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Biotage® PS-Isocyanate

Powerful Scavenger of Nucleophiles

MP-isocyanate

Biotage® PS-Isocyanate can readily scavenge excess nucleophiles, which are often used to drive reactions to completion. The reaction of nucleophiles with the isocyanate moiety occurs without liberation of small molecule by-products.

CONSUMABLES

Part No. Description Product type Pack Size Price
800260 PS-Isocyanate, 10 g Consumables 1 Log in for price
800261 PS-Isocyanate, 25 g Consumables 1 Log in for price
800262 PS-Isocyanate, 100 g Consumables 1 Log in for price
800311 PS-Isocyanate, 1 kg Consumables 1 Log in for price
800495 PS-Isocyanate, 3 g Consumables 1 Log in for price

Committed to preserving our shared environment – further details available on request.

Can be used in processes in compliance with cGMP standards.

Manufacture of consumables is accredited by the world renowned British Standards Institute.

Flexible supply chains, back up manufacturing and warehousing ensures supply risk reduction

Can be used in processes in compliance with GLP standards.

Products which are scaleable from lab or development to process scale.

Long to indefinite product shelf life, reduced process risk.

Supports pharma guidelines for reducing elemental impurities in APIs.

Further extractable information provided on request.

Raw materials certified free of materials of human or animal origin.

Chemical substances used in our manufacturing process do not require registration.

Able to withstand mechanical stirring and heating under normal reaction conditions.

Download the product note.

 

Background

Biotage® PS-Isocyanate is a 1% cross-linked poly(styrene-co-divinylbenzene) which has pendent benzylisocyanate functionality. The resin can readily scavenge excess nucleophiles, which are often used to drive reactions to completion. This facilitates workup and purification. The reaction of nucleophiles with the isocyanate moiety occurs without liberation of small molecule by-products.
Removal of nucleophiles from solution generally requires 2–3 equivalents of PS-Isocyanate depending on substrate reactivity (Scheme 1).

Comparative scavenging of amines (0.2–0.05 M) of varying reactivity was tested as a function of time and temperature (Table 1). Typical aliphatic amines are completely sequestered by three equivalents of PS-Isocyanate within 1 h. Three equivalents of PS-Isocyanate sequestered 100% aniline at room temperature over 16 h. A less reactive aromatic amine, 2-aminobenzophenone, was not completely sequestered even at elevated temperatures. The use of DIEA as a catalyst did not improve the scavenging efficiency of PS-Isocyanate towards aromatic amines. Alcohols were not reactive towards PS-Isocyanate at room temperature, suggesting that aliphatic amines can be selectively sequestered in the presence of alcohol functionality. More nucleophilic alcohols may be removed at elevated temperatures.

 

Nucleophile
Scavenged

PS-Isocyanate (equivalent)

Temp (˚C)

% Scavenged

1 h

16 h

Piperidine

3.0

20

100

-

Benzyl amine

3.0

20

100

-

Aniline

3.0

20

-

100

Aniline

3.0

60a

92

100

2-Aminobenzophenone

3.0

60a

-

81

 

Upon completion of the scavenging, the product is removed from the resin by washing with a suitable solvent. Suitable solvents include those which dissolve the product and swell polystyrene but are not nucleophilic enough to react with the resin. DCM, dichloroethane, THF, and toluene are all good choices with DCM being preferred.

Representative Procedures

Amide Formation

4-chlorobenzoyl chloride was allowed to react for 1 h with 1.5 equivalent of benzylamine in DCM with 3 equivalents of base. Excess benzylamine was scavenged by adding PS-Isocyanate resin (3 equivalents relative to excess amine). Beads were removed by filtration, washed twice with DCM and the combined filtrate was concentrated to afford the benzyl 4-chlorobenzamide as the sole product in 87% yield.

Reductive Alkylation of Secondary Amines

A THF solution (0.5 M) of N-methylpiperazine (1.2 mL, 0.60 mmol) was added to a THF solution (0.5 M) of cyclohexanecarboxaldehyde (1.0 mL, 0.50 mmol). MP-Triacetoxyborohydride (2.0 mmol/g, 0.625 g, 1.25 mmol) was then added and the mixture was agitated for 16 h at room temperature. When the reaction was complete, PS-Isocyanate (0.4 g, 0.5 mmol) and THF (2 mL) were added and the mixture was further agitated for 6 h. The resin was filtered and washed with THF (4 mL x 2). The combined solution was concentrated to afford the tertiary amine product in 92% yield and 99% purity. The tertiary amine was characterized by gas chromatography and 1H NMR.