Environmentally Friendly Routes for the Selective Oxidation of Alcohols Setrak K. Tanielyan and Robert L. Augustine

Transcription

1 Environmentally Friendly Routes for the Selective xidation of Alcohols Setrak K. Tanielyan and Robert L. Augustine Center for Applied Catalysis Department of Chemistry and Biochemistry Seton all University South range, NJ USA

2 Aspartame to Neotame Me N N 3 2, Pd/C Me N N 2 Aspartame 170 x 2% Sucrose Neotame 11,000 x 2% Sucrose

3 Need for Green oxidation methods Twelve principles of Green Chemistry 1. Prevention of waste rather than treatment 2. Atom Economy 3. Less azardous Synthesis 4. Safe Chemicals 5. Safer solvents and auxiliaries or none at all 6. Energy Efficient Design 7. Use of Renewable Feedstock 8. Reduce Derivatives 9. Catalysis as selective as possible 10. Design for degradation 11. Real Time Analysis for Pollution Prevention 12. Inherently Safer Chemistry for Accident Prevention Anastas and Warner. Green Chemistry, Theory and Practice, xford, 1998.

4 Alternate oxidation processes conforming to 4 principles NaCl TEMP Based Anelli Protocol US Pat 6,825,384

5 Route selection: Anelli method Me + NaCl N (1mol%) KBr (10mol%) C 2 Cl 2, 0 C, p NaCl + 2 The oxidation takes place in a two-phase system. rganic phase: 5% R Solution in C 2 Cl 2 Me-TEMP catalyst (1 mol%) Aqueous phase: NaC 3 buffer at 8.6 (0.7M) KBr dissolved in the buffer Additional requirements: Monitoring and control of p Control of the Temperature (-2-0 C) Efficient and controlled stirring Metered addition of the NaCl solution (25% excess) Deficiencies: Low Substrate : cat ratio (100) Large volume MC Solvent Excessive Volume buffer used Need of Br - based co-catalyst Anelli, Biffi, Montanari. J.rg.Chem. 1989, 54, 2559

6 Reaction Efficiency Component 8 Mmol Scale 100kg Scale Target Priority G (cc) kg (L) kg (L) 3,3 DMBAL Me -TEMP (At ~$300kg) <0.5 1 KBr None 4 NaC NaCl solution (515) C 2 Cl 2 (20) (2447) None 2 Buffer Solution (22) (2692) None 3

7 Fine Tuning the xidation Reaction Four Stage Approach Stage 1 - Screening of all available TEMP derivatives as catalysts Stage 2 Selecting environmentally friendly solvents and volume reduction Stage 3 Screening a large number of metal salts as a potential co-catalyst Stage 4 - Determining conditions for minimizing the level of the by-products Stage 1 Me NCC 3 N(C 3 ) 2 N N N N N (C2 ) 6 N N N N N N(tert-C 8 ) 5 Me-TMP ~ = > > >> > AA-TMP TMP P-TMP -TMP DMA-TMP

8 Stage 1: Catalyst optimization Conditions: T= 0 C, [DMBAL]=8mmol, [NaCl]=8.92mmol, TEMP : Br - =1:1 p=8.6 (NaC 3 20cc), Toluene 20cc Yield of 3,3-DMBALD, % % 0.50% S/C=100 TF= % S/C=800 TF=6.7 min % 0.50% S/C=100 TF= % S/C=800 TF=5.3 min % 0.05% 0.25% S/C=400 TF=2.3 min -1 Me-TEMP TEMP P-TEMP Time, min Time, min Time, min Result: Eight fold reduction in the catalyst concentration only extends the reaction time without changes in the product selectivity.

9 Stage 2: Solvent selection Large number of solvents screened. igh rates recorded in Acetone and Toluene Yield 3,3 - DMBALD, % Acetone Problem with these two candidates can t be used. The Toluene and DMBALD have close b.p. C 2 Cl 2 Toluene 1- MeAc 2 - TF 4 - DEE Time, min Conditions: T= 0 C, [DMBAL]=8mmol, [NaCl]=9.2mmol, p=8.6, [Me-TEMP] = 1%mol, [KBr]=1%mol, Solvent 20cc Pentane Traces of Acetone in the product will interfere in the next step of the reductive alkylation of ASP. Then, if you really don t know which way to go, try to eliminate the solvent. Concentration 3,3-DMBALD, mol/l Post Addition Time, min [C]=100% Y = 91.6% [C]=75% Y = 91.8% [C]=50% Y = 90.6% [C]=25% Y = 88.8% [C]=12.5% Y = 82.2%

10 Stage 3: Finding a co-catalyst Screening of Large number soluble oxymetal ions of Mo 6+, W 6+, V 5+, Ti 4+, Zr 4+, known to act via peroxometal and/or oxometal mechanism. Finding no reasonable alternative to the existing KBr based protocol. Decided to at least improve the buffer system. Results better then expected.

11 Stage 3: Finding a co-catalyst # Catalyst Buffer composition, % mol GC Yield, % Comments # M-TMP KBr Na 2 B None ptimized reference None 94 95?! None None 0.85 None Need of Buffer None Less M-TEMP None None New co-catalyst? Na 2 B 4 7 most likely serves as a co-catalyst, effectively replacing the KBr Shows superior performance and better selectivity compared to standard KBr It allows more efficient use of the Me-TEMP catalyst It s place in the overall red-ox cycle yet to be determined

12 Stage 4: Minimizing the level of by-products First to identify the by-products detected during the oxidation of 3,3-DMA. NaCl Cl 3,3-DMBACID At p < 9.0 Cl -C 2 R 6 R 6 -Ester C 6 -C 6 emi Acetal Cl R 5 -Cloride At p >9

13 Stage 4: Minimizing the level of by-products Reaction parameters controlling the level of the detected by-products. 6.0 [TEMP]=0.17, p=8.6 [Na 2 B 4 7 ]=0.44, StR 1200 [Na 2 B 4 7 ]=0.44, p= Yield Yield Yield 90.0 [By-Product], % wt C5-Cl Ester emi Acetal C5-Cl Ester emi Acetal Acid C5-Cl Ester Acid emi Acetal Yield Crude Aldehyde, % Acid [Na 2 B 4 7 ], mol % Reaction p Stirring Rate, RPM igh Reaction Selectivity [Na 2 B 4 7 ], p, Stirring Rate

14 End Results DMBAL: Me-TEMP = 280, DMBAL : Borax = 200 NaCl : DMBAL = 1.2, T = 0 C, NaC 3 buffer, p = 8.9, 2x volume of DMBAL, Rapid Stirring Volume Reactants, L % of V t 37.5% of V t R Buffer Solvent NaCl 0 At Start Final riginal Procedure With Solvent At Start Final Target Procedure Without Solvent

15 Scope of Application xidation of model alcohols in presence of TEMP derivatives (New protocol) Alcohol Product X-TEMP Yield, % 1. eptan-1-ol Me-TEMP eptan-1-ol Me-TEMP exan-1-ol Me-TEMP Benzyl alcohol Me-TEMP Methylcyclohexanol Me-TEMP Methyl-2-pentanol Me-TEMP ,3-Dimethylbutanol Me-TEMP ,3-Dimethylbutanol TEMP ,3-Dimethylbutanol AA-TEMP 88 in 2 min PAT Conditions: T= 0 C, [DMBAL]=117mmol, NaCl=123mmol, p=8.6, [X-TEMP] = 0.2 %mol, [Na 2 B 4 7 ]=0.65%mol, Solvent 20cc (for 1-6) and no solvent (for 7-9)

16 Alternate xidation Routes 2 TEMP Based Catalyst System US Pat 7,030,279

17 Deficiencies and Targets Deficiencies of existing aerobic oxidation procedures Low substrate:catalyst ratio (S:C) currently, less than 100 Large volume of solvent substrate concentration of 5% v/v or less Precious or transition metals as co-catalysts Use of exotic ligands and halogenated solvents Targets S:C ratio 100 or more Substrate concentration 60% v/v using environmentally friendly solvents Transition metal free catalyst system Low temperature / low pressure protocol

18 Initial Screening Screening of 4 representative 5% Ru/Carbon supported catalysts for 1-exanol (in Ac) Finding reaction initiated after long induction periods Attempts to eliminate the induction period. The results better then expected. # Catalyst Composition, % mol Efficiency, % Comments # 5%Ru/C Me-TEMP Mg(N 3 ) 2 NBS Rate Cnv Sel None None Long induction (4h) None None Need all 3 components Re-used Ru/C 6 None No need for Ru Mg(N 3 ) 2 + NBS serve as a co-catalyst, effectively replacing supported Ru Mg(N 3 ) 2 + NBS show superior performance and better selectivity It allows more efficient use of the TEMP catalyst It s place in the overall redox cycle yet to be determined

19 TEMP derivative 2 Uptake rate, mmol/min 1-exanol = 16mmol (2cc), Ac = 10cc, T=46 C, p 2 =15psi, Mg(N 3 ) 2 = 1.2mmol, NBS = mmol Rate 0.30 Cnv Cnv Cnv Sel Sel Sel (a) (b) (c) Rate Rate Me-TEMP TEMP AA-TEMP S/C=13 S/C=13 S/C= [Me-TEMP], mmol [TEMP], mmol [AA-TEMP], mmol Conversion (Selectivity), % For all TEMP s, the selectivity deteriorates at high TEMP concentrations (plot a, b,c ) AA-TEMP is two times more efficient than TEMP & Me-TEMP AA-TEMP and TEMP are both more resilient than Me-TEMP 4-ydroxy-TEMP: significantly lower Cnv, Sel & Rate

20 Pressure and Temperature Effect 1-exanol = 16mmol (2cc), Ac= 10cc, AA-TEMP = 0.64mmol, Mg(N 3 ) 2 = 1.2mmol, NBS = 0.048mmol Uptake rate, mmol/min C 40C 37C 34C Conversion at 30min, % C 40C 37C 34C Selectivity at 30min, % C 37C 40C 43C Reaction pressure, psi Reaction pressure, psi Reaction pressure, psi The reaction is first order in oxygen partial pressure At 43 C and 16mmol reaction scale, a full conversion is achieved over 20min with a TF of 1.25 min -1 The aldehyde selectivity could be controlled by monitoring the 2 uptake

21 Reduction of Ac Volume at igh S:C Gradual increase of the alcohol concentration keeping the total volume constant 1-exanol = variable, Ac = variable, Reaction volume = 12cc, T=48 C, p=15psi, AA-TEMP = 0.48mmol, Mg(N 3 ) 2 = 0.48mmol, NBS = mmol R=8mL 64mmol 66.7% Vol xygen Uptake, mmol R=2mL 16mmol 16.6% Vol C=100% R=4mL 32mmol 33.3% Vol Cnv=95.5% R=6mL 48mmol 50% Vol A Cnv= 57.6% B Cnv= 7.4% Attempts to activate composition A and B Time, min Severe inhibition at substrate concentrations higher than 30% v/v Apparently the substrate deactivates one of the components of the catalyst.

22 Reduction of Ac Volume xygen Uptake, mmol xygen Uptake, mmol xygen Uptake, mmol Theoretical Uptake Cnv= 75-78% Theoretical Uptake Cnv= 73-77% Theoretical Uptake Sub/Cat=83 1 [AA-TEMP] 0.58 mmol 0.53 mmol 0.48 mmol [Mg(N3)2] 0.58 mmol 0.53 mmol 0.48 mmol mmol [NBS] mmol Cnv= 99% Sel = 95% Variation in [AA-TEMP] (plot 1) and [Mg(N 3 ) 2 ] (plot 2) did not change the activity of the catalyst composition Surprisingly, increasing [NBS] to 0.5 mol% led to a smooth oxidation, resulting in complete conversion and 95% aldehyde selectivity (plot 3) At a substrate to catalyst ratio of 83 and [NBS ] = 0.19mmol, the TF was 1.34 min -1 1-exanol = 40mmol (5cc), Ac = 7cc, reaction volume 12cc, 42 % v/v in Ac, T=48 C, p 2 =15psi, AA TEMP = 0.48mmol, Mg(N 3 ) 2 = 0.48mmol, NBS = variable, S/C = 83 Time (min)

23 Scope & Limitations igh reaction rates & selectivity C-6 Low reaction rates high selectivity C-7 C-8 C-11 No reactivity N

24 Alternate xidation Routes Cu Catalyst Vapor Phase Dehydrogenation Know ow

25 Dehydrogenation By-Products C 3 C 2 C 3 C 3 C 3 C 2 C 2 C 3 C 3 Acid Ether C 3 C 3 C 3 C 2 C 3 Ester

26 Long-Term Vapor Phase Reaction Data

27 Co-Workers Center for Applied Catalysis Clementina Reyes Nagendranath Mahata Gabriela Alvez Norman Marin The NutraSweet Corporation Indra Prakash Kenneth Furlong enley Jackson Robert Scherm Degussa, BU Building Blocks Michael Korell (Parsippany, NJ) liver Meyers (Marl, Germany)