(Neither an oxidation or reduction: Addition or loss of H +, H 2 O, HX).

Transcription

1 eactions of Alcohols Alcohols are versatile organic compounds since they undergo a wide variety of transformations the majority of which are either oxidation or reduction type reactions. xidation is a loss of electrons eduction is a gain of electrons. But in organic terms: xidation: loss of 2 ; addition of or 2 ; addition of X 2 (halogens). eduction: addition of 2 or - ; loss of or 2 ; loss of X 2. (Neither an oxidation or reduction: Addition or loss of, 2, X). xidation-eduction Chart: xidation alkane primary alcohol aldehyde acid secondary alcohol ketone tertiary alcohol eduction Ch11 eacns of Alcohols.doc Page1

2 xidation of Alcohols Primary and secondary alcohols are easily oxidized by a variety of reagents. econdary Alcohols The most common reagent used for oxidation of secondary alcohols to ketones is chromic acid, 2 Cr 4. secondary alcohol Na 2 Cr 2 7, 2 4 ketone Chromic acid is produced in situ by reaction of sodium dichromate, sulfuric acid and water. Na 2 Cr Cr 4 2 Na 4 Mechanism of oxidation Cr Cr 2 chromic acid (CrVI) chromate ester Cr Cr - (CrIV) 3 2 : The alcohol and chromic acid produce a chromate ester, which then reductively eliminates the Cr species. The Cr is reduced (VI IV), the alcohol is oxidized. Ch11 eacns of Alcohols.doc Page2

3 xidation of Primary Alcohols Primary alcohols are easily oxidized just like secondary alcohols, but the product of oxidation is an aldehyde. primary alcohol [] aldehyde [] acid owever, the aldehyde can also be easily oxidized to an acid, and this overoxidation is a practical problem. E.g. C 2 Na 2 Cr 2 7, 2 4 C 2 A common reagent that selectively oxidizes a primary alcohol to an aldehyde (and no further) is pyridinium chlorochromate, PCC. N: Cr 3, (PCC) E.g. PCC aldehyde Ch11 eacns of Alcohols.doc Page3

4 Tertiary Alcohols These are resistant to oxidation because they have no hydrogen atoms attached to the oxygen bearing carbon (carbinol carbon). ther xidizing eagents Potassium permanganate is a cheaper but stronger oxidizing agent, and conditions must be controlled carefully. KMn 4, base Thermal dehydrogenation is the cheapest method of oxidation but the high temperatures involved limit the applicability of this method. Cu, 300 o C eduction of Alcohols Normally an alcohol cannot be directly reduced to an alkane in one step. LiAl 4 X The group is a poor leaving group so hydride displacement is not a good option however the hydroxyl group is easily converted into other groups that are superior leaving groups, and allow reactions to proceed. ne such conversion involves tosyl chloride, and the formation of a tosylate. Ch11 eacns of Alcohols.doc Page4

5 Ts-, py C 3 LiAl 4 Ts or Tosylcyclohexyl tosylate Cyclohexanol will not reduce with LiAl 4, but the corresponding tosylate reduces to cyclohexane very easily. Tosylate Esters These compounds undergo substitution and elimination very easily (often more reactive than alkyl halides). N - N - - Ts- C 3 C 3 Tosylate Ester -Ts Tosylate esters (tosylates) are typically formed from alcohols with reaction with Ts- and pyridine (py). I: - C 3 C 2 3 C -Ts N 2 I C 2 C 3 C 3 - Ts () () Tosylate groups undergo a variety of 2 reactions. N The tosylate is such a good leaving group because it is a stable anion. Ch11 eacns of Alcohols.doc Page5

6 Ts = C 3 C 3 C 3 Common N 2 transformations of Tosylates: Ts C N -CN Br - -Br ' - -' :N 3 -N 2 LiAl 4 - Alcohols and ydrohaloic Acids Alkyl halides can also be formed by reaction of alcohols with -X acids. - -Br -Br 2 In acidic media, the alcohol is in equilibrium with its protonated form. - Br - N 1 or 2 N Br 2 The is a poor leaving group, but 2 is an excellent leaving group, and once the - is protonated the molecule may take place in a variety of substitution and/or elimination reactions. Ch11 eacns of Alcohols.doc Page6

7 The nature of determines whether the reactions proceed via N 1 or N 2 mechanisms. (If is primary alkyl N 2 If is bulky tertiary alkyl N 1). ydrochloric Acid - reacts in the same way, although often Zinc (II) chloride (a Lewis acid) is added to help compensate for the lower nucleophilicity of chloride ion. The mixture of and Zn 2 is called the Lucas eagent. econdary and tertiary alcohols react via the N 1 mechanism with the Lucas reagent. C 3 Zn C _ 3 2 Zn C C C 3 C 3 C C 3 3 The Zn 2 coordinates to the hydroxyl oxygen, and this generates a far superior leaving group. C 3 Zn 2 - _ Zn 2 C 3 Zn 2 C 3 C 3 Primary alcohols react in a similar fashion except the free cation is not generated, and the substitution is of N 2 type. Limitations of use of -X 1) nly works for - and -Br 2) Low chemical yields for primary and secondary alcohols 3) ften observe competing elimination 4) Carbocations can lead to rearranged products Ch11 eacns of Alcohols.doc Page7

8 Phosphorous alides Phosphorous halides can convert alcohols to alkyl halides. E.g. 3 - P P() PBr 3 3 -Br P() 3 - P 5 - P 3 PI 3 has to be generated in situ via reaction of iodine and phosphorous. E.g. C 3 (C 2 ) 14 C 2 - P/I 2 C 3 (C 2 ) 14 C 2 -I This type of reaction does not work well for tertiary alcohols, and also does not lead to rearranged products. These observations are explained by the reaction mechanism. Mechanism The hydroxyl oxygen displaces a halide (good leaving group) from the Phosphorous. Br P Br Br Br - Br P Br Br The liberated halide performs an N 2 type attack on the back side of the group. The positively charged oxygen is a good leaving group. Thionyl Chloride Thionyl chloride ( 2 ) is the usual method of choice for preparing alkyl chlorides from alcohols. 2 Ch11 eacns of Alcohols.doc Page8

9 The mechanism is interesting: The hydroxyl oxygen attacks the electrophilic ulfur, and from the tetrahedral intermediate a chloride is ejected The chlorosulfite ester rearranges with the breaking of the C- and - bonds and the formation of the - bond and a new - bond. When is secondary or tertiary, the ionization to a cation probably precedes the Chloride attack, whereas if is primary the process is probably concerted (Bond breaking and forming at the same time). ummary of Best Alcohol to Alkyl alide Transformations ass Chloride Bromide Iodide Primary 2 PBr 3 P/I 2 econdary 2 PBr 3 P/I 2 Tertiary Br I Dehydration eactions of Alcohols Dehydration of alcohols requires an acidic catalyst to convert the hydroxyl into a good leaving group this is an equilibrium reaction. 2 Ch11 eacns of Alcohols.doc Page9

10 It is possible to force the equilibrium to the right (alkene) by removing one or both of the products. This is normally achieved either by distillation (alkene is lower boiling than alkyl halide) or the addition of a dehydrating agent. Alcohol dehydration usually occurs via the E1 mechanism. 2 2 : The first step is the exothermic protonation of the hydroxyl, followed by the slow, endothermic, rate determining ionization to generate the cation. The fast deprotonation is exothermic and produces the alkene. Figure 11-2 ince the D is the formation of the carbocation, the ease of formation dictates the reaction rates of 3 > 2 > 1. earrangements are common since a free carbocation is involved. Ch11 eacns of Alcohols.doc Page10

11 E.g. C 3 C 2 C 2 C 2 - C 3 C=CC 3 C 2 =CC 2 C 3 2 a - a b - b C 3 3 C major product disubstituted alkene C 2 C 2 C 3 minor product mono substituted alkene After 1-butanol is protonated, the ionization is accompanied by a hydride shift to produce a secondary carbocation. There is a choice of protons to be eliminated, and aytzeff s rule applies. Bimolecular Dehydration to form Ethers In certain cases, a protonated primary alcohol may be attacked by another molecule of alcohol. The net result is a dehydration and a formation of an ether. E.g. C 3 C 2 3 C C 3 C 2 C 3 - C 3 C 2 C 2 C 3 Bimolecular dehydration is best used for the synthesis of symmetrical dialkyl ethers from unhindered primary alcohols. Ch11 eacns of Alcohols.doc Page11

12 Unique eactions of Diols (Pinacol earrangement) C 3 C C C 3 3 C C 3 C 3 C 3 2 pinacol pinacolone The pinacol rearrangement is a formal dehydration. Mechanism C 3 C 3 C 3 C 3 3 C C 3 3 C C 3 2 C 3 3 C C 3 C 3 C 3 C 3 3 C C 3 methyl shift C 3 3 C C 3 2 : C 3 C 3 3 C C 3 C 3 The protonation of the hydroxyl is followed by ionization. The tertiary carbocation rearranges with a methyl shift to produce a tertiary cation which has the extra benefit of resonance stabilization. The rearranged product is deprotonated to generate the final product. Ch11 eacns of Alcohols.doc Page12

13 eavage of Glycols Periodic acid will cleave 1,2 diols to give aldehyde and ketone products. s 4 I syn diol (The treatment of an alkene to syn hydroxylation followed by periodic acid cleavage is an alternative to the ozonolysis-reduction procedure described earlier). Mechanism I4 I = The mechanism involves the formation of a cyclic periodate ester, which cleaves to generate to carbonyl groups. Esterification of Alcohols Usually the term ester means the ester of a carboxylic acid. In general, an acid and alcohol generate an ester and water. This is called a Fischer esterification. ' C C ' 2 alcohol acid ester Ch11 eacns of Alcohols.doc Page13

14 Acid chlorides provide another route to producing esters. ' C C ' alcohol acid chloride ester Esters of Inorganic Acids Just as alcohols form esters with carboxylic acids, they also form esters with inorganic acids. C 3 C 3 p-toluenesulfonic acid Ts 2 p-toluenesulfonate ester Ts sulfuric acid methylsulfate (sulfate ester) N - N - nitric acid alkyl nitrate ester 2 2 Phosphate esters are important in nature since they link the nucleotide bases together in DNA. P P 2 phosphoric acid methylphosphate (phosphate ester) Ch11 eacns of Alcohols.doc Page14

15 eactions of Alkoxides Alkoxide ions are produced when metals like Na or K are added to alcohols. - Na - Na ½ 2 The sodium (or potassium) alkoxides are strong bases and nucleophiles. Alkoxides can react with primary alkyl halides (or tosylates) to produce ethers. This is the Williamson Ether synthesis, and it involves N 2 displacement with back side attack of the alkoxide. C 3 C 2 : - 3 C I Na C 3 C 2 -C 3 NaI ether Normally this reaction is limited to unhindered primary alkyl halides, otherwise elimination tends to be the preferred mode of reaction. Ch11 eacns of Alcohols.doc Page15