380 likes | 392 Views
Learn about alcohol reactions such as E1, E2, E1cB, and synthesis methods like Williamson Ether Synthesis. Understand oxidation, cleavage reactions, and quinone formation. Discover how phenols lead to quinones and explore the synthesis pathways from 2-phenylethanol. Practice predicting products and proposing reagents.
E N D
CH21 –AY 2013-2014 SEM II -- R.D. A. Bolinas 8.4 Reactions of Alcohols
Alcohols can undergo E1/E1cB/E2 reactions to form alkenes • By protonating –OH in acid, we get an oxonium –OH2+ that can leave as H2O • E1/E2 depends on the nature of ROH, but usually E1 prevails, except for 1° alcohols (E2)
Alcohols can undergo E1/E1cB/E2 reactions to form alkenes • Predict the major product. Remember Zaitsev’s rule!
Alcohols can undergo E1/E1cB/E2 reactions to form alkenes • Predict the major product. Remember Zaitsev’s rule!
Alcohols can undergo E1/E1cB/E2 reactions to form alkenes • E1cB occurs in biological systems: • the -OH group is two carbons away from a carbonyl (C=O) group
Alcohols can be oxidized into carbonyls… • We use oxidizing agents: • periodinane(with Iodine in +5 oxidation state) • PRIMARY R-OH TO ALDEHYDE ONLY
Alcohols can be oxidized into carbonyls… • We use oxidizing agents: • Acidic CrO3/CrO42- (with Chromium in +6 oxidation state) • PRIMARY R-OH TO CARBOXYLIC ACID
Alcohols can be oxidized into carbonyls… • Secondary alcohols will give ketones with either reagent
Alcohols can be oxidized into carbonyls… Periodinane
The Williamson Ether synthesis uses an alkoxide and alkyl halide… • Ethers (R-O-R) • SN2 reaction between R-X and R-O-
The Williamson Ether synthesis uses an alkoxide and alkyl halide… • SN2 reaction between R-X and R-O- • WE NEED TO CONSIDER STERIC HINDERANCE. This might lead to E2! Backside attack is not favorable! Methoxide is also a very strong base.
The Williamson Ether synthesis uses an alkoxide and alkyl halide… • Practice:
The Williamson Ether synthesis uses an alkoxide and alkyl halide… • Practice:
Phenols can sometimes react like alcohols in forming ethers. • CANNOT: be dehydrated with acid, convert into halides with HX • CAN: convert to ether via Williamson ether synthesis, react via EArS (review) The aromatic ring allows the H+ to leave easily, making phenols ACIDIC.
Oxidation of phenols gives us QUINONES • Because they don’t have a hydrogen on the C-OH carbon, phenols become quinones
Oxidation of phenols gives us QUINONES • Quinones easily change form into hydroquinones
Ethers generally undergo only acidic cleavages. • Ethers are unreactive to most common reagents • Only strong acids can usually react with them: HI/HBr via SN1 or SN2
Ethers generally undergo only acidic cleavages. • Ethers are unreactive to most common reagents • Only strong acids can usually react with them: HI/HBr via SN1 or SN2 SN1
Cyclic ethers are also generally as unreactive, except for EPOXIDES. • Epoxides come from alkenes + peroxy acids • High angular strain induces reactivity. • SN2 attacks with H3O+ or HX lead to trans-diolor trans-halohydrins, other nucleophiles work too.
Cyclic ethers are also generally as unreactive, except for EPOXIDES. • SN2 attacks with H3O+ or HX lead to trans-diolor trans-halohydrins, other nucleophiles work too. beta-blocker that is used for treatment of cardiac arrhythmias, hypertension, and heart attacks
Sulfur analogs of alcohols and ethers are called thiols and sulfides.
Thiols can be made via SH- and RX, and can react via Williamson mechanism SN2 Synthesis: Williamson thioether synthesis
Disulfides are formed via oxidation. Reduction to thiols can occur as well. http://delight.spslinfotechpvtl.netdna-cdn.com/media/catalog/product/cache/1/image/650x650/9df78eab33525d08d6e5fb8d27136e95/r/e/rebonding.jpg http://b.vimeocdn.com/ts/147/230/147230470_640.jpg
Disulfides are formed via oxidation. Reduction to thiols can occur as well. For rebonding: Thioglycolate (acid-like) to convert disulfide bonds in hair protein to thiolates Hydrogen peroxide to oxidize the thiolates back to disulfides. Reforming the disulfides helps re-align amino acids and make hair straight http://delight.spslinfotechpvtl.netdna-cdn.com/media/catalog/product/cache/1/image/650x650/9df78eab33525d08d6e5fb8d27136e95/r/e/rebonding.jpg
Disulfides are formed via oxidation. Reduction to thiols can occur as well. “antioxidant” because it protects your cells from oxidative degradation. http://b.vimeocdn.com/ts/147/230/147230470_640.jpg
Propose a synthetic route from 2-phenylethanol to make: E A D B C
Propose a synthetic route from 2-phenylethanol to make: 1. H2SO4 2. H2/Pd H2SO4 KMnO4 Periodinane CrO3
More synthetic routes: propose reagents for each step! Convert to Grignard (Mg/ether) add CH2=O then acid PBr3 NaBH4, H3O+ Periodinane Ph-CH2-MgBr 2. H3O+ conc’dH2SO4