organic chem reactions, Study notes of Chemical Experimentation

Download organic chem reactions and more Study notes Chemical Experimentation in PDF only on Docsity! Addition of Excess Alcohol and H+ to form Acetals -Must be excess (XS) alcohol, in this class use ethanol Can be written as: -Ethanol (XS), H+ -CH3CH2OH (XS), H+ - ***NOTE: Acetals DO NOT react in base, it’s base stable! OH (XS), H+ H O H RO ORROH (XS), H+ acetal Addition of Water to form Hydrate -Can be done from aldehydes or ketones -Can use NaOH/H2O or H3O+ instead of water also H HO OH hydrate H O H2O or NaOH/ H2O or H3O+ aldehyde O ketone Aldehyde Oxidation using Silver Nitride and Base -Oxidizes aldehydes to carboxylic acid -Ag ion reduces to Ag0 R H O Ag (NO3) NH3/ OH R OH O carboxylic acid Ag0 Addition of Alcohol to form Hemiacetal -In this class use ethanol H HO ORR—OH hemiacetal H O Adol Reaction -Nucleophile = enols (if in acid) / enolates (if in base) -Electrophile = carbonyls -THe nucleophile will attack the electrophile -Step 1: Depronation of alpha carbon -Step 2:aldol addition and protonation **Conjugated [roduct is prefered and defined by cold reactant H HH + O O O OH C—C bond formed H O H O + 1.) NaOH 2.) H2O H O OH nucleophile electrophile beta-hydroxy dicarbonyl H + O H OH 1.) H+ 2.) H2O H O alpha, beta-unsaturated carbonyl O O NaOH / H2O / Heat NR Acetals in Basic Conditions -Acetals DO NOT react in basic conditions -Acetals are base stabilized O OCH3 NaOH / H2O / Heat NR Aminolysis -Amino = NH2 Follows the nucleophilic carbonyl substitution mechanism -Can react with ammonia, 1 ° or 2 ° amine -Makes amides R Cl O R2NH R N R' O R' amide R Cl O R Cl O R’—NH2 R Cl O R’2—NH R’2—NH R OR O HNR’2 H+/ Δ NH3 NH3O O R O R O O R NH2 O R NH O R' R N R' O R' amide R NR’2 O R OH O + NR HO NH2 O O HO NH2 O O + Bromination of Benzene -Electrophilic aromatic substitution -Forms benzyaldehydeBr2 FeBr3 H O R R mCPBA R R O R R O R H O mCPBA mCPBA R O O R ester epoxide R OH O carboxylic acid O O O mCPBA O O O mCPBA O O major Baeyer-Villiger Oxidation -Uses mCPBA -Turns alkenes —> epoxides -Turns ketones —> esters -Turns aldehydes —> carboxylic acids ***NOTE: If mCPBA is used on asymmetric ketone, then the ester forms on the more substituted (big) side H O O H O mCPBA fumate ester H O mCPBA O H O O mCPBA O O O mCPBA O O Carboxylic Acid Synthesis -Jones turns 1 ° OH —> C.A. -O3 & ROOR turns alkene —> C.A. -CO2 & H3O+ turns R-MgX and R-Li —> C.A. OH R OH O carboxylic acid Jones 1.) O3 2.) ROOR R MgX R Li 1.) CO2 2.) H3O+ R OH2 O R OH O R OH O H O NaOH Δ O O OH Cannizaro Reaction - Base induced disproportionation which means reduction and oxidation occurs at same time - Limited to benzaldehydes Clemmenson reduction - Uses to reduce aldehydes or ketones to alkanes using HCl and Zn0/ Hg0 -Occurs under acidic conditions O H HZn0/ Hg0/HCl Decarboxylation -Removes carboxylic acid -Know just 3 ways using H+ and ΔR OH O O H+ Δ R CH3 O CO2 Beta-Keto Acid R OH O O H+ (or H3O+) Δ R H C O CO2 R O O O H+ (or H3O+) Δ R O H HO OH OO H+ (or H3O+) Δ HO CH3 O malonic acid CO2 O O OO Deuterated Chlorine (DCl) and Heavy Water (D2O) Reaction -DCl acts like HCl aka acts as an acid -DCl will turn carbonyl into an enol -It will not stop turning all H into D until all are gone -D2O will result in the same thing O O OH O D D D D DDCl H2/deuterium O D2O OD O D D D D Diisobutylaluminum Hydride (DIBAL-H) -Has (- # ° C) because it prevents over reduction 1.) DIBAL / 2.) H2O -Reduces a lot of things to aldehydes 1.) DIBAL / 2.) H2O/ HCl -Reduces nitrile to imines, then hydrolyzed by acid to amine O OH carboxylic acid H3CO O ester R H O aldehydes 1.) DIBAL 2.) H2O 1.) DIBAL 2.) H2O/ HCl N nitrile H O R Cl O acid chloride R O R O O anhydride R OR O R N R' O R' amide esters R N nitrile 1.) DIBAL (-78 ° C) 2.) H3O+ R H O aldehyde 1.) DIBAL (-78 ° C) 2.) H3O+ R H O aldehyde 1.) DIBAL (-78 ° C) 2.) H3O+ R H O aldehyde 1.) DIBAL (-78 ° C) 2.) H3O+ R H O aldehyde 1.) DIBAL (-78 ° C) 2.) H3O+ R H O aldehyde + R’—OH O Base Acid OH O Enol vs. Enolate -Carbonyls exists in 2 tautomerized forms: keto and enol -Depending on if the keto is reacted with base or acid, it can form a enolate or enol -Enolates are nucleophiles enol enolate Fishcher Esterification -Usually consists of an alcohol and acid catalyst (H+) and heat -H2SO4 and TsOH can also be used as an acid catalyst R OH O carboxylic acid R-OH acid catalyst R OR O ester H2O OH O OH H+ O O OH O CH3OH H2SO4 OCH3 O HO OH O O O H+ HO OH O O O H2SO4 (cat.) Δ HO OH O O CH3CH2OH (2 equiv.) CCl4, Δ O O O O Haloform Reaction -A reaction with methyl ketone -Converted to a carboxylic acid and haloform R= H, alkyl, aryl X= Cl, Br, I O O O X2 Base (OH) + HCX3 R CH3 O X2 Base (OH) R O O + CHX3 Halogenation -Occurs when one or more halogens are added to a substanceH O X2 H+ H OH XO Br2 H+ O Br O Br2 H+ Br O O + Br Hydroboration 1.) BH3 . THF 2.) H2O2, KOH -Anti-Markovnikov -Syn addition on same side —> —> - Creates a bond with OH on it too -Hydroboration alone makes alkylborane CH3 H OH CH3 1.) BH3 . THF 2.) H2O2, KOH 1.) BH3 . THF 2.) H2O2, KOH O H Hydroboration 1.) BH3 . THF 2.) H2O2, KOH -Anti-Markovnikov -Syn addition on same side —> —> - Creates a bond with OH on it too -Hydroboration alone makes alkylborane 1.) BH3 . THF 2.) H2O2, KOH OH R Cl O acid chloride R O R O O anhydride R OR O R N R' O R' amide esters R N nitrile 1.) BH3 THF 2.) H3O+ R OH R OH + R’—OH R N R’ H H R’ R NH2 amide NR 1.) BH3 THF 2.) H3O+ 1.) BH3 THF 2.) H3O+ 1.) BH3 THF 2.) H3O+ 1.) BH3 THF 2.) H3O+ R Cl O H2O R OH O + HCl O H3O+ Δ O + ’R OH O O O H2O OH OH O O + Hydrolysis Methods -Can use water, hydronium ion w/ heat or Saponification -Regardless of method there will be a tetrahedral intermediate ***Note, these are examples are of esters R O R’ H3O+ Δ R OH + ’R OH O O H3O+ Δ HO OH O lactone O O H3O+ Δ OR O EtOH+ R N R' O R' H3O+ Δ R OH O H2NR’2+ NH4R N H3O+ Δ R OH O + Hydrolysis Mechanism - Can only be done with the hydronium ion (H3O+) in most cases - Hydrolysis happens when there are two oxygens separated by a bond - H30+ pronates O and gives it a + charge which then leads to rearrangement —> rings can open to form chains O O HO H O H3O+ H2O H H O O HO O H2O HO H OH HO H O H H2O Lithium Aluminum Hydride (LAH) Reduction -Strong reducing agent -Consists of LiAlH4 and H3O+ Reducing agent w/ H3O+ -Reduces carboxylic acid —> 1° OH -Reduces ester —> 1° OH -Reduces aldehyde —> 1° OH -Reduces ketone —> 2° OH -Reduces epoxide —> 2° OH ***LAH on alcohol does nothing because it just reforms an alochol again R OH O carboxylic acid OH 1.) LiAlH4 2.) H3O+R O O R ester R H O aldehyde 1° OH Lithiates/ Organolithium - Reduces to alcohols by reacting with electrophilic carbonyls R R O R H O H H O 1.) R’—Li or R—MgX 2.) H3O+ 1.) R’—Li or R—MgX 2.) H3O+ 1.) R’—Li or R—MgX 2.) H3O+ R R OH R' R R' OH ’R OH Knoevenagel Condensation Reaction -Forms a ring -Consists of 2 parts Michael Addition Aldol Condensation -The aldol condesation is intramolecular -Creates a 6-membered ring containing a alpha-beta unsaturated ketone RO OR O O ’R R” O Base (R—O) RO OR O O ’R R’ R R O epoxide 1.) LiAlH4 2.) H3O+ OH R R O ketone 2 ° OH R Cl O acid chloride R O R O O anhydride R OR O R N R' O R' amide esters R N nitrile 1.) LAH 2.) H3O+ R OH 1.) LAH 2.) H3O+ 1.) LAH 2.) H3O+ 1.) LAH 2.) H3O+ 1.) LAH 2.) H3O+ R OH2 R OH + R’—OH R N R’ H H R’ R NH2 amide OH OH 1.) LAH 2.) H3O+ O LAH H3O+ O LDA THF, -78 ° C OLi O 1.) LDA 2.) R—Lg O + Li—Br N H Lithium Diisopropylamide (LDA) -LDA is a strong, bulky base -Forms enolates LDA remove proton selectively from carbon -Can deprotonate alpha proton w/o help -LDA will not attack carbonyls, esters, and nirtiles b/c it’s a nuclear base O LDA O Methylamine with Hydrogen Ion to form Imine - CH3NH2, H+ - Turns =O —> Imine Imine written as: R H N R R N R O N CH3NH2, H+ R N R R Metallic Magnesium or Magnesium Metal (Mg0) -Adds Mg in front of Br on a chain or other alkyl halide If followed by: -H3O+ then it pronates, usually used instead of CO2 if there is already a carbonyl present, - 1.)CO2(s) & 2.) H3O+ then MgBr turns to carboxylic acid BrMg H HO H O Mg0 CO2, H30+ Mg0 H30+ O O H2O H OH Br + Nitrile Synthesis -Nitriles can be formed using -POCl3, P2O5, or SOCl2 to dehydrate 1° amide -Cynanide Ion or NaCN on bromide using SN2 R NH2 O POCl3 R N nitrile 1° amide R NH2 O SOCl2 R N nitrile 1° amide R OH R LG NaCN R N nitrile CHNH nitrile R N *adds one carbon R NH2 O P2O5 R N nitrile 1° amide Oxalyl Chloride -Found in Swern reaction -Changes OH on carboxylic acid to Cl -Same thing happens using Phosphorus Pentachloride (PCl5) R OH O carboxylic acid Cl Cl O O R Cl O OH O PCl5 Cl O benzoic acid benzoyl chloride R R OH 1.) oxayl chloride, DMSO 2.) Et3N R R O Ozonalysis -Oxidant -Cleaves alkenes into carbonyls aka a ketone and aldehyde 1.) O3 2.) Me2S H O O + Oxidation from Aldehyde to Caboxylic Acid - Oxidize aldehyde to carboxylic acid - Reduces Ag ions to Ag metalsR H R OH O O Ag(NO3) NH3 / OH Ag0 Perkin Alicyclic Synthesis -Used to make cinnamic acids -Results in an alpha, beta- unsaturated aromatic acids via aldol condensation of an aromatic aldehyde and acid anhydride -Occurs in presence of alkali salt of acid -Alkali salt acts as base catalyst Phophorus Pentoxide Reaction (P2O5 / P2O10) -Forms anhydrides when it dehydrates carboxylic acids -Amide can react via elimination to form nitriles R OH O 2 P2O5 or P2O10 O O O R NH2 O P2O5 R N PCC (weak oxidizer) -1 degree OH —> aldehyde -2 degree OH —> ketone OH R H O OH O 2° OH —> ketone 1° OH —> aldehyde PCC PCC Potassium Permanganate -Reaction will only work if H is attached to carbon -Oxidation wll result in benzoic acid KMnO4 OH O KMnO4 OH O OH O KMnO4 NR Reductive Amination -All uses two steps, step 2 is the same for all using Sodium Borohydride and H3O+ -Carbonyl —> 2 ° amine - Step 1: R-NH2/ H+ -Carbonyl —> 1 ° amine - Step 1: NH3 -Carbonyl —> 3 ° amine - Step 1: R2-NH/ H+ R-NH2 H+ NaBH4 H3O+R R N R R HN R' 2 ° amine R R O NaBH4 H3O+R R NH R R NH3 1 ° amine NH3 NaBH4 H3O+ 3 ° amine R2-NH H+R R O R R NR2 R R N ’R R' Retro-Adol Reaction -Reaction where beta-hydroxy carbonyl decomposes into an aldehyde or ketone H O OH H H + O O C—C bond breaks R R R O Rosenmund Reaction -Catalytic hydrogenation of acid chlorides -Reduction forms aldehydes -Selects for acyl chloridesR Cl O acid chloride H2 Pd, BaSO4 R H O aldehyde + HCl Sodium Borohydride & H3O+ Reduces Imines to Amines - NaBH4 and H3O+ - Imine —> Amine Note the differences: Amine Amide Imine Enamine NH2 O NH2 H N NH2 N HNNaBH4 H3O+ N H O H H O N OH NH NaBH4 H3O+ 2 ° amine NH NR2 NaBH4 H3O+ NaBH4 H3O+ N NH2 R Cl O acid chloride R O R O O anhydride O NaBH4 NR NaBH4 R OH R OH O + Sodium Borohydride -Of the following, it only reacts with anhydrides R OR O R N R' O R' amide esters R N nitrile NaBH4 NaBH4 NaBH4 NR NR NR Sodium Cyanoborohydride - No reaction on carboxylic acid or carbonyls in general -Is selective in reducing imines to to 2 ° amineR OH O 1.) NaCNBH3 2.) H3O+ NR carboxylic acid N O 1.) NaCNBH3 2.) H3O+ NH O R Cl O NaCNBH3 NR acid chloride R O R O O NaCNBH3 NR anhydride R OR O NR 1.) NaCNBH3 2.) H3O+ (cold) esters R N R' O R' amide NR 1.) NaCNBH3 2.) H3O+ R N NR 1.) NaCNBH3 2.) H3O+nitrile Stork Reaction -Cyclohexane is reacted with piperidine to form an enamine -Once enanmine is formed, hydrolyze it by doing an SN2 reaction and get pronated by H3O+ to make alkylated carbonyls O N H H+ N N R Lg SN2 Enamine N R H3O+ O R Stork Enamine Alkylation (Michael-Stork) Addition -Enamines add to alpha, beta- unsaturated carbonyls (Michael acceptor) O R2NH/ H+ N R R O1.) O O 2.) H3O+ O N R R Wittig Reaction -Reacts aldehyde or ketone with ylide to form alkeneR R O R R' PØ3 O H H PØ3 CH2 Symmetrical ylide O H H3C PØ3 Asymmetrical ylide H ylide alkenealdehyde or ketone H O H H PØ3 H CH2 Symmetrical ylideAsymmetric carbonyl H O Asymmetric carbonyl H H3C PØ3 Asymmetrical ylide Cis product is major Wolff-Kischner Reduction of Carbonyls to CH2 -Same results as Mozingo and Clemmenson reduction -Forms imine intermediate that then reduces to CH2 -Uses hydrazine, heat and KOH R R O H HH2N-NH2 KOH/ Δ alkane Ylide Formation - 1 SN2 step that reacts a primary or secondary methyl halide with triphenol phosphine -Further react with butyl lithium to form reactive ylide R R Br PØ3 SN2 R PØ3 R’ H Li R R' PØ3reactive ylide