An innovative Green An innovative Green Chemistry Methodology for Chemistry Methodology for Selective Aerobic Oxidation Selective Aerobic Oxidation of Primary Alcohols of Primary Alcohols Dr. Nan Jiang Jiang Dr. Nan Prof. Arthur J Ragauskas Ragauskas Prof. Arthur J Department of Chemistry Department of Chemistry Georgia Institute of Technology Georgia Institute of Technology Atlanta, GA 30332 Atlanta, GA 30332 jiangnnan@yahoo.com
Green Chemistry Green Chemistry � prevent waste before prevent waste before � � avoid protecting avoid protecting � created created groups groups � be atom efficient be atom efficient � � use use renewables renewables � � use benign substrates use benign substrates � use catalysts use catalysts � � � make benign products make benign products � � analyze in real time analyze in real time � � use less or benign use less or benign � � make things make things � solvent solvent biodegradable biodegradable � use less energy use less energy � be safe be safe � � P. T. Anasta, J. C. Warner, Green Chemistry: Theory and Practice . Oxford University Press: New York, 1998. jiangnnan@yahoo.com
Atom Economy Atom Economy mass of atoms in desired product × 100% Atom Economy = mass of atoms in reactants Oxidation CrO 2 + + + CHO OH CH 2 Cl 2 C 5 H 5 N·HCl·CrO 3 C 5 H 5 N·HCl + H 2 O PCC Atom efficient 33% Catalyst 0.5 O 2 CHO + H 2 O + OH 85% atom efficient Reduction Catalyst H 2 CHO + OH 100% atom efficient jiangnnan@yahoo.com
Reaction Solvents Reaction Solvents � Molecular Organic Molecular Organic � Alternative Reaction Alternative Reaction � � Solvents Solvents Media Media 1. Volatile Organic Volatile Organic 1. 1. Water or aqueous media Water or aqueous media 1. Compounds (VOCs VOCs): ): Compounds ( 2. Supercritical CO Supercritical CO 2 2. 2 MeOH, , EtOH EtOH, Ether, , Ether, MeOH 3.Poly(ethyleneglycol) 3.Poly(ethyleneglycol) Chlorinated Solvents, , Chlorinated Solvents (PEG) and aqueous PEG (PEG) and aqueous PEG Benzene, etc. Benzene, etc. solution solution 2. High Polar High Polar Aprotic Aprotic 2. 4. Ionic Liquids Ionic Liquids 4. Solvents: DMF, DMA, Solvents: DMF, DMA, DMSO, etc. DMSO, etc. jiangnnan@yahoo.com
Ionic Liquids (ILs ILs) ) Ionic Liquids ( � Definition: Definition: composed entirely of ions with a � composed entirely of ions with a melting point below 100 º ºC. C. melting point below 100 � Properties: Properties: low volatility, high polarity, � low volatility, high polarity, thermal stability, good solubility, ‘ ‘designer designer thermal stability, good solubility, solvents’ ’ by a proper choice of by a proper choice of cation cation and anion. and anion. solvents � ‘ ‘Green Solvents Green Solvents’ ’: : this is highly contentious: � this is highly contentious: 1. they have not been fully tested; 1. they have not been fully tested; 2. some ILs ILs are made from highly toxic ions and are made from highly toxic ions and 2. some could cause great harm when spilt . could cause great harm when spilt . jiangnnan@yahoo.com
Some Ions in Ionic Liquids Some Ions in Ionic Liquids Cations Anions R PF 6 R 2 R 1 N N N + BF 4 + CF 3 SO 3 Imidazolium Pyridinium (CF 3 SO 3 ) 2 N R 2 R 2 R 3 P + R 3 MeOSO 3 N + R 1 R 1 R R AlCl 4 Ammonium Phosphonium Cl(Br) jiangnnan@yahoo.com
Oxidation of Alcohols Oxidation of Alcohols R 1 R 1 Oxidation H O OH R 2 R 2 CrO 2 + PhCHO + PhCH 2 OH + CH 2 Cl 2 C 5 H 5 N·HCl C 5 H 5 N·HCl·CrO 3 + H 2 O PCC Atom efficient 33% catalyst PhCH 2 OH + O 2 + H 2 O PhCHO Atom efficient 85% jiangnnan@yahoo.com
TEMPO Catalyzed Selective Oxidation of TEMPO Catalyzed Selective Oxidation of Primary Alcohols Primary Alcohols 2,2,6,6,-tetramethyl-piperidyl-1-oxy N TEMPO Nitroxy Radical TEMPO O 1 mol% TEMPO PhCH 2 OH + NaOCl + NaCl + PhCHO H 2 O 10 mol% NaBr Atom efficient 58% CH 2 Cl 2 , 0 ºC P. L. Anelli et al J. Org. Chem. 1987 , 52 , 2559. 1 mol% TEMPO/4 mol% Br 2 PhCH 2 OH PhCHO + H 2 O 4-8 mol% NaNO 2 , 0.4 MPa Air CH 2 Cl 2 , 80 ºC Atom efficient 85% X. Hu et al J. Am. Chem. Soc. 2004 , 126 , 4112. jiangnnan@yahoo.com
Transition- -Metal Catalyzed Selective Metal Catalyzed Selective Transition Aerobic Alcohol Oxidation Aerobic Alcohol Oxidation 0.5 mol% Pd(OAc) 2 / PhenS PhCHO N N PhCH 2 OH + H 2 O air (30 bar), 10 mol% NaOAc 2 mol% TEMPO, H 2 O, 100 ºC NaO 3 S SO 3 Na R. A. Sheldon et al Science 2000 , 287 , 1636. PhenS 0.5%RuCl 2 (PPh 3 ) 3 , 1.5 mol% TEMPO PhCH 2 OH PhCHO PhCl, 100 ºC, 1 atm O 2 , 2.5 h R. A. Sheldon et al J. Am. Chem. Soc. 2001 , 123 , 6826. Limitations: unreactive alcohols with heteroatoms ( N , S , O ) jiangnnan@yahoo.com
10 mol% CuCl, 10 mol% TEMPO ArCH 2 OH ArCHO DMF, rt, O 2 , 1-7 h M. F. Semmelhack et al J. Am. Chem. Soc. 1984 , 106 , 3374. 5 mol% [CuBr 2 (2,2'-bipyridine)] RCH 2 OH RCHO 5 mol% TEMPO, 5 mol% t- BuOK MeCN/H 2 O (2:1), rt, Air, 2.5-24 h R. A. Sheldon et al Chem. Commun. 2003 , 2414. R 1 R 1 5 mol%CuCl, 5 mol% TEMPO OH O R 2 [bmim]PF 6 , 65 ºC, O 2 , 15-60 h R 2 I. A. Ansari and R. Gree Org. Lett. 2002 , 4 , 1507. jiangnnan@yahoo.com
Recovery and Reuse of TEMPO Recovery and Reuse of TEMPO 3 mol% acetamido-TEMPO CH 2 OH CHO 6 mol% HBr, 2-4 eq. H 2 O 2 [bmim]PF 6 , 40°C R R up to 92 % Acetamido-TEMPO can be recycled and reused for 5 runs. N N O AcHN N + PF 6 [bmim]PF 6 Acetamido-TEMPO N. Jiang and A. J. Ragauskas Tetrahedron Lett. 2005 , 46 , 3323. jiangnnan@yahoo.com
Can Acetamido Acetamido- -TEMPO Work as TEMPO Work as Can Recyclable Catalyst in Ionic Liquid Recyclable Catalyst in Ionic Liquid for Aerobic Alcohol Oxidation? for Aerobic Alcohol Oxidation? R 1 R 1 acetamido-TEMPO/Cu H O OH additive, O 2 , ILs R 2 R 2 additive = 4-(dimethylamino)pyridine (DMAP) N N DMAP jiangnnan@yahoo.com
Optimization of the Reaction Conditions a ,b Optimization of the Reaction Conditions 5 mol% Cu(II), 10 mol% DMAP MeO CHO MeO CH 2 OH 5 mol% acetamido-TEMPO ILs, O 2 (1 atm), rt, 5 h entry copper salt ionic liquid conversion (%) c yield (%) d [bmim]PF 6 1 52 43 CuCl 2 2 [bmim]BF 4 47 45 CuCl 2 3 [mmim]OSO 3 Me 44 32 CuCl 2 4 87 81 CuCl 2 [bmpy]PF 6 N N N N N + + + [bmpy] [mmim] [bmim] jiangnnan@yahoo.com
4 87 81 CuCl 2 [bmpy]PF 6 [bmpy]PF 6 66 59 Cu(OAc) 2 5 [bmpy]PF 6 6 91 88 CuBr 2 [bmpy]PF 6 99 7 Cu(ClO 4 ) 2 91 - 8 e [bmpy]PF 6 Cu(ClO 4 ) 2 4 - 9 f [bmpy]PF 6 0 Cu(ClO 4 ) 2 - - 10 g [bmpy]PF 6 0 a 2 mmol 4-methoxybenzyl alcohol, 5 mol% acetamido-TEMPO, 5 mol% copper(II) salt, 10 mol% DMAP, 1 atm O 2 , 0.50 g ionic liquid, room temperature for 5 h. b Selectivity is over 99% determined by 1 H NMR of c Conversion by 1 H NMR of the crude the crude product mixture. product mixture. d Isolated yield by flash chromatography. e No DMAP was added. f No acetamido-TEMPO was added. g No copper salt was added. jiangnnan@yahoo.com
a,b Recycling and Reuse of the Catalysts Recycling and Reuse of the Catalysts OMe OMe 5 mol% Cu(ClO 4 ) 2 , 10 mol% DMAP 5 mol% acetamido-TEMPO [bmpy]PF 6 , O 2 , rt CH 2 OH CHO run time (h) conversion (%) c yield (%) d 1 5 99 91 2 5 96 91 3 5 94 92 4 8 93 85 5 8 87 81 a 2 mmol 4-methoxybenzyl alcohol, 5 mol% acetamido-TEMPO, 5 mol% Cu(ClO 4 ) 2 ·6H 2 O, 10 mol% DMAP, 1 atm O 2 , 0.50 g [bmpy]PF 6 , room b Selectivity is over 99% determined by 1 H NMR of temperature. c Conversion by 1 H NMR of the crude the crude product mixture. product mixture. d Isolated yield by flash chromatography. jiangnnan@yahoo.com
Aerobic Oxidation of Alcohols Aerobic Oxidation of Alcohols a entry alcohols time (h) product convn b /yield c (%) CH 2 OH CHO 99/92 5 1 98/90 5 2 CHO CH 2 OH CH 2 OH CHO 100/90 3 5 Cl Cl 99/91 5 4 MeO CH 2 OH MeO CHO Br CHO 99/84 5 5 Br CH 2 OH CHO 98/92 6 CH 2 OH 5 O 2 N CHO 5 100/81 7 O 2 N CH 2 OH MeO CHO MeO CH 2 OH 5 96/89 8 MeO MeO jiangnnan@yahoo.com
CHO 99/88 5 CH 2 OH 9 S S CHO CH 2 OH 10 97/79 5 N N CHO 5 100/89 11 Ph Ph OH CHO 12 100/77 5 OH 24 48/26 CHO 13 Ph OH Ph 24 d 94/61 CHO ( ) 6 OH 24 d ( ) 6 14 100/54 - O OH 24 15 - O OH 16 24 97/75 MeO CHO MeO CH 2 OH 4 17 12/ - CHO Ph OH Ph a Alcohol (2 mmol), 5 mol% acetamido-TEMPO, 5 mol% Cu(ClO 4 ) 2 ·6H 2 O and 10 mol% DMAP were stirred at room temperature under 1 atm oxygen for the appropriate time. b Conversion by 1 H NMR. c Isolated yield. d The reaction was carried out at 40 °C. jiangnnan@yahoo.com
Proposed Possible Mechanism Proposed Possible Mechanism RCH 2 OH H N N N N N N Cu II N N N Cu II R O NHAc I N OH 1/4 O 2 II H H NHAc O N 1/2 H 2 O N N H NHAc Cu II N 1/2 H 2 O N N O N N O H NHAc R H O N N H H III Cu I N 1/4 O 2 N N NHAc Cu II N N N NHAc OH O R OH RCHO IV H N. Jiang, A. J. Ragauskas Org. Lett. 2005 , 7 , 3689 jiangnnan@yahoo.com
Recommend
More recommend
