alcohol oxidation and reduccion

Copyright, Arizona State University Oxidation and Reduction (more ) Alcohols Nomenclature Notation, recall H H C OH R H R 1o, primary C R' R' R'' C OH R 3o, tertiary OH 2o, secondary • IUPAC naming priority, alcohol > alkene ~ alkyne > halide (more oxidized functional groups have higher priority) • suffix: -ol CH3 OH CH3 CH2 OH 1-ethnol ethan-1-ol (ethanol) methanol HO OH phenol 1 sterochemistry ignored HO (2S,5)-dimethylhept-(4E)-en-1-ol 6-methyl-3-propyl-2-heptanol • note the use of number directly before the functional group in the example on the right, used when we have multiple functional groups Some Common Alcohols with Common Names: (I won't test you on these!) OH HO OH OH HO OH ethylene glycol iso-propanol OH glycerol benzyl alcohol Alcohol Acidity, Return to Substituent Effects (more ) • Alcohols are weak acids, the -OH bonds are similar to those in water Example: Simplest alcohol methanol pKa ~15.5 ~15.5 H2O H2O H2O CH3OH HO hydroxide CH3O methoxide conjugate base anion + H3 O+ + H3 O+ • the conjugate base anion of water is the hydroxide anion • the conjugate base anion of an alcohol is the alkoxide anion, i.e the conjugate base anion of ethanol is the ethoxide anion Simple Resonance effects significantly influence alcohol Bronsted acidity Alcohols Copyright, Arizona State University pKa H 2O OH ~19.0 + H 3O + O cyclohexanol H2O OH ~9.0 O O O O phenol • the energy of the non-bonding electrons in the conjugate base anion of phenol are lower compared to cyclohexanol due to resonance delocalization/stabilization, phenol is the stronger acid, has the smaller pKa 2.1 Substituent Effects: Important General Concept • There are TWO main kinds of substituent effects, INDUCTIVE effect substituents and RESONANCE effect substituents • Simple Alkyl substituents can be considered to be a special from of resonance effect substituents, they operate by HYPERCONUUGATION • In the context of alcohol acidity we also need to consider solvent effects X Recall the Inductive Substituent Effect: Withdrawal of electrons through sigma-bonds due to electronegativity pKa F NO resonance effect H2O H CH3OH CH3O ~15.5 + H3O+ sp3 C O C F H2O + H3O+ ~12.4 CF3 CH2OH CF3 CH2O H inductive effect F • the inductive effect normally stabilizes the conjugate base alkoxide anion Recall the Effect of alkyl groups as substituents: Stabilization of positive charges and destabilization of negative charges due to HYPERCONJUGATION and Electron REPULSION Alkyl substituent effect on Cations H C H H C R H primary H methyl R C R R H secondary H R C H C C H R tertiary H H H H H C C H H hyperconjugation - a form of resonance increasing hyperconjugation/stability • alkyl groups stabilize carbocations by hyperconjugation, a form of resonance, hyperconjugation delocalizes electrons and charge, lowers the total energy of the electrons in the cation Alkyl substituent effect on Anions H C H H methyl H C R R H primary C R R H secondary C R tertiary DECREASING stability R H electron repulsion destabilization H C H H H equivalent "resonance" results in electron repulsion C • alkyl groups DESTABILIZE carbanions by electron repulsion, equivalent "resonance" rises the total energy of the electrons in the anion Alcohols Copyright, Arizona State University • Extra methyl groups weakly donate electrons towards the anion pKa ~15.5 ~19.0 H 2O CH3OH ~15.5 ~15.9 H 2O H 2O CH3 CH2OH H 3C H3C CH OH H 2O HO hydroxide + H 3O + CH3O methoxide + H 3O + CH3 CH2O H 3C H 2O H 3C CH O + + Me- donating groups weakly destabilize anion and LOWER solvation of the anion H 3O + H 3O + • The electron donation effect is actually pretty weak in this case, probably more important is that the extra methyl groups also decrease solvation of the conjugate base anions, lowering the propensity of the alcohols to ionize in water, decreasing their acidity What about Real Resonance?: • Similar to alkyl substituent effect, stabilization of positive charges and destabilization of negative charges through pi-conjugation/resonance and electron repulsion, but generally larger magnitude effects! • Substituents can be classed as ELECTRON DONATING or ELECTRON WITHDRAWING when attached to pisystems capable of resonance, depending upon whether they have inductive or resonance effects • Whenever a substituent can have both a resonance effect and also an inductive effect, resonance inevitably wins out over the inductive effect! Alkyl (electron donating) substituents (on a pi-system) again pKa HO O O O O O O O -H + ~9.0 HO -H + weaker ~10.0 acid sp2 O donating substituent Me π-anion weakly DESTABILIZED by hyperconjugation electron repulsion H C H donating substituent H The conjugate base anion is weakly destabilized stabilized by methyl group, which donates weakly by hyperconjugation (special form of resonance) Alkyl groups are WEAKLY donating, because hyperconjugation is a much less effective form of electron donation compared to conventional resonance (below), because the donated electrons are already in a strong sigma bond Me Me Me Stronger Electron Donating substituents (on a pi-system) HO O O O O NMe2 NMe2 NMe2 NMe2 -H + NMe2 π-anion stabilized by inductive effect, but MORE DESTABILIZED by resonance donation effect • The conjugate base pi-anion is resonance DESTABILIZED by the electron DONATING -NMe2 group The resonance donating effect is stronger that any inductive stabilization by the electronegative nitrogen • The -NMe2 group is strongly electron donating to a pi-system Alcohols Copyright, Arizona State University Electron Withdrawing substituents (on a pi-system) stronger acid ~6.0 HO O O O CHO CHO O O -H + withdrawing CHO substituent CHO sp2 H C O H C O π-anion stabilized by BOTH resonance and inductive electron withdrawing effects resonance withdrawal • The conjugate base pi-anion is resonance STABILIZED by the electron WITHDRAWING -CHO group • The -CHO group is electron withdrawing on a pi-system, electron withdrawal occurs by both resonance and inductive effects Inductive substituents (on a pi-system) HO stronger acid ~7.0 O -H O O O + CF3 sp2 withdrawing substituent CF3 CF3 CF3 CF3 π-anion not DIRECTLY stabilized, but inductive effect still important • The conjugate base anion is stabilized by the inductive effect of the -CF3 substituent The substituent does not DIRECTLY stabilize the negative charge (the resonance contributors show that the negative charge is never on the carbon to which the substituent is attached), but the anion is still overall stabilized The stabilization would have been greater with DIRECT stabilization (if the charge was at least partially on the carbon to which the substituent was attached) Summary of Electron Withdrawing/Donating Substituents WHEN ATTACHED TO PI-BONDING SYSTEMS • donating and withdrawing ability measured relative to hydrogen When attached to C(sp2)/Pi-Bonding (Conjugated) Systems such as benzene rings increasing electron donating ability increasing electron withdrawing ability F3C O R C N C HO3S O2N + R4N O R O NH C R H RO C O O CH CH2 R2N C these substituents STABILIZE a negative charge on a benzene ring O C R NH2 NR2 OH OR these substituents DESTABILIZE a negative charge on a benzene ring • distinguishing the D- and W- groups is easier than it looks (no memorization!!) • the donating groups have non-bonding electrons or electrons in pi-bonds that can be used to DONATE to the attached pi-system • just about every other substituent is withdrawing due to the presence of electronegative elements, W- groups NOT have non-bonding electrons on the atoms that is connected to the pi-system Alcohols Copyright, Arizona State University Oxidation/Reduction: Definition (more ) • General Chem Definition - addition and subtraction of electrons • Counting electrons in organic structures is difficult, and so Organic Chemistry has its won Definitions Oxidation: Addition of or replacement by oxygen atoms (or other atoms more electronegative than carbon) OR, removal of hydrogen atoms Reduction: Addition of or replacement by hydrogen OR, removal of oxygen atoms (or other atoms more electronegative than carbon) Examples oxidation (alkene oxidized) oxidation (alcohol oxidized) Br Br Br Br H reduction OH O CrO3 H removed from C O H2SO4 H NaBH4 H O EtOH H Br H Br H OH H3O+ Br added to C Br is more electronegative than carbon H added NEITHER oxidation or reduction (1 H, Br added to C) NEITHER oxidation or reduction (1 H, O added to C) • oxidizing agents are usually Lewis acids (accept electrons) and reducing agents are usually Lewis bases (donate electrons) In this way organic oxidation and reduction connects to the general chemistry definition of addition (reduction) and removal (oxidation) of electrons Preparation of Alcohols (more ) 4.1 Review of Reactions We Have Already Seen Recall Hg(OAc)2 / H2O HO NaBH4 H BH3 THF -OH/H2O2 O Alcohols (±) H2 Anti-Markovnikov Syn-addition HO H OH Pd/C Markovnikov Anti-addition adds H to BOTH C=C and C=O bonds Copyright, Arizona State University 4.2 Hydride Reduction of the Carbonyl Group How you this selective reduction of ONLY the C=O bond?? O OH ??? (±) X C C LB H LB + LA "end" O LB "end" • a Lewis base (e.g hydride anion) tends not to react with another Lewis base, and so does nto eract with the alkene, but DOES react with the carbonyl (C=O) group, which can act as a Lewis acid Some (new) reagents electrons not in bond, very reactive Na Li Al larger, electrons in weaker Al-H bond B smaller, electrons in stronger B-H bond Na decreasing electron pair energy Sodium Hydride (NaH) very reactive H H H Al H H Lithium Aluminum Hydride (LiAlH4) "masked hydrides" less reactive, more useful H H B H H Sodium Borohydride (NaBH4) least reactive, most selective In principle H LB H X H H O O LA OH H reduction accomplished (±) • both hydride anion and the alkene are nucleophiles (Lewis bases), thus no reaction there in practice • NaH is too reactive and too strong a Bronsted base (less selective), NaH will usually deprotonate an aldehyde/ketone rather than add to the C=O bond, LiAlH4 or NaBH4 used instead O OH NaBH4 LA (±) EtOH H O H B H LA/BA H O LB H Et H LB/BB – – • BH4 less reactive than H because the electrons are in a bond, therefore lower in energy – – + – + • Overall, BH4 supplies H , EtOH supplies H Together H and H make H2! Example (stereochemistry ignored) OH HO Alcohols LiAlH4 H3O+ O O EtOH O NaBH4 OH O O Copyright, Arizona State University Why does the NaBH4 reduce the ketone and not the ester, and the LiAlH4 reduce both? • The less reactive NaBH4 reduces aldehydes and ketones but not esters • The more reactive LiAlH4 also reduces esters (and acids) – – • The (H3Al-H) bond is weaker than the (H3B–H) bond, and so is more reactive • Esters and acids are less reactive than aldehydes and ketones due to better resonance stabilization LB O O O O LB O O • minor resonance structures Emphasize the Lewis acid character on the carbonyl carbon in a ketone, a LB will react FASTER with an aldehyde and ketone • minor resonance structures DEmphasize the Lewis acid character on the carbonyl carbon in an ester, a LB will react SLOWER with an ester • Alternatively……… weak donating R O C simple π-system LB R STRONG donating more reactive O O C R LB less reactive We can consider that C=O to be a simple pi-system (the same way that a benzene ring is a larger pi-system), and the ester has a string donating group attached to the carbon of the C=O, which decreases its reactivity towards a Lewis base/nucleophile, aldehydes/ketones have only weak donating groups attached to the carbon of the C=O group, they are more reactive To reduce the less reactive esters, the more reactive LiAlH4 is required More on LiAlH4 – • The AlH4 ion will react violently with water and alcohols, so the proton has to be added in a second ACID + WORKUP step, hence the notation: LiAlH4 H3O • in this second acid workup step, just enough dilute acid is used to "complete" the reaction • the protonation is essentially instantaneous, i.e this is NOT the same as acid catalyzed addition of water to an alkene (for example), which requires higher concentrations of acid, a lot of time and usually some heat LA O addition OR H H Al H LB H O elimination OR favored H by entropy LA O H + leaving group OR H LA/BA O H O H H LB/BB H H H Al H LB H OH H H • this is our first example of an addition/elimination mechanism, we will see this again later • note REMOVAL of the -OR group of the ester in the elimination step • elimination occurs here because the -OR is a reasonable leaving group (but not great!), AND elimination at this point is favored by entropy Alcohols Copyright, Arizona State University Examples (stereochemistry ignored) O MeO MeO O NaBH4 O EtOH OH HO H LiAlH4 H3O+ OH • NaBH4 reacts ONLY with the aldehyde • LiAlH4 reacts with the aldehyde AND the carboxylic acid (the acid reaction proceeds via addition/elimination) • The H3O+ in the LiAlH4 reaction does NOT react with the alkene, because in this context, H3O+ means an "acid workup step", which in turn means "add just enough dilute aqueous acid to protonate the negatively charge oxygen atoms" When acid catalyzes water addition to the C=C bond of an alkene the acid concentrations are high, the reaction time is long and the temperature has to be high, the context defines the meaning of H3O+ Reactions of Alcohols (more ) 5.1 Oxidation remove H atoms R CH2 OH R oxidation O add oxygen atom C H aldehyde alcohol O R C further oxidation OH carboxylic acid Question Which product you get, how to control? Answer Determined by the particular alcohol and the reaction reagents/conditions New Cr(VI) Reagent #1 O HO Cr OH Na2Cr2O7 + H2SO4 + Na+ –HSO4 O chromic acid sodium dichromate • the reagent is sodium dichromate and sulfuric acid dissolved in water, this generates chromic acid "in situ" H2O Example with a SECONDARY Alcohol • oxidation to form a KETONE R R' C H OH R' don't have to know!!! chromate ester H O O + H+ HO Cr OH2 HO Cr OH O O Alcohols R Na2Cr2O7/H2SO4/H2O O H R R' C H C O O ketone product O Cr OH O – H+ O R R' C O Cr OH H H O Copyright, Arizona State University Example with a PRIMARY Alcohol • oxidation to form a carboxylic acid THE overall process is as follows: H R C H OH Na2Cr2O7 H2SO4 H R C O aldehyde H2O OH H3O+ C H OH R Na2Cr2O7 H2SO4 H2O hydrate R OH C O acid details, first, formation of the aldehyde via the same mechanism as above H R C H OH Na2Cr2O7/H2SO4 H R C O H2O Osame as before, don't need to know!! H HO Cr OH R C O O H + H+ H O O HO Cr OH2 O – H+ H O Cr OH O O H R C O Cr OH H H O more details, second, conversion of the aldehyde into the hydrate in the presence of water and an acid catalyst, you DO NEED TO KNOW THIS MECHANISM Remember, the reaction conditions involve sulfuric acid in water, the next step is simply acid catalyzed addition of water to the aldehyde H R H H O H H R C OH hydrate OH Na2Cr2O7/H2SO4 C O H2O H H O R C H H O H H O H R C H OH O H final detail, third, conversion of the hydrate (a geminal di-alcohol) into a carboxylic acid, via the same mechanism as before (not shown this time) OH R C H OH Na2Cr2O7/H2SO4 H2O • the hydrate gets oxidized to a carboxlic acid because it is now a (di) alcohol Alcohols Copyright, Arizona State University Example with a TERTIARY Alcohol R R1 Na2Cr2O7/H2SO4/H2O R R1 O O Cr O OH O R2 HO Cr OH O no hydrogens to eliminate, 3° alcohols can not be oxidized! C OH R2 C • tertiary alcohols can not be oxidized, the necessary hydrogen atom is missing OH 1° 2° 3° R R R C H OH C R OH H R C R H O -H2 H C R R OH O -H2 R C C OH OH -H2 R H C O no hydrogens to eliminate, can't oxidize a ketone R X no hydrogens to eliminate, can't oxidize X • for the same reason, ketones can not be oxidized, the necessary hydrogen atom is missing New Cr(VI) Reagent #2 CH2Cl2 CrO3 + HCl + N pyridine O H N Cl Cr O O pyridinium chlorochromate (PCC) • NO WATER here, so any aldehydes that are formed cannot make a hydrate, so further oxidation to a carboxylic acid will not occur • PCC with a PRIMARY Alcohol H R C OH H PCC H CH2Cl2 R C O no water, no hydrate formation aldehyde stable product! don't need to know!!! O HO Cr Cl O O H O H –H+ R C O Cr OH R C O Cr OH H H O O H N Alcohols 10 Copyright, Arizona State University Summary of Oxidation Reactions Na2Cr2O7 H2SO4/H2O PCC/CH2Cl2 R CH2 OH 1° alcohol Carboxylic Acid Aldehyde R R' CH OH 2° alcohol Ketone Ketone 3° alcohol no reaction! no reaction! aldehyde via the hydrate Carboxylic Acid no reaction! R R R' C R'' O C OH H Examples HO Na2Cr2O7 H2SO4/H2O H O acid C OH acid O O OH H PCC/CH2Cl2 O no reaction here Na2Cr2O7 H2SO4/H2O HO aldehyde C H O HO O OH HO O PCC/CH2Cl2 5.2 Formation of Alkyl Halides Substitution reaction: is this possible?? R CH2 OH SN2 LA R CH2 X + OH X LB – – • doesn't work! in fact, goes in reverse OH will substitute for X (think standard SN2 reaction ) – OH is too poor a leaving group, need to make a better leaving group! Reactions with Haloacids, HCl, HBr, HI, etc R LB/BB C OH H Br LA/BA R C OH2 R water, good leaving group LA C Br LB R C Br • this is better, we have seen strategies like this before • however, SN1 mechanism for 2° and 3° alcohols, thus, still the usual problem with the cation intermediate, elimination, rearrangements etc • SN2 mechanism for 1° alcohols, but still, the halide anions are poor nucleophiles, something better is needed Alcohols 11 Copyright, Arizona State University Reaction with PBr3 (phosphorous tribromide) R' C OH H LB R Br P Br Br R Br LA R' Br C O P H H Br SN2 R R' C H Br • SN2 mechanism works well with both 2° and 1° alcohols due to better leaving group, good reaction • only problem is 3° halides, which still don't work well for for steric reasons (recall, no SN2 at 3° centers!) Reaction with SOCl2 (thionyl chloride O R' S R C OH Cl Cl H LB LA R R' C H O H Cl S O Cl R addition elimination R' C H O H S Cl O Cl R Cl R' C H O S Cl SN2 O R R' C H Cl + SO2 + Cl • we will see that many reactions that form small stable molecules, such as SO2, are fast and exothermic • again, SN2 mechanism works well for 1° and 2° alcohols, avoids cation intermediates, good reaction • again, only problem is no SN2 in 3° alcohol case Reaction Summary: Chloride Bromide 1° alcohol SOCl2 PBr3 2° alcohol SOCl2 PBr3 3° alcohol HCl HBr Preferred Reagents 5.3 Formation of Tosylate Esters Why are Tosylates Useful? try this substitution reaction: R R OH Nu + – OH Poor leaving group, therefore difficult to Nu = nucleophile now try this one: R OH2 R Nu + H2O Good leaving group, works if Nu can tolerate acid Nu finally this one: O CH3 R O S O tosylate (ester) Nu Alcohols R Nu + 12 O O S O CH3 tosylate anion, excellent leaving group, works under lots of conditions, this is why tosylates are useful! Copyright, Arizona State University – Where tosylate (esters) come from? R–OH alcohol R O + pyridine Ts–Cl tosyl chloride O Cl S O H R CH3 R–OTs tosylate (ester) O O S H O = N O R O S O CH3 pyridine organic base CH3 + N H N • pyridine is required to remove the proton O S O CH3 O O S CH3 "Tosylate" group = -OTs O (para-toluenesulfonate) "Tosyl" group = -Ts Example useful reactions TsCl pyridine HO weak nucleophile TsO Na+–OCH3 Na+ –Br NH3 Na+ –CN Br N H3CO weak nucleophile H3N C 5.4 Dehydration (a Review) Recall OH H3C C CH3 conc H2SO4 H Δ CH3 CH3 C C O CH3 C C H + CH3 H2O Compare, Pinacol Rearrangement H3C OH OH C C CH3 CH3 CH3 H2SO4 H2O H3C CH3 CH3 + H2O removal of water • Let's treat this as a mechanism problem, how to solve it and what basic principles can we use to guide us? • Look carefully at the reagents/conditions (in this case, acid in water) • Look for differences in start and end structures • Need to remove –H and –OH and an alkyl shift • Acid catalyzed, therefore protonate first, no anionic intermediates in presence of acid Alcohols 13 Copyright, Arizona State University Mechanism OH OH H3C C C CH3 CH3 CH3 H O H H 3C H O CH3 C C –H removed OH OH2 OH CH3 H 3C C C CH3 H3C C C CH3 CH3 CH3 CH3 –OH removed CH3 CH3 H H OH CH3 methyl shifted H 3C C C CH3 CH3 H 3C O H O CH3 C C CH3 CH3 • protonate to make a good leaving group (H2O) • usual carbocation rearrangement to make a more stable (resonance stabilized) cation intermediate • Deprotonation at the end regenerates the acid catalyst Example Mechanism Problem: "Hidden" Pinacol rearrangment HO O HCl / H2O OH H H O H H HO OH HO OH O H OH2 Alcohols 14 Copyright, Arizona State University Alcohols : Summary of Reactions (more ) Hg (OAc)2/H2O OH NaBH4 CH3 BH3.THF CH3 H2O2 / HO– OH H2 O OH NaBH4 EtOH H2 O (±) OH Pd/C or Pt or Raney Ni O (±) OH (±) Pd/C O LiAlH4 O citronellol (from rose oil) PCC CH2Cl2 testosterone O CH3(CH2)8CH2OH Na2Cr2O7 H2SO4 / H2O Na2Cr2O7 O H OH 3° OH OH Cl O Br HCl Cl HBr Br conc H2SO4 Alcohols O SOCl2 pyridine OH CH3(CH2)8CO2H OH TsCl citronellal O H2SO4 / H2O PBr3 OH OH O C H O PCC CH2Cl2 OH 3° OH H3O+ CH2OH O (±) O O S O CH3 heat 15 Copyright, Arizona State University [...]... that many reactions that form small stable molecules, such as SO2, are fast and exothermic • again, SN2 mechanism works well for 1° and 2° alcohols, avoids cation intermediates, good reaction • again, only problem is no SN2 in 3° alcohol case Reaction Summary: Chloride Bromide 1° alcohol SOCl2 PBr3 2° alcohol SOCl2 PBr3 3° alcohol HCl HBr Preferred Reagents 5.3 Formation of Tosylate Esters Why are... this as a mechanism problem, how to solve it and what basic principles can we use to guide us? • Look carefully at the reagents/conditions (in this case, acid in water) • Look for differences in start and end structures • Need to remove –H and –OH and do an alkyl shift • Acid catalyzed, therefore protonate first, no anionic intermediates in presence of acid Alcohols 13 Copyright, Arizona State University...Summary of Oxidation Reactions Na2Cr2O7 H2SO4/H2O PCC/CH2Cl2 R CH2 OH 1° alcohol Carboxylic Acid Aldehyde R R' CH OH 2° alcohol Ketone Ketone 3° alcohol no reaction! no reaction! aldehyde via the hydrate Carboxylic Acid no reaction! R R R' C R'' O C OH H Examples HO Na2Cr2O7 H2SO4/H2O... elimination, rearrangements etc • SN2 mechanism for 1° alcohols, but still, the halide anions are poor nucleophiles, something better is needed Alcohols 11 Copyright, Arizona State University Reaction with PBr3 (phosphorous tribromide) R' C OH H LB R Br P Br Br R Br LA R' Br C O P H H Br SN2 R R' C H Br • SN2 mechanism works well with both 2° and 1° alcohols due to better leaving group, good reaction... in reverse OH will substitute for X (think standard SN2 reaction ) – OH is too poor a leaving group, need to make a better leaving group! Reactions with Haloacids, HCl, HBr, HI, etc R LB/BB C OH H Br LA/BA R C OH2 R water, good leaving group LA C Br LB R C Br • this is better, we have seen strategies like this before • however, SN1 mechanism for 2° and 3° alcohols, thus, still the usual problem with... O H OH2 Alcohols 14 Copyright, Arizona State University 6 Alcohols : Summary of Reactions (more ) 1 Hg (OAc)2/H2O OH 2 NaBH4 CH3 1 BH3.THF CH3 2 H2O2 / HO– OH H2 O OH NaBH4 EtOH H2 O (±) OH Pd/C or Pt or Raney Ni O (±) OH (±) Pd/C O 1 LiAlH4 O citronellol (from rose oil) PCC CH2Cl2 testosterone O CH3(CH2)8CH2OH Na2Cr2O7 H2SO4 / H2O Na2Cr2O7 O H OH 3° OH OH Cl O Br HCl Cl HBr Br conc H2SO4 Alcohols... group, works if Nu can tolerate acid Nu finally this one: O CH3 R O S O tosylate (ester) Nu Alcohols R Nu + 12 O O S O CH3 tosylate anion, excellent leaving group, works under lots of conditions, this is why tosylates are useful! Copyright, Arizona State University – Where do tosylate (esters) come from? R–OH alcohol R O + pyridine Ts–Cl tosyl chloride O Cl S O H R CH3 R–OTs tosylate (ester) O O S H