CHEM 203 Topics Discussed on Nov. 25 Toxic and carcinogenic properties of Cr(VI) compounds – including CrO3 Electrophilic reactivity of metal-oxo linkages, Mt=O: Nu: O O O nucleophiles add Mt Nu Mt = any metal Mt Mt easily to the metal Pyridinium chlorochromate (PCC): electrophilic O metal-oxo O Cl Cr O linkage N N Cr Cl H O O VI O H chromium trioxide: a pyridinium pyridinium chlorochromate common source of Cr (VI) chloride PCC oxidation of primary alcohols to aldehydes & secondary alcohols to ketones R CH OH VI O O 2 O VI O H O generic α Cr ± H+ H Cr a special type primary Cl Cr O O α VI C O OH alcohol O R H C O of elim. react. H R H substitution of chloride a chromate ester IV OH complex R O + O Cr Cr(III) + Cr(VI) OH redox rxs. H an aldehyde a Cr(IV) complex fine details of the mechanism of PCC oxidation remain unclear. The mechanism shown above is one of a number of plausible mechanism that differ for the precise sequence of events leading to the Cr(VI) complex that ultimately decomposes to give the carbonyl product. OH PCC O Likewise: R1 R1 2 2 H R R a ketone generic secondary alcohol The conversion of an alcohol into a carbonyl compound as an oxidation reaction Lecture of Nov. 25 p. 2 oxid. st. = –1 if R2 = H overall: oxid. st. = +1 if R2 = H oxid. st. = 0 if R2 = alkyl oxid. st. = +2 if R2 = alkyl H R1 O O O 1 + Cr R C OH + Cl Cr O 2 C VI R O IV OH R2 O Cl the OH-bearing C atom advances from the oxidation state of –1 or 0 to that of +1 or +2: it undergoes a two-electron oxidation. the Cr atom recedes from the oxidation state of +6 to that of +4: it undergoes a two-electron reduction. Inability of tertiary alcohols to undergo oxidation, due to the absence of α-H's Conversion of chromium trioxide into chromic acid, H2CrO4 (the Cr analog of H2SO4) electrophilic O O H ± H+ O H2O chromic acid: a metal-oxo Cr O Cr O HO Cr OH VI Cr(VI) compound linkage O VI O VI H O O The Jones reagent: a solution of chromic acid, H2CrO4, in aqueous H2SO4: O O H + O the Jones reagent is electrophilic H2O ± H metal-oxo Cr O Cr O HO Cr OH prepared by adding VI VI linkage O VI O O H O CrO3 to aq. H2SO4 chromic acid: a Cr(VI) compound IMPORTANT: PCC is used ONLY in anhydrous (=water-free) media, while Jones rgt. is an aqueous solution. This seemingly minor difference has a major influence on the course of the reaction of primary alcohols with the two reagents. The Jones reagent: oxidation of primary alcohols to carboxylic acids and secondary alcohols to ketones in aqueous medium Reaction of the Jones reagent with primary alcohols: initial formation of a chromate ester: OH OH O O VI O VI H Cr OH ± H+ H Cr OH HO Cr OH α α VI O OH R CH2 OH C O C O O R H R H H Reaction of the Jones reagent with primary alcohols: decomposition of the chromate ester to give an aldehyde: Lecture of Nov. 25 p. 3 VI OH R O O OH Hα Cr OH H R C O H an aldehyde but the aldehyde is not the final product of the reaction (the carboxylic acid is): evidently, something must happen to the aldehyde that causes it to become a carboxylic acid… Acid-promoted equilibration of the aldehyde with a geminal diol in aqueous acid: H H H H O O H H R O H R O O OH H H OH H O R R OH + H O H H very H H H H electrophilic a geminal ("gem") diol note: geminal diols (obtained by the reversible hydration of carbonyl functions) display a pair of OH groups connected to the same carbon atom. Vicinal diols (obtained by OsO4 oxidation of alkenes) have their OH groups connected to adjacent carbon atoms: OH HO OH R1 C OH R1 C C R4 R2 R2 R3 a geminal diol: both OH groups a vicinal diol: the OH groups are are attached to the same C atom attached to adjacent C atoms (iii) further oxidation of the gem-diol to an acid by Cr(VI) through a second round of the mechanism shown earlier: H2CrO4 OH "round II" O R CH OH R C OH [ + Cr(III) ] gem-diol of Jones carboxylic acid mechanism Oxidation of secondary alcohols to ketones with the Jones reagent; e.g.: HO OH O HO O R2 Cr ± H+ Cr OH R1 O a generic HO Cr OH OH O secondary R1 C OH H O O 1 O 2 alcohol O R1 C R C R H H 2 H R2 a ketone R + note: ketones can — and do — form geminal diols by reaction with H3O , but the geminal diol of a ketone cannot undergo further oxidation because it has no α-H's Lecture of Nov. 25 p. 4 Summary of the above oxidation reactions: R–CH2–OH to R–CHO possible only in a water-free medium: requires PCC R–CH2–OH to R–COOH possible only in an aqueous medium: requires Jones reagent R1R2CH–OH to R1R2C=O may be achieved with either PCC or Jones reagent Principle: any carbonyl compound will equilibrate with the corresponding geminal (gem-) diol in an aqueous acidic medium. However, gem-diols are thermodynamically disfavored relative to carbonyls, and this primarily on entropic grounds. Therefore, any attempt to isolate gem-diols will actually return the corresponding carbonyl compounds (at least as far as the carbonyl compounds seen in CHEM 203 are concerned) H H H H O O H H R1 O H R1 O O OH H O H OH 1 a geminal R1 R OH ("gem") diol 2 2 2 R H R 2 R R Overall ΔG slightly positive .