Schreiner’s Thiourea Catalyst

Technical Specifications

Product Description & Scientific Applications

Schreiner's Thiourea Catalyst (N,N′-bis[3,5-bis(trifluoromethyl)phenyl]thiourea) is an achiral hydrogen-bond-donor organocatalyst. It is a bench-stable solid, soluble in methanol, ethanol, dichloromethane, ethyl acetate, acetonitrile, toluene, and DMSO, and insoluble in water and hexane. Being achiral, it accelerates and activates reactions rather than inducing enantioselectivity; the 3,5-bis(trifluoromethyl)phenyl motif it introduced is now the standard building block of chiral (thio)urea catalysts.

Mechanistic basis. The two thiourea N–H bonds donate a pair of hydrogen bonds simultaneously (bidentate donation) to a Lewis-basic acceptor — a carbonyl, imine, nitro group, or nitrone — activating the electrophile and stabilising the negative charge (oxyanion) that develops in the transition state; the catalyst thereby behaves like a Lewis acid without a metal. Two structural features make it effective. The electron-withdrawing 3,5-bis(trifluoromethyl)phenyl groups raise the acidity of the N–H bonds — the pKa in DMSO is about 8.5, the most acidic among common thiourea organocatalysts — strengthening the hydrogen bonds. An intramolecular contact between the aryl ortho-hydrogens and the thiocarbonyl sulfur rigidifies the molecule, lowering the entropic penalty of binding a substrate. Thiourea is preferred over the urea analogue for its greater solubility and weaker self-association.

Applications and Reactions

• Cycloadditions. Activates dienophiles such as N-acyloxazolidinones for Diels–Alder reactions and 1,3-dipolar cycloadditions, with catalytic activity retained in water.
• Acetalization and hydroxyl protection. Catalyses acid-free acetalization of aldehydes and ketones and tetrahydropyranylation of alcohols and phenols, tolerating acid-sensitive substrates (aldol products, silyl ethers, cyanohydrins); the pyranylation reaches turnover numbers up to 100,000 and frequencies up to 5700 h⁻¹ at loadings as low as 0.001 mol%, operating by hydrogen-bond-assisted heterolysis and oxyanion-hole stabilisation.
• Friedel–Crafts alkylation. Promotes conjugate addition of electron-rich arenes and heteroarenes (anilines, pyrroles, indoles) to nitroolefins, forming C–C bonds under mild, metal-free conditions.
• Cyanation and Strecker reactions. Activates aldimines and nitrones toward cyanide sources (TMSCN, acetyl cyanide), giving α-amino nitriles and N-hydroxylamines, including three-component acyl-Strecker variants.
• Biomimetic reduction. With a Hantzsch ester as hydride source, catalyses transfer hydrogenation of aldimines to secondary amines and reduction of conjugated nitroolefins to nitroalkanes.
• Sulfide oxidation. Activates tert-butyl hydroperoxide for chemoselective oxidation of sulfides to sulfoxides.
• Epoxide ring-opening. Catalyses opening of epoxides by nucleophiles, with the largest rate accelerations in water — up to 200-fold faster than in dichloromethane.
• Alternative activation mode. Beyond hydrogen-bond donation, the thiocarbonyl sulfur can act as a Lewis base — for instance in the N-bromosuccinimide-mediated oxidation of secondary alcohols to ketones.

Shipping Destinations

• EU & UK: Priority delivery, 2–5 business days.
• United States (DDP): 3–7 business days, duties and taxes prepaid.
• EFTA Countries (DDP): 3–7 business days, duties and taxes prepaid.
• Worldwide: 7–14 business days, selected locations.