[1758-73-2] · CH4N2O2S · Thiourea Dioxide · (MW 108.14)
(convenient and economical reducing agent for obtaining secondary alcohols from aliphatic,2 alicyclic,2 aromatic,2 heterocyclic,2 and steroidal ketones;3 efficient reducing agent for the conversion of disulfides to thiols,4 of N-tosylsulfilimines to sulfides,4 of sulfoxides to sulfides,5 and of halides and oxides of organotellurium and organoselenium to tellurides and selenides;6 synthesis of substituted imidazoles7)
Alternate Names: TUD; formamidinesulfinic acid; aminoiminomethanesulfinic acid.
Physical Data: mp 144 °C (dec).
Solubility: partially sol cold water; insol in organic solvents.
Preparative Method: prepared by oxidation of Thiourea with Hydrogen Peroxide.8
Handling, Storage, and Precautions: moisture sensitive.
A variety of ketones are reduced by TUD, in an aqueous ethanolic solution in the presence of NaOH, to the corresponding secondary alcohol in good yield. Generally, reduction of ketones requires 1-3 equiv of TUD and 2-6 equiv of NaOH; for example, dipropyl ketone gives heptan-4-ol (74%), benzophenone gives benzhydrol (100%), and 3-pyridyl phenyl ketone gives 3-pyridylphenylmethanol (100%). From the reaction mixture, almost theoretical amounts of the byproducts, sodium bisulfite and urea, are obtained.
Using TUD, in the presence of an alkoxide in alcohol, steroidal ketones are reduced to the corresponding secondary alcohols. The reduction proceeds satisfactorily in the case of 3- and 6-keto steroids.3 Steroidal diketones having a 20-oxo group do not undergo reduction with TUD. The results obtained from TUD, metal-alcohol (Bouveault-Blanc), and Lithium Aluminum Hydride reductions are compared in Table 1. With all three reducing agents, 5a-cholestan-3-one gives the equatorial isomer as the major product. With 3b-hydroxy-5a-cholestan-3-one, TUD favors a-attack to produce predominantly the axial isomer.
Disulfides and N-tosylsulfilimines are transformed into the corresponding thiols and sulfides (eq 1), respectively. For example, dibutyl disulfide is reduced to butanethiol (90%) and diphenyl disulfide to thiophenol (77%). The reactions are carried out under phase transfer conditions in the presence of a catalyst such as Tri-n-butylhexadecylphosphonium Bromide.
Sulfoxides are reduced to the corresponding sulfides by TUD in the presence of Iodine; for example, dibutyl sulfoxide gives dibutyl sulfide (89%) and diphenyl sulfoxide gives diphenyl sulfide (95%). The reaction is generally carried out by adding sulfoxides and iodine to a suspension of TUD in acetonitrile and then refluxing the mixture for a short time.
TUD reduces aryltellurium trihalides to diaryl ditellurides (eq 2) and diorganyltellurium dihalides and telluroxides to diorganyl tellurides (eq 3) in high yield. The corresponding selenium compounds are reduced similarly. Some examples are given in Table 2. The reduction is performed by premixing the substrate and 2 N NaOH at room temperature for 15 min prior to the addition of TUD in petroleum ether.
Triphenyl-b-acetylvinylphosphonium halides (X = Cl, Br) react with TUD (in DMSO) in the presence of base (Sodium Hydride) to give the imidazolylphosphonium salts in high yield (eq 4). These imidazolyl halides can be readily converted to multifunctional imidazoles with quantitative recovery of PPh3; for example, 4-methyl-(5-methylimidazolyl)triphenylphosphonium halide, on treatment with NaOMe in MeOH, affords 5-methyl-4-methoxymethylimidazole.
Marudai Balasubramanian & James G. Keay
Reilly Industries, Indianapolis, IN, USA