Orgo, Chapter 12: Alcohols from Carbonyl Compounds

12.5 Organometallic Compounds

- compounds that contain carbon-metal bonds - the reactivity of organometallic compounds increases with the percent ionic character of the carbon-metal bond - they react explosively with water and burst into flame when exposed to air

12.4F Spectroscopic Evidence for Alcohols

- give rise to broad O-H stretching absorptions from 3200 to 3600 in IR - alcohol hydroxyl hydrogen produces a broad 1H NMR signal - 1H NMR between 3.3 and 4.0 - 13C NMR spectrum of an alcohol between 50 and 90

12.7B Reactions of Grignard Reagents with Epoxides

- grignard reagents act as nucleophiles with epoxides, providing convenient synthesis of alcohols - the alkyl group of the grignard reagent attacks the partially positive carbon of the epoxide ring - the ring opens, add H3O+ and alcohol forms - grignard reagents react primarily at the less substituted ring carbon atom of a substituted epoxide

12.6 Prep of Organolithium and Organomagnesium Compounds: 12.6A Organolithium Compounds

- often prepared by the reduction of organic halides with lithium metal, carried out in ther solvents R-X + 2Li --Et2O--> RLi + LiX

12.3CSummary of LiAlH4 and NaBH4 Reactivity

- order of reactivity: acids<esters<ketones<aldehydes

12.4D Pyridinium Chlorochromate (PCC)

- under conditions that exclude water - 1 alcohols to aldehydes

12.4E Potassium Permanganate (KMnO4)

- 1 alcohols to aldehydes and then carboxylic acids - 2 alcohols to ketones

12.3 Alcohols by Reduction of Carbonyl Compounds

- 1 and 2 alcohols can be synthesized by reduction of variety of compounds that contain the carbonyl group

12.8C The Use of Lithium Reagents

- Orgolithium reagents react with carbonyl comp in the same way as G reagents, providing an alternative method - they are somewhat more reactive, but more difficult to handle and prepare

12.2 Oxidation-Reduction Reactions: reduction

- Reduction of an organic molecule usually corresponds to the increase in hydrogen content or to decrease in oxygen content - Ex: converting a carboxylic acid to an aldehyde b/c oxygen content is decreasing - use the symbol: [H] to indicate reduction

12.3B Sodium Borohydride

- aldehydes and ketones are easily reduced by NaBH4 - preferred over LAH for aldehydes and ketones as it can be safely and effectively used in water and alcohol solvents usually MeOH

12.8D The Use of Sodium Alkynides

- also react with aldehydes and ketones to yield alcohols - page 559

12.1 Structure of the Carbonyl Group

- can be an aldehyde, ketone, carboxylic acid, ester or amide - sp2 hybridized, triginal planar, 120 degrees - more electronegative oxygen strongly attracts the electrons of sigma and pi, causing the carbonyl group to be highly polarized - carbon atom bears a substantial positive charge and the oxygen atom bears a substantial negative charge-- seen with large dipole moment

12.9 Protecting Groups

- can be used in some cases where a reactant contains a group that is incompatible with the reaction conditions necessary for a given transformation - protecting groups: TBS, Imidazole, DMF

12.7A Reactions with Compounds Containing Acidic Hydrogen Atoms

- grignard and organolithium comp are very strong bases that react with any compound taht has a hydrogen atom attached to an electroneg atom like O, N or S - page 550

12.8B Restrictions on the Use of Grignard Reagents

- grignard reagent is a very powerful base - it is not possible to prepare a grignard reagent from a compound that contains any hydrogen more acidic than the hydrogen atoms of an alkane or alkene - cannot prepare G reagent from an organic compounds containing several groups as it would react and the formation of the G reagent would fail - when we prepare G reagents we are limited to alkyl halides or to analogous orgo halides containing C-C double bonds, internal triple bonds, ether linkages and -NR2 groups

12.4C Chromic Acid (H2CrO4) Oxidation

- involve formation of chromate esters and include an elimination step - Jones reagent (H2CrO4) used as oxidizing species - can be prepared by adding CrO3 or Na2CrO4 to aqueous sulfuric acid -used for breathalyzer alcohol test - page 545

12.7C Reactions of Grignard Reagents with Carbonyl Compounds

- most important synthetic rxns of grignard reagents and orgolith comp are those in which they react as Nu-'s and attack an unsat carbon - page 552

12.1A Reactions of Carbonyl Compounds with Nucleophies

- nucleophilic addition to the carbonyl group is common as there is a partial positive charge on the carbon - when Nu- adds to the carbony lgroyp, it uses an electron pain=r to form a bond to the carbron attom - an election pair from the C-O double bond shifts to the oxygen with a negative charge - goes from trigonal planar sp2 to tetrahedral sp3 -two important Nu-'s that add: hydride ions (NaBH4 or LiAlH4) and carbanions (RLi or RMgX) - oxidation or reduction may also take place

12.2 Oxidation-Reduction Reactions: oxidation

- oxidation corresponds to increasing the oxygen content and decreasing the hydrogen content - use the symbol: [O] - technically, oxidation is a reaction that increases a compounds content of any element more electronegative than carbon

12.6B Grignard Reagents (Organomagnesium halides)

- prepared by the reaction of an organic halide with magnesium metal in an anhydrous ether solvent - prepared better with RI and RBr

12.4 Oxidation of Alcohols

- primary alcohols can be oxidized into aldehydes, aldehydes can be oxidized into carboxylic acids - secondary alcohols can be [O] to ketones - tertiary alcohols CANNOT be oxidized to carbonyl compounds -in all of them when [O] takes place, a hydrogen atom is lost from the alcohol or aldehyde carbon

12.3D Reduction of Alkyl Halides to Hydrocarbons: RX-->RH

- use 1) LiAlH4, Et2O; 2)H2O/H2SO4 - replace H with D in LiAlH4 if want to replace halogen atom with deuterium

12.4B Swern Oxidation

- useful for the synthesis of aldehydes and ketones from 1 and 2 alcs - rxn conducted in absence of water so that 1 alcs that form aldehydes do not continue and form carboxylic acids - 2 alcs form ketones - page 543

12.3A Lithium Aluminum Hydride (LiAlH4)

-LiAlH4 reduces carboxylic acids and esters to primary alcohols - yields two alcohols - carboxylic acids and esters are more difficult to reduce that aldehydes and ketones -LiAlH4 is a strong enough reducting agent to reduce them -mst avoid the presence of water or any other weakly acidic solvent like alcohols as it reacts violently with proton donors to release hydrogen gas - Et2O and THF are commonly used solvents for LAH reductions

12.4A A Common Mechanistic Theme

-[O] of 1 and 2 alcs follow mechanistic path when certain reagents used - the reagents temporarily install a leaving group on hydroxyl oxygen during the rxn - loss of H from the hydroxyl carbon and departure of LG from O result in elimination that forms C double bond O pi bond - page 542 and 543

12.8 Alcohols from Grignard Reagents

1) Grig Reagents react with formaldehyde to give a primary Alcohol 2)Grignard Reagents React with all other aldehydes to give secondary alcs 3)Grig reagents react with ketones to give 3 alcs 4)Esters react with two molar equivalents of a grignard reagent to form 3 alcs