Sir:We wish to report the first determination of the molecular parameters of a phosphole. The synthesis of 1 -benzylphosphole (11) resembled that already employed for l-methylphosphole,2 and made use of l-benzyl-3,4-dibromophospholane oxide (I, mp 159-160', analyzing correctly) as the key intermediate. As before, some of the corresponding 3-phospholene was formed but was removed on extraction with 2 N hydrochloric I1 acid. that which proved most successful is shown below.Several methods of obtaining I were devised; Br Iv C,H,CH,MgCIThe reduction of the butadiene-phosphorus tribromide cycloadduct (111) to form 1-bromo-3-phospholene [IV, 34%, bp 64-67' (27 mm), 31P nmr signal -11 1.4 ppm relative to 85 % phosphoric acid] is a new reaction of considerable synthetic value in phospholene chemistry; details on the procedure will be published elsewhere. Compound V was identified by quaternization with methyl bromide to form the same salt obtained from 1 -methyl-3-phospholene with benzyl bromide.5 I-Benzylphosphole was considerably more stable than I-methylphosphole and distilled without decomposition at 71-72' (0.2 mm); it had mp 34-34.5' and gave the correct analysis. It resembled 1 -methylphosphole in having low basicity, a uv maximum in 95 % ethanol at 286 mp (log t 3.65), and a 31P nmr signal (-7.9 ppm) Figure 1. Molecular structure of 1-benzylphosphole. Molecular dimensions are P-Cs = 1.786, P-C5 = 1.780, P-CB = 1.858, CZ-C3 = 1.343, C3-C4 =-1.438, C4-C5 = 1.343, c & 7 = 1.506, mean phenylC-C = 1.382A; CzPC5 = 90.7", CzPC6 = 106.1", C j P G = C3C4Cs = 114.1", PS6C7 = 116.4". Standard deviations of distances are &0.005 A for P-C bonds and =t0.006 A for C-C bonds, while those for angles are +0.2" for CPC angles and jz0.4" for CCC angles. 105.9", PC2C3 109.9", PCjCa = 110.1", CzC3Ca = 114.1",showing considerable deshielding relative to the corresponding 3-phospholene (V, +23.5 pprn). Its ring protons were similarly strongly deshielded (multiplet, 6 6.3-7.3 ppm, partly merged with phenyl protons), and the benzylic CH2 group (6 3.01 pprn) was not detectably coupled with phosphorus. Its mass spectrum confirmed its monomeric character (M+ at mje 174, 38.8 % of C7H7+ base peak). It is sensitive to oxygen and can be quaternized with alkyl halides. Crystals of I1 obtained from a melt pave cell dimensions a = 17.62, b = 14.60, c = 7.67 A , and belong to the orthorhombic system with eight units of CllHllP occupying general positions of space group Pbca. A total of 135 1 independent structure amplitudes were derived from visually estimated intensities recorded by equiinclination Weissenberg photography of the hk0-7 layers. The structure was solved by the heavy-atom method and refined by full-matrix least-squares calcu-lations6 to the present conventional R of 0.073. The molecular dimensions are given in the legend of Figure 1.Comparison of the phosphole dimensions with those of the heteroaromatics furan, pyrrole, and thiophene is of particuJar interest. The average P-C,,, bond length 1.783 A is significantly less7 than the su...

A series of novel tetrahydropyridinecarboxamide TRPV1 antagonists were prepared and evaluated in an effort to optimize properties of previously described lead compounds from piperazinecarboxamide series. The compounds were evaluated for their ability to block capsaicin and acid-induced calcium influx in CHO cells expressing human TRPV1. The most potent of these TRPV1 antagonists were further characterized in pharmacokinetic, efficacy, and body temperature studies. On the basis of its pharmacokinetic, in vivo efficacy, safety, and toxicological properties, compound 37 was selected for further evaluation in human clinical trials.

loss of intensity was observed during the experiment as judged by regular monitoring of three reference reflections so that a single scale factor could be used. No corrections for absorption were deemed necessary.Crystal Data for o-Bromobenzoate 6.-CijHaiBrO, had formula weight 547.4, orthorhombic, a = 11.25 (2), b = 26.63 (4), c = 8.96 (2) A, U = 2685 Á8, Dm = 1.34 (by pycnometry with an aqueous Znl solution), Z = 4, £)" = 1.35, F (000) = 1136. Space group P2i2i2i. Precession photography, Mo Ka radiation, X 0.7107 Á, µ 17 cm-1.Structure Determination and Refinement.-The structure was solved by the heavy-atom method in the usual way, and five cycles of Fourier refinement with a single, overall, isotropic thermal parameter, B = 4.0 A2, gave B = 0.22.Further refinement of the structural parameters was by blockdiagonal least-squares methods. With anisotropic thermal parameters assumed only for the bromine atom, B was 0.118 at convergence. Inclusion of the anomalous dispersion terms16 for bromine in the structure factor calculations gave B = 0.123 and 0.116 for the two possible enantiomeric structures. By Hamilton's ñ-factor ratio test17 a significant distinction is implied between the two absolute configurations at the 99.5% confidence (16) D.

Zur Synthese des substitutierten Triaminopyridins (VII) wird das leicht zugängliche Dichlornitropyridin (I) durch stufenweise Substitution der Chloratome durch NH3 (II) bzw. p‐Fluorbenzylamin (IV) in (V) übergeführt.

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