocation intermediate. This is the rate determining step (bond brea

32、king is endothermic) Step 3: Attack of the nucleophilic bromide ion on the electrophilic carbcation creates the alkyl bromide,重排扩环,扩环重排：五员环张力或减小，故可由叔碳正离子重排成五员环上的仲碳正离子,15.11.2 SN2 mechanism,SN2 indicates a substitution, nucleophilic, bimolecular reaction, described by the expression rate = k Nu R-LG

33、This pathway is a concerted process (single step) as shown by the following reaction coordinate diagrams, where there is simultaneous attack of the nucleophile and displacement of the leaving group,The Effects of R- in SN2 reactions of alcohols: Reactivity order : CH3- CH3CH2- (CH3)2CH- (CH3)3C-,Ste

34、reochemistry of SN2,When the nucleophile attacks in an SN2, it is on the opposite side to the position of the leaving group. As a result, the reaction will proceed with an inversion of configuration.,The Reaction of Primary Alcohols with Hydrogen Halides,伯醇与HX反应必须加热，或在其他条件协同下进行(SN2历程为主) . Catalysts:

35、 H2SO4, H3PO4,Mechanism:(SN2),Catalysts: H2SO4, H3PO4,The reaction of alcohols with HCl in the presence of ZnCl2 (catalyst) forms the basis of the Lucas test for alcohols.,15.11.3 Lucas Reagent: ZnCl2 + C. HCl,Alcohol relative reactivity order : 3o 2o 1o methyl.,Lucas test: 用于鉴别伯，仲，叔醇。 及氯代烷的制备(可避免发生

36、重排) 现象： C6以下醇可溶于Lucas 试剂，相应的氯代烷则不溶 当氯代烷从溶液中分离出来时所呈现的混浊，表示醇变成了氯代物； 而混浊出现所需的时间则是醇反应性的一种量度,1 2 3 ,ROH,ZnCl2 + C. HCl,室温下不反应 5分钟内反应 立即反应（出现混浊）,15.11.4 Reaction of Secondary Alcohols with Hydrogen Halides,将干燥的卤化氢气体通入仲醇中既可转变为相应的卤代烃历程：并可能发生重排,未发生重排的产物比例相近，说明重排前后碳正离子稳定性相近，重排速度同它与溴离子结合速度相差不多。,Rearrangement,R

37、earrangement,Rearrangement,Summary,Alcohol relative reactivity order : 3o 2o 1o methyl Hydrogen halide reactivity order : HI HBr HCl HF (paralleling acidity order).,Reaction usually proceeds via an SN1 mechanism which proceeds via a carbocation intermediate, that can also undergo rearrangement. Meth

38、anol and primary alcohols will proceed via an SN2 mechanism since these have highly unfavourable carbocations. The reaction of alcohols with HCl in the presence of ZnCl2 (catalyst) forms the basis of the Lucas test for alcohols.,15.12 Other Methods for Converting Alcohols to Alkyl Halides,Reaction o

39、f Alcohols with other Halogenating agents (SOCl2, PX3); Nucleophilic Substitution (SN1 or SN2),Thionyl(亚硫酰) chloride,81%,82 %,15.12.1 Thionyl chloride: SOCl2,2-Ethyl-1-butanol,1-Chloro-2-ethylbutane,2-Octanol,15.12.2 Phosphorous Tribromide: PBr3,Phosphorus acid is water-soluble and may be removed by

40、 washing the alkyl halide with water or with dilute aqueous base.,Phosphorous acid,Isobutyl alcohol,Isobutyl bromide,Cyclopentanol,Cyclopentyl bromide,Mechanism: SN2,The overall reaction,15.12.3 Alkyl Iodide,碘代烷可由醇与碘和红磷一起加热制备：,Alcohols can also be converted to alkyl chlorides using thionyl chloride,

41、 SOCl2, or phosphorous trichloride, PCl3. Alkyl bromides can be prepared in a similar reaction using PBr3. Used mostly for 1o and 2o ROH In each case a base is used to mop-up the acidic by-product. Common bases are triethylamine, Et3N, or pyridine, C6H5N. In each case the -OH reacts first as a nucle

42、ophile, attacking the electrophilic center of the halogenating agent. The advantage of these reagents is in that the reaction is not under the strongly acidic conditions like using HCl or HBr.,Summary,15.13 Dehydration of Alcohols,Reaction type: 1,2- or b-Elimination,When heated with strong acids ca

43、talysts (most commonly H2SO4, H3PO4), alcohols typically undergo a 1,2-elimination reactions to generate an alkene and water. Also known as dehydration since it involves the removal of a molecule of water.,Related Reactions : Dehydrohalogenation of Alkyl Halides Reaction of Alcohols with Hydrogen Ha

44、lides,伯、仲醇在铜或铜铬氧化物催化作用下脱氢形成羰基化合物 一般用于工业生产,Reaction usually proceeds via an E1 mechanism which proceeds via a carbocation intermediate, that can often undergo rearrangement. Primary alcohols will proceed via an E2 mechanism since the primary carbocation is highly unfavourable. Other common strong aci

45、ds such as HCl, HBr or HI are less suitable catalysts as nucleophilic substitution reactions will probably interfere.,Summery,Alcohol relative reactivity order : 3o 2o 1o Regioselectivity : Zaitsevs Rule. major product is usually the more highly substituted alkene (alkene stability) Zaitsevs Rule. S

46、tereoselectivity : trans- cis- again controlled by stability,Summary,15.14 Preparation of Ethers,Reaction type: Nucleophilic Substitution (SN2),Primary alcohols are converted to ethers on heating in the presence of an acid catalyst, usually sulfuric acid.,In general, this method is limited to the pr

47、eparation of symmetrical ethers in which both alkyl groups are primary.,Chenli,Mechanism For Of Alcohol Condensation To Give An Ether,Step 1: An acid/base reaction. Protonation of the alcoholic oxygen to make a better leaving group. This step is very fast and reversible. The lone pairs on the oxygen

48、 make it a Lewis base.,Step 2: The O of the second alcohol molecule functions as the nucleophile and attacks to displace the good leaving group, a neutral water molecule, by cleaving the C-O bond. This creates an oxonium ion intermediate.,Step 3: Another acid / base reaction. The proton is removed b

49、y a suitable base (here a water molecule, ROH is another alternative) to give the ether product.,Step 3,Step 2,Step 1,Reagents typically H2SO4 and heat. In general, typically limited to symmetrical ethers of primary alcohols. The method is not suitable for unsymmetrical ethers. The substitution invo

50、lves the O nucleophile of one alcohol attacking the electrophilic C in the other displacing a water molecule.,Summary,15.15 Oxidation of Alcohols,Reaction type: Oxidation-Reduction,Common reagents:,Primary alcohols,Primary alcohols can be oxidized to aldehydes (醛, 乙醛) or further to carboxylic(羧基的)ac

51、ids. In aqueous media, the carboxylic acid is usually the major product. PCC or PDC, which are used in dichloromethane, allow the oxidation to be stopped at the intermediate aldehyde.,Secondary alcohols,Secondary alcohols can be oxidized to ketone(酮)but no further:,Tertiary alcohols,Tertiary alcohol

52、s cannot be oxidised (no carbinol C-H),The outcome of oxidation reactions of alcohols depends on the substituents on the carbinol(甲醇, 原醇) carbon. In order for each oxidation step to occur, there must be H on the carbinol carbon,15.15.1 Cr Oxidation Of Alcohols,作为氧化剂的铬酸形式有： Na2Cr2O7 + 40 50% H2SO4 Cr

53、O3 + HAC CrO3吡啶络合物,Bp 97 ,Bp 49 50 %,直接蒸出,75 ,75 ,伯醇：先氧化得醛，醛易被氧化成羧酸,选择性氧化剂:可在室温下将醇氧化成醛(C5H5N)2CrO3PCCPDC,PCC: Pyridinium(吡啶(盐) chlorochromate,PCC,PDC: Pyridinium dichromate,15.15.2 Mn Oxidation of Alcohols,KMnO4: 醇在冷，稀，中性高锰酸钾下不被氧化 在较强烈条件下（如加热）下可氧化伯，仲醇,褐色,仲醇氧化成酮，并易被高锰酸钾进一步氧化使碳碳键断裂，故很少用于合成酮。 叔醇在中性，碱性下

54、不易被KMnO4氧化，在酸性条件下脱水成烯，尔后继续氧化，碳碳键断裂，生成小分子化合物,在碱性条件制得的，新制的MnO2可将碳上为不饱和键的伯，仲醇分别氧化为相应的醛酮，不饱和键不受影响。,不饱和键不受影响。,15.15.3 欧芬脑儿（Oppenauer,R.V）氧化法,Oppenauer 氧化法 在碱如三级丁醇铝或异丙醇铝的存在下，二级醇和丙酮（或甲乙酮、环己酮）一起反应（有时需加入苯或甲苯做溶剂），醇把两个氢原子转移给丙酮，醇变成酮，丙酮被还原成异丙醇。,异丙醇,异丙醇铝,可逆反应：可用于由酮制醇,反应特点,只有醇和酮之间发生氢原子的转移，不涉及分子的其它部分。 分子中含有碳碳双键或其它对

55、酸不稳定的基团时，利用此法较为适宜。因此该法也是由一个不饱和二级醇制备不饱和酮的有效方法,15.16 Diols,Nomenclature:,Diols are named systematically as poly-alcohols: e.g. HOCH2CH2OH = 1,2-ethanediol, (ethylene glycol 乙二醇)so the same nomenclature rules as for alcohols apply. 1,2-diols are often referred to as vicinal diols. Functional group suffix = -diol Functional group prefix = dihydroxy-,cis-