Abstract: Bromination of (−)-4-hydroxy-N-methylmorphinan-6-one (3), prepared from natural morphine, with 1 mol of bromine in acetic acid, afforded the 1-bromo ketone 5. The structure of 5 was assigned by 13C-NMR.spectroscopy, and confirmed by X-ray diffraction analysis of its hydrobromide salt. It is suggested that monobromination of synthetic (±)-2,4-dihydroxy-N-formylmorphinan-6-one (7) takes in principle a similar course, although the 13C-NMR.spectrum of the primary reaction product 9 could not be measured because of insolubility in commonly used solvents. Monobromination of (−)-4-acetoxy-N-formylmorphinan-6-one (12) of the natural series, and of (±)-2,4-diacetoxy-N-formylmorphinan-6-one (8) of the synthetic series, followed by treatment of the monobrominated ketones with potassium carbonate in methanol resulted in closure of the O-bridge, and afforded after acid hydrolysis, the corresponding 4,5-epoxy-morphinan-6-ones (−)-16 and (±)-17 respectively. This variation of the ring closure reaction represents a novel and convenient method to convert 4-hydroxymorphinan-6-ones into their corresponding 4,5-epoxymorphinan-6-ones, without involving aromatic bromination and with only 1 mol of bromine.

Abstract: Das Phytoalexin Orchinol (3a) ist ausgehend von 2-(3,5-Dimethoxyphenyl)ethyliodid und 2,5-Dimethoxybenzoesaure im Gramm-Masstab zuganglich. Zentrale Schritte sind die Synthese des Gemische der Tetrahydrophenanthrenone 2a und 2b und deren direkte Dehydrierung zu 3a mit Pyridiniumhydrobromid-perbromid und nachfolgender Butyllithium-Behandlung. Polycyclic Compounds, XX1) A Simple Synthesis of Orchinol The phytoalexin orchinol (3a) is available in gram amounts starting from 2-(3,5-dimethoxyphenyl) ethyliodide and 2,5-dimethoxybenzoic acid. Key steps are the synthesis of a mixture of the tetrhydrophenanthrenones 2a/2b and their direct dehydrogenation with pyridinium hydrobromide perbromide followed by a subsequent treatment with n-butyllithium.

Abstract: The crystal structures of the title compound (1) and its hydrobromide (2) and methobromide (3) salts have been determined by X-ray crystallography in order to investigate the changes which take place in structure (1) on salt formation. Crystals of both (1) and (2) are monoclinic, with space group P21/c and Z= 4, and having unit cell dimensions respectively a= 12.021(1), b= 8.117(1), c= 13.562(2)A, β= 115.72(1)°, and a= 10.133(2), b= 16.965(4), c= 8.277(2)A, β= 102.55(2)°. Crystals of (3) are triclinic, space group P, and with Z= 2 in a unit cell of dimensions a= 7.929(2), b= 14.480(2), c= 6.549(1)A, α= 90.12(1), β= 98.56(2), γ= 95.37(2)°. Structure (1) was solved by direct methods, and (2) and (3) by the heavy-atom Patterson method; refinements were to R 0.041 for 2 165 independent refelctions in (1), to R 0.047 for 1 855 in (2), and to R 0.032 for 2 754 in (3). There is a systematic increase in CN bond length along the series; all such distances are longer, however, than normal values, as substantiated by vCN frequencies below 1 600 cm–1 in the i.r. spectra. Bond parameters for the pyran ring show an increase in pyrylium character on salt formation, the effect being largest in (3). Increased positive charge on the pyran rings in (2) and (3) is confirmed by shifts in their 1H and 13C n.m.r. signals relative to (1), though these reveal no obvious distinction between the two salts. There is a relatively short [2.34(4)A] linear N–H ⋯ Br hydrogen bond in the hydrobromide. Structural and spectroscopic data support an inversion mechanism for isomerisation about the CN bond in the imine (1), consistent with the observed low ΔG‡ value, while isomerisation in the two salts (with higher ΔG‡ values) is probably by a different mechanism.

Abstract: The syntheses of 9-oxobenzomorphans 10 and 12 are described. Both products exist in the cyclic forms 11 and 13 respectively. Hydrobromide and oxalate salts of the 9-oxobenzomorphan 1 when crystallized from methanol form stable methylhemiketals 4 and 5. Bromination of 5 yielded benzomorphan 8 which on treatment with sodium hydroxide produced, via 10, the cyclic hemiketal 11. Reaction of 8 with sodium hydrogen sulfide afforded, via 12, the cyclic hemithioketals 13.

Abstract: The invention relates to the new crystalline hydrochloride and the crystalline hydrobromide of 7s- [2- (2-amino-4-thiazolyl) -2-methoxy-iminoacetamido) -3-cephem-4-carboxylic acid pivaloyloxymethyl ester, process for their preparation, as well as pharmaceutical preparations containing these compounds.

Abstract: PURPOSE:A trihaloethane is heated in the presence of a diazabicycloalkene hydrohalide to produce the titled substance used as a monomer for high polymer synthesis or a synthetic intermediate in high selectivity CONSTITUTION:A trihaloethane such as 1,1,2-trichloroethane is heated at 230- 320 degC in the presence of a diazabicycloalkene hydrochloride or hydrobromide of the formula (n is 3-11, preferably 3,5, or 11) to produce a vinylidene halide such as vinylidene chloride The reaction may be conducted either in liquid or gas phase, however, when it is conducted in gas phase, the diazabicycloalkene hydrohalide is preferably supported on a carrier such as silica gel When it is conducted in liquid phase, a solvent may be used and a small amount of autioxidant may be added to the reaction system

Abstract: The 11α- and 11β-diethylaminoethyl ethers of 17α-ethynylestradol have been prepared from the intermediate alcohols (7a) and (7b) by direct alkylation with 2-N,N-diethylaminoethyl bromide hydrobromide followed by hydrogenolysis, deacetalization, and reaction with lithium acetylide. The two 11-diethylaminoethyl ethers of 17α-ethynylestradiol showed no significant estrogenic, anti-estrogenic, or post-coital activity.

Abstract: The synthesis, relative stereochemistry, and preliminary biological activity of ciramadol hydrochloride, a potent benzylamine analgesic, have been reported (Yardley et al., 1978). In view of the continued clinical interest in ciramadol (Staquet, 1980), an X-ray crystallographic study was performed both as a check on the relative configurations of the three adjacent chiral centers and to determine the absolute configuration. The actual determinations were made on a hydrobromide salt prepared specifically for this project. In addition, this compound offers the opportuni ty of observing the N§ . . Brhydrogen bond, which has been a subject of interest recently in these laboratories. It was also expected that the infrequently observed O-H 9 9 9 Brhydrogen bond would be present.

Abstract: Three electrophilic amide analogues of (S)-2,3-diaminopropionic acid (1, DAP) have been prepared as potential inhibitors of L-asparagine synthetase (ASase, from Novikoff hepatoma, EC 6.3.5.4). DAP was selectively blocked by the carbobenzoxy (Cbz) group to give 3-N-Cbz-DAP (2a). Esterification of 2a with isobutylene afforded tert-butyl 3-N-carbobenzoxy-(S)-2,3-diaminopropionate (3a), which was then blocked at the 2 position with the tert-butoxycarbonyl (Boc) group to give tert-butyl 2-[(S)-(tert-butoxycarbonyl)amino]-3-[(carbobenzoxy)amino]propionate (4). Selective cleavage of the Cbz group by H2/Pd gave the key intermediate tert-butyl 2-N-(tert-butoxycarbonyl)-(S)-2,3-diaminopropionate (5), which was acylated, via the N-hydroxysuccinimide esters, with bromoacetic acid, dichloroacetic acid, and fumaric acid monoethyl ester to give tert-butyl 2-[(S)-(tert-butoxycarbonyl)-amino]-3-(2-bromoacetamido)propionate (6a), tert-butyl 2-[(S)-(tert-butoxycarbonyl)amino]-3-(2,2-dichloroacetamido)propionate (6b), and tert-butyl 2-[(S)-(tert-butoxycarbonyl)amino]-3-(ethoxycarbonyl)acrylamido]-propionate (6c), respectively. Deblocking of 6a-c gave the corresponding amino acids (S)-2-amino-3-(2-bromoacetamido)propionic acid hydrobromide (7a), (S)-2-amino-3-(2,2-dichloroacetamido)propionic acid (7b), and ethyl N-[(S)-2-amino-2-carboxyethyl]fumarate (7c). By a slightly different procedure, 5 was converted in two steps to (S)-2-amino-3-acetamidopropionic acid hydrobromide (7d). The inhibition of ASase by 7a-c at 1 mM was 93, 19, and 37%, respectively, while 7d was without inhibition at 2 mM. Compounds 7a-c failed to increase the life span of mice infected with B16 melanoma.

Abstract: Semicarbazide hydrobromide which is isomorphous with SEM.HCl, was expected to belong to a new family of ferroelectrics. Dielectric, thermal and other studies on these crystals have yielded results which show many peculiarities but not confirmed ferroelectricity in the low temperature phase. As such a Laser Raman spectrosocopic study of oriented singe crystals of SEM.HBr was made at 298°K and at 253°K. The results have been correlated with structural features and compared with SEM.HCl.