Generation of Ethyl Metathiophosphate by Thermal Fragmentation of O-Ethyl N-Substituted Phosphoramidothioates.

O-Ethyl N-1-adamantylphosphoramidothioate was synthesized and found to fragment on heating in inert solvents to form the pyrophosphate AdNHP(S)(OEt)OP(S)(OEt)OH. The proposed mechanism involves an elimination of the amine portion with release of ethyl metathiophosphate (EtOP(S)O), as was confirmed in previous work for the comparable structure with oxygen. This transient compound then phosphorylates the starting phosphoramidothioate. O-Ethyl N,N-diethylphosphoramidothioate was also synthesized, and while it gave a similar pyro compound on heating, the reaction mixture was more complex. Both phosphoramidothioates, however, served effectively as thiophosphorylating agents toward alcohols, a silanol, and the silanol groups on the surface of silica gel. Exploratory experiments showed that these phosphoramidothioates also could thiophosphorylate the OH group of a monoester of phosphoric acid, as well as that of phosphinic acids, forming anhydrides with the partial structure

Phospholes with Reduced Pyramidal Character from Steric Crowding. 2. Photoelectron Spectral Evidence for Some Electron Delocalization in 1-(2,4-Di-tert-butyl-6-methylphenyl)-3-methylphosphole.

Photoelectron spectroscopy has been explored as a tool to measure the flattening of the phosphorus pyramid in a phosphole as caused by a large, sterically demanding P-substituent. Earlier PE spectra had shown no difference in ionization energies (IE) for simple phospholes and their tetrahydro derivatives (both around 8.0-8.45 eV). Calculations of the Koopmans IE at the Hartree-Fock 6-31G level for 1-methylphospholane showed that, as is known for nitrogen, planarization at phosphorus markedly reduced the ionization energy value (8.74 to 6.29 eV). A reduction in IE also occurred on planarizing 1-methylphosphole, but to a lesser extent, being offset by increased electron delocalization (8.93 to 7.16 eV). This suggests that experimental comparison of IE for the unsaturated and saturated systems could be used to detect the presence of electron delocalization in the former. The IE experimentally determined for the crowded 1-(2,4-di-tert-butyl-6-methylphenyl)-3-methylphosphole was 7.9 eV, the lowest ever recorded for a phosphole. The corresponding phospholane had IE 7.55 eV. The difference in the values is attributed to electron delocalization in the phosphole. Calculations performed on the related model 1-(2-tert-butyl-4,6-dimethylphenyl)phosphole showed that the P-substituent adopted an angle of 55.7 degrees (DFT/6-31G level; 57.6 degrees at the HF/6-31 level) with respect to the C(2)-P-C(5) plane (for P-phenyl, 67.1 degrees and 68.3 degrees, respectively).

Phospholes with Reduced Pyramidal Character from Steric Crowding. 1. Synthesis and NMR Characterization of 1-(2,4-Di-tert-butyl-6-methylphenyl)-3-methylphosphole.

The sterically crowded 1-(2,4-di-tert-butyl-6-methylphenyl)-3-methylphosphole was synthesized by dehydrohalogenation of the corresponding 3,4-dibromophospholane, in order to probe the possibility that the steric congestion would cause some flattening of the phosphorus pyramid and an increase in electron delocalization. The phosphole was a recrystallizable solid with (31)P NMR delta 1.8. Semiempirical calculations indicated that the pyramidal shape was retained but was noticeably flatter than in 1-phenylphosphole. In the low energy conformation, the phosphole and phenyl ring planes are approximately orthogonal, with the 2-tert-butyl group in the less crowded position that is syn to the lone pair on phosphorus. The 6-methyl group is positioned under the phosphole ring. This conformational prediction was amply confirmed by several chemical shift and coupling effects in the (13)C NMR spectrum. The (1)H NMR spectrum displayed an unusually large four-bond coupling (6 Hz) of (31)P to the m-phenyl proton syn to the lone pair (and none to the anti-meta proton), consistent with the orthogonal conformation. The oxide of the phosphole showed more stability than that of less crowded phospholes and gave a (31)P NMR signal that was detectable over a several hour period at room temperature. The oxide proceeded to give the usual Diels-Alder dimer and also formed a cycloadduct with N-phenylmaleimide. The phosphoryl group of the latter was reduced with trichlorosilane to give the phosphine. This new 7-phosphanorbornene derivative gave the most downfield (31)P NMR shift (delta 153.3) of any member of this family, all of which are characterized by remarkable deshielding in the syn isomer.

Using medicinal chemistry to solve an old medical mystery.

The logic behind the traditional medicinal chemistry technique of designing a synthetic enzyme substrate to mimic a natural one is used to uncover the identity of the unknown cause of two legacy industrial diseases by comparing the reported symptoms to two side effects of a modern synthetic.

33S NMR spectra of sulfonium salts: calculated and experimental.

33S NMR chemical shifts were calculated by the scaled DFT and EMPI approaches for the fluoride, chloride and bromide of trimethylsulfonium ion (1) and S-methyltetrahydrothiophenium ion (2), in addition to the free cations. Experimental values were obtained for the iodides of 1 (delta +48, CS2 = 0 ppm) and 2 (delta +95), and were found to agree with the calculated values well within the standard deviation of 35 ppm (3.5% of the shielding range) established in earlier work for a great variety of sulfur compounds. An earlier literature value of delta +750 for the iodide of 2 is therefore to be replaced. Calculations provide a shift of delta +68 for S-methylthianium ion with equatorial methyl, indicating that the reported value of delta +670 for the iodide is also incorrect.

Bonding and 33S NMR chemical shielding in the thiophosphoryl group.

B3LYP and MP2 calculations at the 6-311 + G(nd,p) level (with n = 2 for second-row elements and n = 1 otherwise) were carried out using the atoms-in-molecules (AIM) approach to characterize the thiophosphoryl bond. A series of R(3)PS molecules were studied and compared with the corresponding R(3)PO systems. As with the phosphoryl bond, one cannot distinguish the thiophosphoryl bond from a standard P=S double bond by comparing bond distances. On the basis of the P=S bond in HP=S having a reference bond order of 2.0, the thiophosphoryl bond has a bond order of about 1.6. Examination of localized orbitals show that this bond is less polar than the corresponding PO bond. As with the phosphoryl bond, what sets the thiophosphoryl bond apart is the high degree of back-bonding that contributes to the delocalization index (and covalent bond order) and is the basis for its stronger than single bond character and short bond distance. (33)S NMR shielding calculations were also carried out and, in a few instances, compared directly with newly determined experimental shieldings.