Surya K. De - Applied Organic Chemistry

18 10 Synthesis of Some Heterocyclic Compounds Using Named ReactionsBartoli Indole Synthesis Bischler–Napieralski Reaction Combes Quinoline Synthesis Conrad–Limpach Synthesis Doebner–Miller Reaction Feist–Benary Synthesis of Furan Fischer Indole Synthesis Friedländer Synthesis or Annulation Knorr Pyrrole Synthesis Madelung Indole Synthesis Paal–Knorr Furan Synthesis Paal–Knorr Pyrrole Synthesis Pictet–Gams Isoquinoline Synthesis Pictet–Spengler Reaction Skraup Quinoline Synthesis References Bischler–Napieralski Reaction Combes Quinoline Synthesis Conrad–Limpach Synthesis Doebner–Miller Reaction Feist–Benary Synthesis of Furan Fischer Indole Synthesis Friedländer Synthesis or Annulation Knorr Pyrrole Synthesis Madelung Indole Synthesis Paal–Knorr Furan Synthesis Paal–Knorr Pyrrole Synthesis Pictet–Gams Isoquinoline Synthesis Pictet–Spengler Reaction Skraup Quinoline Synthesis

19 11 Protection and Deprotection of Common Functional Groups Amines Alcohols For 1,2‐Diols For 1,3‐Diols For Phenols Protection and Deprotection for the Carboxylic Acid Group Protection and Deprotection of Carbonyl Group Protection and Deprotection of Terminal Alkyne References Alcohols Protection and Deprotection for the Carboxylic Acid Group Protection and Deprotection of Carbonyl Group Protection for the Terminal Alkyne CH

20 12 Amino Acids and PeptidesNatural Amino Acids Nonnatural Amino Acids Solution‐Phase Peptide Synthesis Solid‐Phase Peptide Synthesis Cleavage Cocktail Cleavage Cocktail A Cleavage Cocktail B Reagents and conditions Covalent Peptides Staple Peptides Building Blocks for Stapled Peptides (Both L and D Analogs of Amino Acids Are Available) References

21 13 Functional Group Transformation Alcohol to Aldehyde Secondary Alcohol to Ketone Primary Alcohol to Carboxylic Acid 1,2‐Diol Oxidation Alcohol to Fluoride [11,14,15] Alcohol to Chloride Alcohol to Bromide Alcohol to Iodide [13] Alcohol to Ester Alcohol to Ether Alcohol to Sulfonic Ester Alcohol to Methylene Alcohol to Azide Azide to Amine Aldehyde to Alcohol Aldehyde to Carboxylic Acid Aldehyde to Difluoro [14, 15] Ketone to Alcohol Ketone to Ester Ketone to Difluoro [14,15] Ketone to Methylene Ketone to Thioketone Acid (Carboxylic) to Ester Acid to Amide Acid to Ketone Ester to Acid Ester to Aldehyde Ester to Alcohol Ester to Ketone Nitro to Amine Alkene to Epoxide Alkene to Alkane Alkyne to Alkane Alkyne to Alkene Cyano to Carboxylic Acid Cyano to Amine [16] Cyano to Amide Methyl Phenyl Ether to Phenol [17, 18] Toluene to Benzyl Halides Alkylbenzene to Benzoic Acid Aromatic Amine to Azide Aromatic Halide to Aldehyde [21] Aromatic Halide to Benzoic Acid [22] Thioether to Sulfoxide Thioether to Sulfone Thiol to Disulfide [23–25] Unsymmetrical Disulfide Reductive Amination Amine to Urea and Thiourea Urea Formation from Two Amines References

22 14 Synthesis of Some Drug Molecules References

23 15 Common Laboratory MethodsAcetylation of Alcohol (patent WO2013040068A2) Deacetylation (patent WO2013040068A2) Tosylation of Alcohol (patent US9399645B2) Benzoylation of Alcohol (patent WO2019093776A1) Pivaloylation of Alcohol (patent WO2019093776A1) Silylation of Alcohol (patent WO1998008849A1) Desilylation (patent WO1998008849A1) Esterification (ester formation) Ester Formation from Acid and Alcohol (patent US9399645B2) Carboxylic Acid to Benzyl Ester (patent WO2019134765A1) Hydrolysis (saponification) of Ester Carboxylic Acid to Acid Chloride (patent US20070197544A1) Acid Chloride to Amide (patent US20070197544A1) Amide Bond Formation Using Carboxylic Acid and PBr3 (patent US20070197544A1) Buchwald–Hartwig Amination (patent US20070197544A1) Ester to Carboxylic Acid (patent WO2019134765A1) Benzyl Ester to Carboxylic Acid (patent WO2019134765A1) Boc‐ Protection of Amino Group (patent US20090054548A1) Deprotection of Boc Group (patent US20090054548A1) Sulfonation of Aromatic Compound (patent WO2002030878A1) Nitration of Aromatic Compound (mild and noncorrosive conditions) (patent WO1994019310A1) Nitration of Aromatic Compound (regular method) Nitration of Aromatic Compound (regular method) (patent WO2016118450A1) Reduction of Nitro Group (patent WO2018167800A1) Reduction of Nitro Group by Hydrogenation (patent US6329380B1) Reduction of Nitro Group Using Hydrazine Raney Nickel (patent US20070197544A1) Reduction of Nitro Group Using Fe and NH4Cl (patent US20070197544A1) Reduction of Ketone with NaBH4 (patent WO2013040068A2) Reduction of Ester to Alcohol (patent US9399645B2) Reduction of Ester to Alcohol with DIBAL‐H (patent WO2016037566A1) Ester to Aldehyde (patent US20190337964A1) Selective Oxidation of Primary Alcohol (patent WO2013040068A2) Oxidation of Alcohol Using DMP Oxidation of Primary Alcohol Using TEMPO (patent US10407378B2) Benzylation of Phenol Debenzylation by Hydrogenation (Patent WO1994028886A1) Iodination of Aromatic Compound (patent US7951832B2) Methylation of Phenol Demethylation to Phenol (patent US6924310B2) Bromide to O‐Benzyl (patent WO2019134765A1) Tosylate to Fluoride (patent WO2019134765A1) Iodide to Tosylate (patent WO2019134765A1) Ozonolysis of Alkene (patent WO2013040068A2) Asymmetric Dihydroxylation of Alkene (Sharpless Method) (WO2019093776A1) Alcohol to Fluoride (WO2019134765A1) Alcohol to Iodide (patent US9399645B2) Alcohol to Bromide (patent WO2016037566A1) Alcohol to Iodide via Tosylation (patent WO2016037566A1) Alkene to Aldehyde (patent WO1998008849A1) Amine to Azide via Diazotization (patent WO20030135050A1) Azide to Amine (patent US6329380B1) Reductive Amination (patent WO2005118525A1) Asymmetric C‐Alkylation (patent WO2005118525A1) Aldehyde to 1,1‐Difluoroalkane (WO2018167800A1) Free Radical Reaction (patent WO2013040068A2) Umpolung Silylation of 1,3‐Dithiane (C‐Silylation) (Model reactions for education purpose only) Alkylation on 2‐Diphenylmethyl‐1,3‐Dithiane Deprotection of 1,3‐Dioxolane Preparation of Grignard Reagent and Reaction with an Aldehyde Alcohol to Bromide Deprotection of 1,3‐Dithiane

24 16 Common Reagents in Organic Synthesis Acetic Acid (CH 3CO 2H) Acetic Anhydride Acetyl Chloride AlkylFluor Aluminum Chloride (Aluminium Chloride; AlCl 3) Aluminum Isopropoxide (Aluminium Isopropoxide) Ammonium Chloride (NH 4Cl) Ammonium Formate Ascorbic Acid (Vitamin C) Sodium Salt (Sodium L‐Ascorbate) 9‐Azabicyclo[3.3.1]nonane N ‐Oxyl, (2‐Azaadamantane‐ N ‐oxyl) (AZADO) Azobisisobutyronitrile (AIBN) [1,1′‐(Azodicarbonyl)dipiperidine] (ADDP) Benzoyl Peroxide [1,1′‐Bis(diphenylphosphino)ferrocene] palladium(II) dichloride, Pd(dppf)Cl 2 [Bis(triphenylphosphine)palladium(II) dichloride], Pd(Ph 3P) 2Cl 2 Bismuth Chloride (BiCl 3) (Bis(trifluoroacetoxy)iodo)benzene 9‐Borabicyclo[3.3.1]nonane (9‐BBN) Boron Tribromide (BBr 3) Boron Trifluoride Diethyl Etherate (BF 3‐OEt 2) Bromine (Br 2) N ‐Bromosaccharin (NBSa) N ‐Bromosuccinimide (NBS) Burgess Reagent [Methyl N ‐(triethylammoniosulfonyl)carbamate] tert ‐Butyldimethylsilyl Chloride (TBDMS‐Cl) tert ‐Butyldimethylsilyl Trifluoromethanesulfonate (TBS‐OTf) tert ‐Butyl Hydroperoxide (TBHP) n ‐Butyllithium ( n ‐BuLi) tert ‐Butyllithium tert ‐Butyl Nitrite (TBN) Carbon Tetrabromide (CBr 4) Carbonyldiimidazole (CDI) Ceric Ammonium Nitrate (CAN; (NH 4) 2Ce(NO 3) 6) Cesium Carbonate (Cs 2CO 3) Cesium Fluoride (CsF) Chloramine‐T, N ‐chloro Tosylamide Sodium Salt m ‐Chloroperbenzoic Acid ( m ‐CPBA) N ‐Chlorosuccinimide (NCS) Chromium Trioxide Cobalt Chloride Copper Iodide (CuI) Dess–Martin Periodinane (DMP) (Diacetoxyiodo)benzene (DAIB) 1,4‐Diazabicyclo[2.2.2]octane (DABCO) 1,8‐Diazabicyclo[5.4.0]undec‐7‐ene (DBU) Diazomethane Di‐ tert ‐butyl Azodicarboxylate (DBAD) 2,3‐Dichloro‐5,6‐dicyanobenzoquinone (DDQ) N , N ′‐Dicyclohexylcarbodiimide (DCC) Diethylaminosulfur Trifluoride (DAST) Diethyl Azodicarboxylate (DEAD) Diiodomethane (CH 2I 2) Diisobutylaluminum Hydride (DIBAL‐H) Diisopropylaminoborane Diisopropyl Azodicarboxylate (DIAD) N , N ‐Diisopropylethylamine (DIEA) (Hünig's Base) 4‐Dimethylaminopyridine ( N , N ′‐Dimethylaminopyridine) (DMAP) Diphenylphosphoryl Azide (DPPA) Di‐ tert ‐butyl Peroxide (DTBP) Ethyl Chloroformate 1‐Ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide Hydrochloride (EDC·HCl) Formic Acid O ‐(7‐Azabenzotriazol‐1‐yl)‐ N , N , N ′, N ′‐tetramethyluronium hexafluorophosphate (HATU) Hexafluorophosphate Benzotriazole Tetramethyl Uronium (HBTU) Hexamethylphosphoramide (HMPA) Hydrazine (NH 2NH 2·H 2O) 1‐Hydroxybenzotriazole (HOBt) Hydrogen Peroxide [Hydroxy(tosyloxy)iodo]benzene (HTIB) (Koser's Reagent) Imidazole Iodine (I 2) Iodobenzene Dichloride N ‐Iodosuccinimide (NIS) 2‐Iodoxybenzoic Acid (IBX) Iron(III) Nitrate Nonahydrate Isoamyl Nitrite (Also Called Amyl Nitrite) Isobutyl Chloroformate Jones Reagent Lawesson's Reagent Lead Tetraacetate (Pd(OAc)4) Lithium Aluminum Hydride (LiAlH 4) Lithium Diisopropylamide (LDA) 2,6‐Lutidine (2,6‐Dimethylpyridine) Manganese Dioxide (MnO 2) Methanesulfonyl Chloride (Mesyl Chloride) N ‐Methylmorpholine N‐oxide (NMO) Nitrosobenzene Osmium Tetroxide Oxalyl Chloride Oxone (Potassium Peroxymonosulfate) Ozone (O 3) PhenoFluor Mix Palladium on Calcium Carbonate (Pd/CaCO 3) Palladium on Carbon Phenyltrimethylammonium Perbromide (PTAB) or Phenyltrimethylammonium Tribromide (PTT) Phosphorus Oxychloride Phosphorus Tribromide (PBr 3) Piperidine Platinum on Carbon Platinum(IV) Oxide Potassium bis(trimethylsilyl)amide (KHMDS) (Potassium Hexamethyldisilazide) Potassium tert ‐Butoxide Potassium Carbonate Potassium Iodide Potassium Permanganate Potassium Sodium Tartrate Tetrahydrate (Rochelle's Salt) Propylphosphonic Anhydride (T3P) PyAOP (Benzotriazol‐1‐yloxy)tripyrrolidinophosphonium Hexafluorophosphate (PyBOP) Pyridine Pyridinium Chlorochromate (PCC) Pyridinium Dichromate (PDC) Pyridinium p‐Toluenesulfonate (PPTS) Raney Nickel Ruthenium(III) Chloride (RuCl 3) Scandium(III) Trifluoromethanesulfonate (Scandium Triflate) Selectfluor Sodium Azide Sodium Bis(trimethylsilyl)amide (NaHMDS) Sodium Borohydride Sodium Cyanoborohydride Sodium Hydride (NaH) Sodium Hypochlorite (Bleach) Sodium Nitrite Sodium Periodate Sodium Sulfide (Na 2S) Sodium Triacetoxyborohydride (STAB) Tetra‐ n ‐butylammonium Fluoride (TBAF) Tetra‐ n ‐butylammonium Iodide (TBAI) Tetrakis(triphenylphosphine)palladium(0) (Pd(Ph 3P) 4) 2,2,6,6‐Tetramethylpiperidin‐1‐yl)oxyl (TEMPO) Tetrapropylammonium Perruthenate (TPAP) Thionyl Chloride Titanium(IV) Chloride Titanium Isopropoxide p ‐Toluenesulfonic Acid Tributyltin Hydride Triethylamine (TEA) Triethyl Orthoformate Trifluoroacetic Acid (TFA) Trimethylsilyl Chloride (TMS‐Cl) 2‐(Trimethylsilyl)ethoxymethyl Chloride (SEM‐Cl) Trimethylsilyl Cyanide (TMS‐CN) Trimethylsilyl Diazomethane Trimethylsilyl Iodide Triphenylphosphine (Ph 3P) Triphosgene [bis(trichloromethyl) carbonate (BTC)] Tris(dibenzylideneacetone)dipalladium(0) Trityl Chloride (Triphenylmethyl Chloride) Urea Hydrogen Peroxide (UHP) Zinc (Zn) Zinc Chloride References Further Reading