Reactions of Alcohols PDF

1,2,5,7,8,9,11,14 Dr. Derar AL-smadi 2 11-1 Oxidation States of Alcohols and Related Functional Groups In inorganic chemistry, we think of oxidation as a loss of electrons and reduction as a gain of electrons. This picture works well for inorganic ions, as when Cr6+ is reduced to Cr3+. Most organ...

1,2,5,7,8,9,11,14 Dr. Derar AL-smadi 2 11-1 Oxidation States of Alcohols and Related Functional Groups In inorganic chemistry, we think of oxidation as a loss of electrons and reduction as a gain of electrons. This picture works well for inorganic ions, as when Cr6+ is reduced to Cr3+. Most organic compounds are uncharged, however, and gain or loss of electrons is not obvious. We can tell that an oxidation or a reduction of an alcohol has taken place by counting the number of C¬O bonds to the carbon atom. Oxidation usually converts C¬H bonds to C¬O bonds. 3 4  11-2 Oxidation of Alcohols A wide variety of oxidants are used: Chromium oxides (Cr2O7-2), permanganate (MnO4-) ,nitric acid (HNO3), and sodium hypochlorite (NaOCl, household bleach) All of the common oxidants have an element (Cr, Cl, I, S, Mn, or others) in a high oxidation state bonded to oxygen 11-2A Oxidation of Secondary Alcohols 2° alcohol becomes a ketone. 5  11-2 Oxidation of Alcohols Oxidizing agent is Na2Cr2O7/H2SO4. Active reagent probably is H2CrO4. Color change is orange to greenish-blue 6  11-2 Oxidation of Alcohols 11-2B Oxidation of Primary Alcohols primary alcohols oxidizes to carboxylic acids. The oxidizing agent is too strong to stop at the aldehyde 7 11-2 Oxidation of Alcohols PCC is a complex of chromium trioxide, pyridine, and HCl. Oxidizes primary alcohols to aldehydes. Oxidizes secondary alcohols to ketones 8  11-2 Oxidation of Alcohols 11-2C Resistance of Tertiary Alcohols to Oxidation Carbon does not have hydrogen, so oxidation is difficult and involves the breakage of a C—C bond. Chromic acid test is for primary and secondary alcohols because tertiary alcohols do not react 9 10 11  11-5 Alcohols as Nucleophiles and Electrophiles; Formation of Tosylates Alcohol as a Nucleophile ROH is a weak nucleophile. New O—C bond forms; O—H bond breaks RO- is a strong nucleophile. 12  11-5 Alcohols as Nucleophiles and Electrophiles; Formation of Tosylates Alcohol as an Electrophile OH- is not a good leaving group. Protonation of the hydroxyl group converts it into a good leaving group (H2O). 13  11-5 Alcohols as Nucleophiles and Electrophiles; Formation of Tosylates Alcohols can be converted to a tosylate ester. The tosylate group is an excellent leaving group and it also convert an alcohol to an electrophile 14  11-5 Alcohols as Nucleophiles and Electrophiles; Formation of Tosylates SN2 Reactions with Tosylates The SN2 mechanism (strong nucleophile) is more commonly used in synthetic preparations than the SN1 The reaction shows the SN2 displacement of the tosylate ion (-OTs) from (S)-2-butyl tosylate with inversion of configuration. The tosylate ion is a particularly stable anion, with its negative charge delocalized over three oxygen atoms 15 16 11-5 Alcohols as Nucleophiles and Electrophiles; Formation of Tosylates 17  11-7 Reactions of Alcohols with Hydrohalic Acids In acidic solution, the hydroxyl group is protonated by an acid to convert it into a good leaving group (H2O). Once the alcohol is protonated a substitution or elimination reaction can take place, depending on the structure (1°, 2°, 3°) of the alcohol It converts alcohols to alkyl halides 18  11-7 Reactions of Alcohols with Hydrohalic Acids Reaction with HBr 3° and 2° alcohols react with Br- via SN1. 1° alcohols react via SN2 19 20 11-7 Reactions of Alcohols with Hydrohalic Acids 21  11-7 Reactions of Alcohols with Hydrohalic Acids Reaction with HCl Chloride is a weaker nucleophile than bromide. Add ZnCl2, which bonds strongly with –OH, to promote the reaction. The chloride product is insoluble. Lucas test: ZnCl2 in concentrated HCl: 1° alcohols react slowly or not at all. 2 ° alcohols react in 1-5 minutes. 3 ° alcohols react in less than 1 minute 22  11-7 Reactions of Alcohols with Hydrohalic Acids Secondary and tertiary alcohols react with the Lucas reagent (HCl and ZnCl2) by the SN1 mechanism 23  11-7 Reactions of Alcohols with Hydrohalic Acids Primary alcohols react with the Lucas reagent (HCl and ZnCl2) by the SN2 mechanism. Reaction is very slow. The reaction can take from several minutes to several days ` 24  11-7 Reactions of Alcohols with Hydrohalic Acids 11-7C Limitations on the Use of Hydrohalic Acids with Alcohols 25 26  11-8 Reactions of Alcohols with Phosphorus Halides Several phosphorus halides are useful for converting alcohols to alkyl halides not stable Good yields with 1° and 2° alcohols, but none works well with tertiary alcohols PCl3 or PCl5 for alkyl chlorides (but SOCl2 is better). PBr3 for alkyl bromides. P and I2 for alkyl iodides (PI3 not stable). 27 11-8 Reactions of Alcohols with Phosphorus Halides 28 11-8 Reactions of Alcohols with Phosphorus Halides. The final step is an SN2 displacement where bromide attacks the back side of the alkyl group. This attack is hindered if the alkyl group is tertiary. 29 11-8 Reactions of Alcohols with Phosphorus Halides 30  11-9 Reactions of Alcohols with Thionyl Chloride Thionyl chloride (SOCl2) can be used to convert alcohols (1° and 2° ) into the corresponding alkyl chloride in a simple reaction that produces gaseous HCl and SO2. 31  11-9 Reactions of Alcohols with Thionyl Chloride This mechanism resembles the SN1, except that the nucleophile is delivered to the carbocation by the leaving group, usually giving retention of configuration as shown in the following example. (Under different conditions, retention of configuration might not be observed.) 32 11-9 Reactions of Alcohols with Thionyl Chloride 33  11-11 Unique Reactions of Diols Vicinal diols can undergo the following two reactions: Pinacol rearrangement Periodic acid cleavage 11-11A The Pinacol Rearrangement The pinacol rearrangement is formally a dehydration and produces Ketone The reaction is acid-catalyzed 34 11-11 Unique Reactions of Diols 35 11-11 Unique Reactions of Diols 36  11-11 Unique Reactions of Diols 11-11B Periodic Acid Cleavage of Glycols 1,2-Diols (glycols) is formed by dihydroxylation of alkenes by osmium tetroxide or cold potassium permanganate , and the cleavage of the glycol by periodic acid (HIO 4) Periodic acid cleavage of 1,2-diols is commonly used to determine the structures of unknown sugars, because it only cleaves a bond between two carbon atoms if there is a free ¬OH group on each carbon 37 11-11 Unique Reactions of Diols 38  11-14 Reactions of Alkoxides Ethers can be synthesized by the reaction of alkoxide ions with primary alkyl halides in what is known as the Williamson ether synthesis. This is an SN2 displacement reaction works better with primary alkyl halides to facilitate back-side attack. If a secondary or tertiary alkyl halide is used, the alkoxide will act as a base and an elimination will take place 39  11-14 Reactions of Alkoxides In proposing a Williamson synthesis, we usually choose the less hindered alkyl group to be the halide (or tosylate) and the more hindered group to be the alkoxide ion. 40 11-14 Reactions of Alkoxides 41 42 43 44 45 46 47