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

fbeland@silicycle.com

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