Silica-based reagents kit for -waves applications - SiliCycle · PDF fileSilica-based reagents...
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Silica Silica - - based reagents kit for based reagents kit for µ µ - - waves applications waves applications Michel Morin, Geneviève Gingras , and François Béland SiliCycle Inc., www.silicycle.com 1200, Ave Saint-Jean-Baptiste, suite 114, Quebec City, Quebec, Canada, G2E 5E8 [email protected] Purification using Purification using Silia Silia Bond Bond Scavengers Scavengers SiliCycle offers a wide range of scavengers to simplify your purification that can be used under µ-wave irradiation to provide excellent scavenging efficiency in a few minutes SiliaBond Scavengers Removal efficiency of Palladium Acetate Pd(OAc) 2 SiliaBond Scavenger µ-wave (%) Bulk (%) (1.0 eq) 5 min, 130 °C 5 min, rt 60 min, rt 5 min, reflux Conditions: Solution of 1 000 ppm of palladium in THF (analyzed by UV spectroscopy) SiliaBond Thiol 99.2 55.6 77.6 81.0 SiliaBond Thiourea 99.1 38.6 52.6 61.4 SiliaBond TAAcOH 97.6 20.3 36.6 74.7 Silia Silia Bond Bond Electrophile Electrophile and and Nucleophile Nucleophile Scavengers Scavengers SiliaBond Electrophile and Nucleophile Scavengers are very useful in selectively removing unreacted starting materials in the presence of the desired product Conclusion Conclusion SiliaBond products can be used with µ-wave and no degradation is observed SiliaBond Reagents can be used under µ-wave irradiation for many types of reactions A combination of SiliaBond Scavengers and µ-wave can remove metals as well as electrophiles and nucleophiles to very low levels Acknowledgements Acknowledgements The authors thank Annie Cummings and Stéphane Pelletier for their analytical support and SiliCycle would like to thank the CEM team for their outstanding support Bulk (rt, overnight) µ-wave (130°C, 5 min) Amine Acid Method 2 Method 1 Method 2 Method 1 Benzoic acid Benzylamine Amide Coupling Reactions [Yield % (Purity a %)] a : Determined by GC-FID, Yields refer to the isolated product 52.7 (99.5) 80.1 (98.1) 94.9 (95.0) 73.3 (88.0) Amide Coupling using Amide Coupling using Silia Silia Bond Bond Carbodiimide Carbodiimide SiliCycle has developed a silica-supported reagent for amide coupling, the SiliaBond Carbodiimide, that can be used with µ-wave irradiation to provide amide in high yields Si-Carbodiimide (2.0 eq) Si-Carbodiimide (3.0 eq) R 1 R 2 NH (1.0 eq) R 1 R 2 NH (1.0 eq) RCO 2 H (1.5 eq) RCO 2 H (2.0 eq) Method 1: Method 2: Reductive Reductive Amination Amination using using Silia Silia Bond Bond Cyanoborohydride Cyanoborohydride SiliCycle SiliaBond Cyanoborohydride (Si-CBH) used in µ-wave is a useful reagent for the reductive amination of carbonyl compounds Suzuki Coupling using Suzuki Coupling using Silia Silia Bond Bond Diphenylphosphine Diphenylphosphine SiliaBond Diphenylphosphine (Si-DPP) can be also used in µ-wave as linker for catalyst immobilization such as tetrakis(triphenylphosphine)palladium(0) for Suzuki couplings a : Determined by GC-FID Bulk µ-wave Solvent Ratio Carbonyl (1.0 eq) Amine (2.0 eq) (24°C, 2.5 eq Si-CBH) (120°C, 5 min) 24h 1h 1.2 eq Si-CBH > 99 > 99 > 99 87 88 75/25 Cyclohexanone 3-Phenyl-1-propylamine > 99 97 90/10 Benzaldehyde N-Benzylmethylamine 95/5 > 99 80 Benzaldehyde Piperidine Reductive Amination Reactions [% conversion a ] 57.0 (57.0) 60.0 (59.0) 2-Thiopheneboronic acid Iodoaniline Halide (1.0 eq) Boronic acid (1.1 eq) Suzuki Coupling reaction [Yield % (Purity b %)] a : Palladium immobilization ⇒ Si-DPP (1.0 eq) + Pd(PPh 3 ) 4 (0.4 eq) = Si-DPP-Pd (0.34 mmol/g) b : Determined by GC-FID, Yields refer to the isolated product (result not optimized yet) Bulk (80°C, 24h) µ-wave (120°C, 5 min) H N + N N + BH 3 CN - Si THF/AcOH (Si-CBH) H O Importance of Importance of µ µ - - wave wave Synthesis Synthesis Microwave irradiation has become more and more popular in organic synthesis because of the following benefits : Faster kinetics : only a few minutes for a reaction Higher yields and good purity Compatible with many solvents Wide variety of reactions and applications Possibility of using silica-supported reagents The The SiliCycle SiliCycle µ µ - - wave wave Kits Kits For your convenience SiliCycle, in collaboration with CEM Corporation, had developed three different silica-based kits for µ-wave applications. The available kits contains SiliaBond reagents as well as scavengers. They are described below: SiliCycle SiliaBond Reagents µ-wave kit SiliaBond Carbodiimide for amide coupling reaction SiliaBond Cyanoborohydride for reductive amination SiliaBond Diphenylphosphine for Suzuki coupling reaction SiliCycle SiliaBond Scavengers µ-wave kit Electrophile Scavengers: SiliaBond Amine and TBD Nucleophile Scavengers: SiliaBond SCX-2 Metal Scavengers: SiliaBond Thiol, Thiourea and TAAcOH SiliCycle SiliaBond Ultimate µ-wave kit Both SiliaBond Reagents and Scavengers µ-wave kits Silia Silia Bond Bond Metal Scavengers Metal Scavengers A major issue in many fields is the removal, at low level (ppb), of residual transition metals from post-reactions SiliCycle SiliaBond Metal Scavengers are used in µ-wave to provide efficient scavenging in just a few minutes + B(OH) 2 -R 1 R-X Si-DPP-Pd a (5 meq) Toluene/EtOH/H 2 O (5/1/1) Na 2 CO 3 (4.0 eq) R-R 1 Electrophiles Removal efficiency (% a ) Nucleophiles Removal efficiency (% a ) a : Determined by GC-FID, b : 80°C (results not optimized yet) Bulk (rt, 1h) µ-wave (120°C, 5min) > 98 99.0 > 98 98.0 SiliaBond SCX-2 (2.0 eq) 63.0 82.0 86.0 88.0 Bulk (rt, 1h) 50.4 80.0 91.0 97.0 µ-wave (120°C, 5min) SiliaBond TBD (2.0 eq) b SiliaBond Amine (2.0 eq) Cl O H O B OH OH S N NH 2 [CH 3 (CH 2 ) 3 ] 3 N High thermal and mechanical stability Solvent independent Suitable for use in µ-wave No swelling No static charge Characteristics of Characteristics of Silia Silia Bond Bond P P roducts roducts P Si-Diphenylphosphine N C N Si-Carbodiimide Si-Cyanoborohydride N + BH 3 CN - NH 2 Si-Amine SH Si-Thiol N N N (CH 2 CO 2 H) 2 CH 2 CO 2 H CH 2 CO 2 H Si-TAAcOH Si-SCX-2 SO 3 H Si-TBD N N N Si-Thiourea H N H N S OH Cl + N Si SiliaBond Carbodiimide C N R N R 1 O R 2 R 1 R 2 NH RCO 2 H
Transcript of Silica-based reagents kit for -waves applications - SiliCycle · PDF fileSilica-based reagents...
SilicaSilica--based reagents kit for based reagents kit for µµ--waves applicationswaves applicationsMichel Morin, Geneviève Gingras, and François Béland
SiliCycle Inc., www.silicycle.com1200, Ave Saint-Jean-Baptiste, suite 114, Quebec City, Quebec, Canada, G2E 5E8
Purification using Purification using SiliaSiliaBondBond ScavengersScavengersSiliCycle offers a wide range of scavengers to simplify your purification that can be used under µ-wave irradiation to provide excellent scavenging efficiency in a few minutes
SiliaBond Scavengers
Removal efficiency of Palladium Acetate Pd(OAc)2SiliaBond Scavenger µ-wave (%) Bulk (%)
(1.0 eq) 5 min, 130 °C 5 min, rt 60 min, rt 5 min, reflux
Conditions: Solution of 1 000 ppm of palladium in THF (analyzed by UV spectroscopy)
SiliaBond Thiol 99.2 55.6 77.6 81.0SiliaBond Thiourea 99.1 38.6 52.6 61.4SiliaBond TAAcOH 97.6 20.3 36.6 74.7
SiliaSiliaBondBond ElectrophileElectrophile and and NucleophileNucleophile ScavengersScavengersSiliaBond Electrophile and Nucleophile Scavengers are very useful in selectively removing unreacted starting materials in the presence of the desired product
ConclusionConclusionSiliaBond products can be used with µ-wave and no degradation is observedSiliaBond Reagents can be used under µ-wave irradiation for many types of reactionsA combination of SiliaBond Scavengers and µ-wave can remove metals as well as electrophiles and nucleophiles to very low levels
AcknowledgementsAcknowledgementsThe authors thank Annie Cummings and Stéphane Pelletier for their analytical support and SiliCycle would like to thank the CEM team for their outstanding support
Bulk (rt, overnight)µ-wave (130°C, 5 min)AmineAcidMethod 2Method 1Method 2Method 1
Benzoic acid Benzylamine
Amide Coupling Reactions [Yield % (Puritya %)]
a: Determined by GC-FID, Yields refer to the isolated product
52.7 (99.5) 80.1 (98.1)94.9 (95.0)73.3 (88.0)
Amide Coupling using Amide Coupling using SiliaSiliaBondBond CarbodiimideCarbodiimideSiliCycle has developed a silica-supported reagent for amide coupling, the SiliaBondCarbodiimide, that can be used with µ-wave irradiation to provide amide in high yields
Si-Carbodiimide (2.0 eq)Si-Carbodiimide (3.0 eq)
R1R2NH (1.0 eq)R1R2NH (1.0 eq)
RCO2H (1.5 eq)RCO2H (2.0 eq)
Method 1:Method 2:
Reductive Reductive AminationAmination using using SiliaSiliaBondBond CyanoborohydrideCyanoborohydrideSiliCycle SiliaBond Cyanoborohydride (Si-CBH) used in µ-wave is a useful reagent for the reductive amination of carbonyl compounds
Suzuki Coupling using Suzuki Coupling using SiliaSiliaBondBond DiphenylphosphineDiphenylphosphineSiliaBond Diphenylphosphine (Si-DPP) can be also used in µ-wave as linker for catalyst immobilization such as tetrakis(triphenylphosphine)palladium(0) for Suzuki couplings
a: Determined by GC-FID
Bulkµ-wave
SolventRatio
Carbonyl(1.0 eq)
Amine(2.0 eq)
(24°C, 2.5 eq Si-CBH)(120°C, 5 min)24h1h1.2 eq Si-CBH
> 99
> 99> 99
878875/25Cyclohexanone3-Phenyl-1-propylamine
> 999790/10BenzaldehydeN-Benzylmethylamine95/5 > 9980BenzaldehydePiperidine
Reductive Amination Reactions [% conversiona]
57.0 (57.0)60.0 (59.0)2-Thiopheneboronic acidIodoaniline
Halide(1.0 eq)
Boronic acid(1.1 eq)
Suzuki Coupling reaction [Yield % (Purityb %)]
a: Palladium immobilization ⇒ Si-DPP (1.0 eq) + Pd(PPh3)4 (0.4 eq) = Si-DPP-Pd (0.34 mmol/g)b: Determined by GC-FID, Yields refer to the isolated product (result not optimized yet)
Bulk(80°C, 24h)
µ-wave(120°C, 5 min)
HN
+N
N+ BH3CN-Si
THF/AcOH
(Si-CBH)H
O
Importance of Importance of µµ--wavewave SynthesisSynthesisMicrowave irradiation has become more and more popular in organic synthesis because of the following benefits :
Faster kinetics : only a few minutes for a reaction
Higher yields and good purity
Compatible with many solvents
Wide variety of reactions and applications
Possibility of using silica-supported reagents
The The SiliCycleSiliCycle µµ--wavewave KitsKitsFor your convenience SiliCycle, in collaboration with CEM Corporation, had developed three different silica-based kits forµ-wave applications. The available kits contains SiliaBond reagents as well as scavengers. They are described below:
SiliCycle SiliaBond Reagents µ-wave kitSiliaBond Carbodiimide for amide coupling reaction
SiliaBond Cyanoborohydride for reductive amination
SiliaBond Diphenylphosphine for Suzuki coupling reaction
SiliCycle SiliaBond Scavengers µ-wave kitElectrophile Scavengers: SiliaBond Amine and TBD
Nucleophile Scavengers: SiliaBond SCX-2
Metal Scavengers: SiliaBond Thiol, Thiourea and TAAcOH
SiliCycle SiliaBond Ultimate µ-wave kitBoth SiliaBond Reagents and Scavengers µ-wave kits
SiliaSiliaBondBond Metal ScavengersMetal ScavengersA major issue in many fields is the removal, at low level (ppb), of residual transition metals from post-reactions
SiliCycle SiliaBond Metal Scavengers are used in µ-wave to provide efficient scavenging in just a few minutes
+ B(OH)2-R1R-X
Si-DPP-Pda (5 meq)
Toluene/EtOH/H2O (5/1/1)Na2CO3 (4.0 eq)
R-R1
Electrophiles Removal efficiency (%a)
Nucleophiles Removal efficiency (%a)
a: Determined by GC-FID, b: 80°C (results not optimized yet)Bulk (rt, 1h)µ-wave (120°C, 5min)
> 9899.0> 9898.0
SiliaBond SCX-2 (2.0 eq)
63.082.086.088.0Bulk (rt, 1h)50.480.091.097.0µ-wave (120°C, 5min)
SiliaBond TBD (2.0 eq)bSiliaBond Amine (2.0 eq)
Cl
O
H
O
BOH
OH
S
NNH2[CH3(CH2)3]3N
High thermal and mechanical stability
Solvent independentSuitable for use in µ-wave
No swellingNo static charge
Characteristics of Characteristics of SiliaSiliaBondBond PProductsroducts
PSi-Diphenylphosphine
NCN
Si-Carbodiimide
Si-Cyanoborohydride
N+BH3CN- NH2 Si-Amine
SH Si-Thiol
NN
N(CH2CO2H)2
CH2CO2H
CH2CO2H Si-TAAcOH
Si-SCX-2SO3H
Si-TBDN
NN
Si-ThioureaHN
HN
S
OH
Cl
+
NSi
SiliaBond Carbodiimide
C N
R NR1
O
R2
R1R2NHRCO2H
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