Follow SiliCycle on Facebook Follow SiliCycle on Twitter Follow SiliCycle on LinkedIn Watch our videos on Youtube

entree SiliaCat

Oxidation Using SiliaCat TEMPO

Aldehydes and ketones, either as starting materials, synthetic intermediates, or final products, are of great interest in synthetic chemistry. Such carbonyl-containing products can lead to carbon–carbon (i.e. Wittig, Aldol, alkylation) or carbon–nitrogen bond formation. Over the years, chemists have discovered various oxidizing agents such as pyridinium chlorochromate (PCC), MnO2, Dess-Martin periodinane, or Swern oxidation conditions. Although all these methods lead to the aldehyde (limited oxidation of the aldehyde to the carboxylic acid), they have drawbacks such as the hazards and toxicity associated with
residual metal contamination.
Development of environmentally friendly methods such as selective catalytic oxidation of alcohol substrates to aldehydes and ketones can have significant impact on modern methods of chemical synthesis. SiliaCat TEMPO is the oxidation solution of choice.

 

CatalyticOxidationBenzaldehydeReaction

 

Catalytic Performance and Leaching

SiliaCat TEMPO was investigated in the Montanari-Anelli conditions. The catalytic cycle involves regeneration of the oxidative species with NaOCl (commercially available bleach) in presence of KBr as co-catalyst to form the stronger anion OBr-.
Unless otherwise stated, the reaction shown below was used for the demonstration.

CatalyticOxidationBenzaldehydeLeachingReusability

Catalyst Concentration Effect
SiliaCat Tempo
(mol %)
Time
(h)
Solvent
(M)
Ton
Si Leaching
(ppm)
0.1
1
95
950
-
0.01
2
83
8,300
3
0.01
3
95
9,500
1.6
0.01
4
97
9,650
1.5
0.02
2
96
4,800
-
0.02
3
100
5,000
2

SiliaCat TEMPO can be used with as low as 0.01 mol % quantity to provide the desired aldehyde in short reaction times. ICP analysis confirms that the material is leach-resistant ([Si] ≤ 3 ppm).

 

SiliaCat TEMPO Reusability

Minimal leaching and the robustness of SiliaCat TEMPO’s organoceramic matrix allow it to be reused several times for further uses.

SiliaCat TEMPO Reusability
Reusability
Time
(min)
Conversion
(%)
1st
30
100
2nd
30
100
...
...
...
8th
30 / 60
95 / 100
9th
30 / 60
97 / 100
10th
30 / 60
90 / 100

aSiliaCat TEMPO is recycled by post-reaction filtration, DCM washes and air drying.

 

Influence of Co-Catalyst KBr and Temperature

SiliCycle investigated wether it was necessary to use a co-catalyst (KBr) for the reaction to proceed effectively. As shown in the table, although KBr is not required for the reaction, it does have a significant impact on the kinetics. The reaction can still proceed to completion without KBr but requires longer time and/or more SiliaCat TEMPO. It was also demonstrated that the reaction can be carried out at room temperature without KBr.

Influence of KBr and Temperature
SiliaCat
(mol %)
Kbr
(eq.)
Temp.
(°C)
Time
(min)
Conversion
(%)
0.1
0.1
0
60
95
0.1
0
0
60
80
0.1
0
0
210
100
0.2
0
0
105
96
0.2
0
22
60
76
0.2
0
22
90
87

 

Influence of Solvents, pH and NaOCl

As shown on the right, the reaction can be carried out at pH 9.0 or at pH 7.5 in DCM with high conversion yields. The catalytic conditions are selective towards the aldehyde, rather than the carboxylic acid, even with 10 equiv of NaOCl. At pH 7 in water, the reaction is slower, but this can be overcome by using more NaOCl(aq). At pH 9, the conversion is high, but too much bleach and the long reaction time in the aqueous media will lead to the corresponding carboxylic acid. The reaction can also be pursued in other organic solvents.

CatalyticOxidationBenzaldehydeInfluence

Influence of Solvent, pH and NaOCl(aq)
SiliaCat
(mol %)
NaOCl(aq)
(eq.)
Solvent
pH
Time
(min)
Conversion
(%)
0.2
2.50
DCM
9.0
60
98
0.2
10.00
DCM
9.0
90
98
0.2
1.25
DCM
7.5
60 / 90
83 / 86
0.2
2.50
DCM
7.5
60 / 90
94 / 98
0.2
1.25
H2O
7.5
60 / 90
57 / 65
0.2
2.50
H2O
7.5
60 / 90
87 / 88
0.7
1.20
H2O
9.0
60 / 150
83 / 89
0.8
5.00
H2O
9.0
60 / 18 h
60 (19)/ 7 (89)1
0.2
1.25
EtOAc
9.0
60 / 90
95 / 96
1 In parenthesis = conversion to carboxylic acid.

 

SiliaCat TEMPO vs Homogeneous TEMPOs

Comparative analysis versus homogeneous TEMPOs demonstrates the SiliaCat TEMPO to be comparable or better at neutral pH and significantly superior in basic conditions.

CatalyticOxidationBenzaldehydeHomogeneous

SiliaCat TEMPO vs Homogeneous TEMPOs
pH
SiliaCat Tempo
4-MeO-TEMPO
4-Oxo-TEMPO
7.5
91
99
45
9.0
98
55 (40)1
73
1 In parenthesis = conversion to carboxylic acid.

 

Substrate Scope with SiliaCat Tempo

SiliaCat Tempo is efficient with different substrates and can be used with phase a transfer agents such as Aliquat 336. When an electron-rich benzylic alcohol cannot be oxidized successfully with NaOCl, conditions involving I2 in toluene, at room temperature, will yield the desired product.

CatalyticOxidationBenzaldehydeSubstrateScope

Influence of Solvent, pH and NaOCl(aq)
Substrate
(R)
Catalyst
(mol %)
Time
(min)
Conversion
(%)
3-NO2
0.4
90
100
4-NO2
0.4
90
98
4-OCH3
0.4
90
36
4-OCH3
0.4 (0.05 eq. Aliquat 336)
60
79
4-CL
0.4
90
95
3-phenyl-
1-propanol
0.4
60
97
1-phenyl-
3-propanol
0.4
180
95
4-OCH3
8.2
16 h
99
3-OCH3
7.8
16 h
96
Piperonal
10.0
20 h
100
1Exp. Cond.: I2 (1.8 eq.), NaHCO3(aq), pH 8, toluene, 22°C.

 

Conclusion of Oxidation

In conclusion, the SiliaCat TEMPO is an effective oxidizing catalyst presenting unique advantages such as high activity, robustness, leach-proof properties and selectivity toward the oxidation of alcohols into aldehydes and ketones, both very valuable products in organic chemistry.

 

Oxidation Typical Experimental Procedure

 

Oxidation of Alcohols or Aldehydes to Carboxylic Acid

Note: changing the solvent to water, increasing temperature and the amount of bleach will all favor the acid formation.

Conventional Experimental Conditions

Reaction - Under mechanical agitation, a 0.4M solution of alcohol in water and a 0.5 M aqueous solution of KBr were cooled at 0°C in an ice bath. The desired amount of SiliaCat TEMPO was added, followed by an aqueous solution of NaOCl (from 10-13% bleach) buffered at pH 9 (using NaHCO3) or pH 6.7 (using NaH2PO4/Na2HPO4). NaOCl was added slowly over a 10 minute period as the reaction is exothermic. The mixture was warmed to room temperature (20°C) and stirred between 1,300-1,500 rpm. The temperature can be increased to 35°C if necessary.

Work-up - Once the reaction was complete (determined by TLC or GC-MS), the catalyst was filtered at room temperature, and the pH was adjusted to 12 with aqueous NaOH (2N). The aqueous phase was separated, acidified with HCl 6N and extracted with CH2Cl2. The organic phase was dried over MgSO4 and evaporated. The residue was purified by crystallization or column chromatography on silica gel.

• 1.2 - 5 eq. of NaOCl(aq) (typically start with 3 eq. and, if necessary, add another 2 eq. of NaOCl via an addition funnel after all of alcohol is consumed)
• 0.1 eq. of potassium bromide (KBr) (prepared as a 0.5 M solution)
• pH 9 is achieved using a NaHCO3 buffer or a pH of 6.7 is achieved using a sodium phosphate buffer (1:1 mixture of 0.67 M NaH2PO4 and 0.67 M Na2HPO4)
• 0.01 - 1 mol % of SiliaCat TEMPO (typically 1 mol %)
• The best solvents are H2O, ACN/H2O or DCM/H2O, typically at 0.4 M (molar concentration with respect to the substrate)

 

Oxidation of Primary or Secondary Alcohols

 

Under Montanari-Anelli Conditions (using NaOCl)

Conventional Experimental Conditions

Reaction - Under mechanical agitation, a 0.4M solution of the alcohol in dichloromethane is mixed with a 0.5M aqueous solution of KBr and cooled at 0°C in an ice bath. The desired amount of SiliaCat TEMPO is then added, followed by an aqueous solution of NaOCl (from commercially available 10-13% bleach), then the solution is buffered at pH 9 (using NaHCO3). NaOCl solution is added slowly over a 10 minute period as the reaction is exothermic. The mixture is then stirred between 1,300-1,500 rpm.

Work-up - Once the reaction is complete (determined by TLC or GC-MS), the catalyst is filtered at room temperature, and the organic phase is dried over MgSO4 and evaporated. Crude mixture is purified using flash chromatography, if needed.

 

Under Miller Conditions (using I2 co-catalyst)

Conventional Experimental Conditions

Reaction - Under mechanical agitation, a 0.4M solution of alcohol in toluene is mixed at room temperature (20°C) with a 0.3 M aqueous solution of NaHCO3. Solid iodine is then added in one portion to the mixture, followed by the desired amount of SiliaCat TEMPO.

Work-up - Once the reaction is complete (determined by TLC or GC-MS), the catalyst is filtered at room temperature. The mixture should then be cooled to 5°C, diluted with ethyl acetate, and quenched with a 0.8M aqueous solution of Na2SO3. The uncolored organic phase is then washed with a saturated aqueous solution of NaHCO3 followed by brine and dried over MgSO4. After filtration and evaporation of the solvents, the crude mixture can be purified using flash chromatography.

• For Montanari-Anelli conditions: 1.2 - 5 eq. of NaOCl(aq) (typically 2.5 eq.) and 0.1 eq. of KBr (prepared as a 0.5 M solution)
• For Miller conditions: 1.8 eq. of solid iodine (I2)
• 0.001 - 1 mol % of SiliaCat TEMPO (typically 1 mol %)
• The best solvents are DCM, EtOAc or ACN/H2O (HPLC grade), typically at 0.4 M (molar concentration is with respect to the substrate)

 

SiliCycle Publications


SiliaCat TEMPO Oxydation

  • Topics in Catalysis, 2010, 53, 1110-1113
  • Organic Process Research & Development, 2010, 14, 245–251
  • Chemistry Today, 2009, 27, 13-16
  • Organic Process Research and Developement, 2007, 11, 766-768
Hydrogenation of nitroarenes with SiliaCat Pt0
  • Advanced Synthesis & Catalysis, 2011, 353, 1306–1316
  • Catal. Sci. Technol., 2011, Advance Article, DOI: 10.1039/C1CY00097G
Suzuki coupling with SiliaCat
  • Catal. Sci. Technol., 2011, Advance Article, DOI: 10.1039/C1CY00119A
  • Topics in Catalysis, 2010, 53, 1059-1062
Selective debenzylation with SiliaCat Pd0
  • ChemCatChem, 2011, 3, 1146-1150

 

5 Item(s)

Set Descending Direction
per page

List  Grid 

  1. SiliaCat DPP-Pd heterogeneous catalyst

    SiliaCat® Heterogeneous Catalysts DPP-Pd

    Typical Applications: Suzuki, Heck, Sonogashira, Kumada, Stille and Buchwald amination
  2. SiliaCat® Heterogeneous Catalysts TEMPO

    SiliaCat® Heterogeneous Catalysts TEMPO

    Typical Applications: Oxidation of alcohols or Aldehydes
  3. SiliaCat® Heterogeneous Catalysts Pd0

    SiliaCat® Heterogeneous Catalysts Pd0

    Typical Applications: Suzuki, Heck Sonogashira, Kumada, Stille, Selective debenzylation, Selective hydrogenation
  4. SiliaCat® Heterogeneous Catalysts Pt0

    SiliaCat® Heterogeneous Catalysts Pt0

    Typical Applications: Selective reduction of nitroarenes, Hydrosilylation
  5. SiliaCat® complete heterogeneous catalysts kit: SiliaCat DPP-Pd, SiliaCat Pd0, SiliaCat Pt0 and SiliaCat TEMPO

    SiliaCat® complete heterogeneous catalysts kit

    Containing SiliaCat DPP-Pd, SiliaCat Pd0, SiliaCat Pt0 and SiliaCat TEMPO

5 Item(s)

Set Descending Direction
per page

List  Grid