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entree SiliaCat

Selective Debenzylation Using SiliaCat Pd0

The selective debenzylation of aryl benzyl ethers, benzyl esters, and benzyl amines, while leaving other sensitive groups intact, can be carried out in high yield under remarkably mild conditions (namely at room temperature under 1 bar H2 in a simple hydrogen balloon, using a modest 0.5 mol % catalyst amount) using SiliaCat Pd0 (note that SiliaCat Pt0 can also be used but reaction times are longer and concentrations are higher).
Selective and smooth deprotection is critical. The commonly used method makes use of catalytic hydrogenolysis to protect benzylic groups with H2 under pressure and in the presence of a heterogeneous catalyst such as Pd/C or Raney Ni. Often, however, the deprotection reaction conditions are not compatible with other functional groups, such as nitro, unsaturated bonds, and halogen groups.
SiliaCat hydrogenation catalysts offer a number of additional advantages over traditional Pd/C. They are non pyrophoric, and have a higher density and lower catalytic consumption (<1 mol % vs 5 - 10% for Pd/C) due to fast kinetics and high turnover.

Note: refer you to our publication called “Selective Debenzylation of Benzyl Protected Groups with SiliaCat Pd0 under Mild Conditions” in ChemCatChem, 2011, 3, 1–5.

Solvent Effects

Solvent choice is critical for any debenzylation reaction. Therefore, in order to optimize the reaction conditions, 1-(benzyloxy)-4-methoxybenzene was used as our substrate of choice. A series of commonly employed solvents (THF, methanol, ethanol, ethyl acetate, and hexane) were screened under a hydrogen balloon at room temperature and at different solvent concentrations. The best results were achieved with methanol and ethanol (HPLC grade).

DebenzylationReaction

Solvent Effect
SiliaCat Pd0
(mol %)
Time
(h)
Solvent
(M)
Conversion
%
2
16
EtOH (0.1 M)
17
2
16
MeOH (0.1 M)
15
2
4
EtOH (0.07 M)
100
2
0.5
MeOH (0.07 M)
100
2
20
THF (0.07 M)
10
2
20
THF (0.07 M)
15
2
20
EtOAc (0.07 M)
20
2
20
Hexane (0.07 M)
21

 

Catalyst Concentration Effect

The molar concentration of the solvent with respect to the substrate is crucial with higher concentrations, slowing or even preventing reaction. The best results were achieved by using a methanol concentration of 0.07 M and 0.5 – 1 mol % SiliaCat Pd0, with complete conversion obtained after 1 – 2 hours.

Catalyst Concentration Effect
SiliaCat Pd0
(mol %)
Time
(h)
Solvent
(M)
Conversion
%
2
0.5
MeOH (0.07 M)
100
1
1
MeOH (0.07 M)
100
0.5
2
MeOH (0.07 M)
100

 

SiliaCat Pd0 Reusability and Leaching

Catalyst stability and reusability are crucial features of any catalyst seeking commercial applications. The SiliaCat Pd0 was thus reused six consecutive times in the O-debenzylation reaction of 1-(benzyloxy)-4-methoxybenzene under the standard mild conditions developed in our laboratory (reaction shown on previous page using 1 mol % of catalyst).
After six runs, the catalyst exhibits only a slight loss in activity compared with that of a catalyst run three times. However, the activity remained approximately constant, and it was enough to expand the reaction time to 1 h and 30 min to gain complete debenzylation of the substrate.

SiliaCat Pd0 Reusability and Leaching
Reusability
Time
(h)
Conversion
(%)
Leaching (ppm)
Pd
Si
1st
1
100
0.7
2.5
2nd
1
100
0.3
1.3
3rd
1
95
-
-
1.5
100
0.3
2.3
4th
1
95
-
-
1.5
100
0.2
1.4
5th
1
94
-
-
1.5
99
0.2
0.8
6th
1
94
-
-
1.5
100
0.1
0.5

 

SiliaCat Pd0 vs a Competitive Catalyst

Using the same reaction as that used to demonstrate the reusability of SiliaCat Pd0 in the O-debenzylation reaction of 1-(benzyloxy)-4-methoxybenzene, we also tested the commercial catalyst Pd0 EnCat, a polyurea-entrapped catalyst.

SiliaCat Pd0 vs a Competitive Catalyst
Catalyst
(mol %)
Time
(h)
Conversion
(%)
Selectivity
(%)
SiliaCat Pd0 (0.5)
1 / 2
95 / 100
- / 100
SiliaCat Pd0 (1.0)
0.5 / 1
75 / 100
- / 100
Pd0 EnCat (10)
16
100
100

 

Substrate Scope and Selectivity

SiliaCat Pd0 is an efficient catalyst for the selective debenzylation of different aryl benzyl ethers, benzyl amino-acids, and benzylprotected sugars leaving other sensitive groups intact. Refer to our publication in ChemCatChem, 2011, 3, 1–5 for more examples.

Substrate Scope & Selectivity
Substrate
SiliaCat Pd0
(mol %)
Time
(h)
Conversion
[Yield] (%)
Leaching (ppm)
Pd Si
SubstrateDebenzylation1
1
1
100 [99.7] 3.4 1.3
SubstrateDebenzylation5
1
1
100 [98.6] 1.7 5.0
SubstrateDebenzylation9
1
20
100 [98.0] 0.4 7.0

 

Conclusion of Selective Debenzylation

In conclusion, the SiliaCat Pd0 catalyst is suitable for the selective debenzylation of numerous substrates under mild conditions with a modest 1 – 2 mol % catalyst amount. Benzyl-protected sugars, amino acids, ethers, and esters are smoothly debenzylated under 0.1 MPa H2 at room temperature.

Selective Debenzylation Typical Experimental Procedure

Conventional Experimental Conditions

Reaction - Typical reactions were performed on a 1 mmol scale. The substrate was dissolved in 15 mL of MeOH or EtOH (0.07 M) and 1 or 2 mol % of the SiliaCat Pd0 catalyst was added. The mixture was degassed twice and each time replacing the vacuum by hydrogen. The reaction mixture, connected to a balloon filled with hydrogen, was stirred at room temperature until GC/MS analysis showed maximum conversion.

Work-up - Once the reaction is complete as deemed by TLC or GC-MS, the catalyst was filtered off and washed with EtOH or MeOH. The filtrate was concentrated to give a crude product. The conversion in the desired product was determined by GC/MS analysis and by 1H NMR.

Reusability - To reuse the catalyst, after completion of the reaction, remove the catalyst by filtration, rinse with MeOH/THF solvents and dry under vacuum.

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  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

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