[54974-07-1] · C8H4ClNO2S · Phthalimidosulfenyl Chloride · (MW 213.65)
(reacts as a pseudohalogen;1 synthetic equivalent of inaccessible sulfenyl chlorides;2-4 adds across double and triple bonds;2,3,5 reagent for the formation of episulfides;6 reacts with ketones to give b-keto sulfides7)
Alternate Names: phthalimide-N-sulfenyl chloride; 1,3-dihydro-1,3-dioxo-2H-isoindole-2-sulfenyl chloride; N-(chlorothio)phthalimide.
Physical Data: mp 115-117 °C.
Solubility: sol chlorobenzene, benzene, CH2Cl2, MeOH; insol pentane.
Form Supplied in: yellow crystals; not commercially available.
Preparative Method: prepared by treatment of potassium phthalimide with S2Cl2 to form the disulfide which is then cleaved with chlorine in warm chloroform.1
Purification: recrystallization from methanol.
Handling, Storage, and Precautions: can be stored at 0 °C for several months.
Phthalimidosulfenyl chloride adds to unsymmetrically substituted alkynes, via a thiirenium ion, to give regioisomeric mixtures of (E)-b-chlorovinyl sulfenamides arising predominantly from anti-Markovnikov addition (eq 1).2,3
The sulfur-nitrogen bond of the alkyne adduct enhances this reagent's usefulness since the sulfenamide products are mild sulfur electrophiles, useful for the introduction of sulfur-substituted residues into organic molecules. The phthalimido group has been displaced with various nucleophiles such as carbanions,2-4,8,9 amines,2-4,10 thiols,11 and alcohols;12 the regio- and stereochemical integrity of the double bond is maintained during such displacements. This suggests that phthalimidosulfenyl chloride may be considered a synthetic equivalent of synthetically inaccessible sulfenyl chlorides such as t-butylsulfenyl chloride and N,N-bis(trimethylsilyl)aminosulfenyl chloride (eq 2).2-4
Reaction of the alkyne adducts with aluminum and boron hydride reagents such as Lithium Aluminum Hydride, Sodium Borohydride, or Lithium Triethylborohydride, however, leads to the formation of unexpected thiirane derivatives (eq 3).13 These can be desulfurized to give divinyl sulfides.
Phthalimidosulfenyl chloride can be added to alkenes to yield a-chloro thioethers5 which, after treatment with lithium aluminum hydride, produce episulfides (eq 4).6 Sodium borohydride is unsuccessful in transforming the alkene adduct to the episulfide. The alkene addition is stereospecifically trans and proceeds through a thiiranium ion intermediate, the opening of which is governed predominantly by steric factors and usually gives a predominance of the anti-Markovnikov addition product.14 As in the addition of phthalimidosulfenyl chloride to alkynes, the phthalimido group can also be displaced with nucleophiles.4
Good yields of b-keto thioadducts can be obtained from the reaction of phthalimidosulfenyl chloride with ketones at 0 °C using the required carbonyl compound as solvent (eq 5).5,7 b-Diketones and b-keto esters also react in this manner.7
In contrast, cyclohexanone does not react under the above conditions. The corresponding adduct can be formed by reaction of the trimethylsilyl enol ether with phthalimidosulfenyl chloride (eq 6).7
Helen M. Organ
Merck Research Laboratories, Rahway, NJ, USA