Hydrobromide Salt Research Articles

Intraventricular 6-hydroxydopamine increases thyrotropin-releasing hormone (TRH) content in regions of rat brain

Rats were given intraventricular (ivt) injections of various doses (50–400 μg, hydrobromide salt) of 6-hydroxydopamine (6-OHDA) and killed 1, 3 or 6 days later. Brains were removed, dissected into 11 regions, and the thyrotropin-releasing hormone (TRH) content of each region was measured by radioimmunoassay. 6-OHDA (400 μg) caused significant elevations in the TRH content of 6 regions: olfactory bulb, anterior cortex, brainstem, posterior cortex, hippocampus, and amygdala-piriform cortex. The magnitude of these increases ranged from 59% in olfactory bulb to 497% in hippocampus and was, in all cases, greatest at 3 days. These results suggest that the TRH content of certain brain regions may be regulated by catecholamine neurotransmitters.

Evaluation of infrared spectroscopic techniques for analysing chitosan

AbstractThe use of the 3450 cm−1 absorption band as an internal standard in the determination of the extent of N‐acetylation of chitosan from the absorbance of the amide I band at 1655 cm−1 was studied. The results show that the technique gives consistent results that are relatively unaffected by whether the sample is air‐dried or oven‐dried. A number of chitosan samples, covering the range of N‐acetyl values from 14% to 72% were analysed by three techniques: infrared spectroscopy using the ratio A1655/A3450, hydrobromide salt titration and residual salicylaldehyde determination. There is a very good correlation between the results from infrared spectroscopy and those from the other two analytical techniques, confirming the validity of the former technique.

Allopurinol prodrugs. III. Water-soluble N-acyloxymethyl allopurinol derivatives for rectal or parenteral use

Nine amino acid esters of 1-(hydroxymethyl)allopurinol were synthesized and evaluated as potential water-soluble prodrugs of allopurinol with the aim of developing preparations suitable for parenteral and/or rectal administration. Hydrochloride or hydrobromide salts of all the 1-acyloxymethyl derivatives exhibited a water-solubility greater than 20%. The kinetics of hydrolysis of the compounds was studied in aqueous solution and in human plasma solutions at 37°C. Complete reversion to allopurinol was observed in all cases, the maximum stability of the derivatives occurring at pH < 4. The susceptibility of the derivatives to undergo enzymatic hydrolysis varied widely, the observed half-lives in 80% human plasma ranging from 3 to 140 min. It was concluded that N 1-acyloxymethyl derivatives of allopurinol containing an amino group in the acyl moiety are potentially useful as parenteral delivery forms of the parent drug. Furthermore, compounds containing a weakly basic amino group (pK a 6–7.5) may be useful as prodrugs to enhance the rectal absorption of allopurinol as assessed on the basis of the water-solubility and lipophilicity of the derivatives.

Polymer‐supported bases, 2. Polystyrene‐supported 1,8‐diazabicyclo[5.4.0]undec‐7‐ene as reagent in organic syntheses

AbstractPolystyrene‐supported 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (PDBU) was prepared by the reaction of lithiated 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) with chloromethylated or ω‐bromoalkylated polystyrene resins. PDBU is effective as reagent for dehydrobromination and esterification. The reactivity of PDBU in dehydrobromination is lower than that of DBU. In the case of esterification, PDBU with 19% ring substitution exhibits almost the same reactivity as DBU. PDBU, regenerated from the hydrobromide salt, can be re‐used without decrease in reactivity.

Evaluation of High-Performance Liquid Chromatography and Gas Chromatography for Quantitation of Dextromethorphan Hydrobromide in Cough-Cold Syrup Preparations

A rapid and sensitive high-performance liquid chromatographic (HPLC) procedure is described for the analysis of the antitussive dextro-methorphan hydrobromide in several cough-cold syrup preparations and compared with a gas chromatographic (GC) procedure. In the HPLC procedure, the active ingredient is analyzed as the hydrobromide salt by dilution in the mobile phase and separation on a reverse-phase cyano column. In the GC method, the active ingredient is analyzed as the free base, in which an aqueous solution of the antitussive is made alkaline and extracted with dichloromethane before injection onto the GC column. Excellent resolution of the antitussive agent was obtained by both systems; however, the HPLC assay is preferred for routine analysis (RSD 1%), as compared with the GC assay (RSD 4%).

N2′‐acetyl‐6‐diacetoxymethylpterin

AbstractTreatment of folic acid with bromine in 48% hydrobromic acid gives the hydrobromide salt of 6‐formylpterin (1), and acetylation of 1 with recovered acetic anhydride leads to N2′‐acetyl‐6‐diacetoxymethylpterin (3).

Apomorphinans from Isoquinolines: Grewe cyclization of 1‐(2‐hydroxybenzyl)‐N‐methyloctahydroisoquinoline and its O‐methyl ether

AbstractWolff‐Kishner reduction of the optically active ketomorphinan 5 afforded the optically active morphinan 6 differing chromatographically and spectroscopically from the material obtained in a Grewe‐cyclization of the isoquinoline 1. A single crystal X‐ray analysis of a hydrobromide salt of a phenolic amine obtained from 1 and 2 with refluxing hydrobromic acid showed this compound to be the N‐methylapomorphinan 4.

Reactions with α-substituted cinnamonitriles: A novel synthesis of arylpyrimidines

α-Benzoyl- and α-ethoxycarbonylcinnamonitrile derivatives 1a-c and ld-f reacted with benzamidine hydrochloride ( 2) in boiling pyridine to give the fully aromatized aryl-pyrimidine derivatives 3a-c and 6a-c respectively. In contrast the a-cyanocinnamonitrile derivatives 1g-j reacted with 2 under the same conditions to form the dihydropyrimidine derivatives 7a-d. Compounds 7a,b could be dehydrogenated to the fully aromatized analogues 8a,b as hydrobromide salts by treatment with bromine in acetic acid. The free basic compound 8a was isolated from 8a.HBr by neutralisation. A scheme for the reaction steps of 1 and 2 is proposed and the structures of the synthesised compounds were proved by chemical methods and spectral studies.

Crystal and molecular structure of analgesics, I. Ciramadol hydrobromide, C15H23O2N � HBr

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.

Structure Determination of Brominated Morphinan‐6‐ones by 13C‐NMR. Spectroscopy: A novel closure of the oxygen bridge using 4‐acetoxymorphinan‐6‐ones

AbstractBromination 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.

ChemInform Abstract: BIVALENT METAL COMPLEXES OF 1,11‐DIAMINO‐3,6,9‐TRITHIAUNDECANE AND THE CRYSTAL STRUCTURES OF ADDUCTS WITH NICKEL(II) AND COPPER(II) BROMIDES

AbstractDie äquimolare Umsetzung von Cu(II)‐ oder Ni(II)‐acetat mit dem aus S(CH2 ‐CH2 ‐SNa)2 und Br‐CH,‐CH,‐NH2°C HBr dargestellten Dihydrobromid des fünfzähnigen Titelliganden (Ausb. 83%) führt zu den oktaedrischen Bromo‐bromid‐Komplexen (Ia) (keine Ausb.‐Angabe).

9-Oxobenzomorphans. IV. 9-Oxo-5-[3″-(1″-hydroxypropyl)]- and 9-oxo-5-[3″-(1″-sulfidrylpropyl)]-6,7-benzomorphans as cyclic hemiketals and hemithioketals

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.

The effect of salt formation on the molecular structure and charge distribution in imines: the crystal and molecular structures and the ultraviolet, infrared, and the 1H and 13C nuclear magnetic resonance spectra of 2,6-dimethyl-4-(p-nitrophenylimino)pyran and its hydrobromide and methobromide salts

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.

Bivalent metal complexes of 1,11-diamino-3,6,9-trithiaundecane and the crystal structures of adducts with nickel(II) and copper(II) bromides

The hydrobromide salt of the quinquedentate ligand 1,11-diamino-3,6,9-trithiaundecane (L1) reacts with copper(II) and nickel(II) acetates to form [MBrL1] Br (M = Cu or Ni). By anion-exchange reactions a whole series of compounds of general formula [MXL1]X′, X = CI, Br, I, or NCS, X′= Cl, Br, I, NCS, PF6, or ClO4, were prepared. Results of conductivity and spectroscopic measurements indicate that these species all contain six-co-ordinate metal ions. For two compounds the geometry was confirmed by X-ray crystallography. Crystals of [CuBrL1] Br· H2O are monoclinic, space group P21/m, Z= 2, a= 5.559(7), b= 10.009(11), c= 14.720(13)Å, and β= 90.0(1)°. Crystals of [NiBrL1] Br are orthorhombic, space group Pmnb, Z= 4, a= 10.185(12), b= 16.963(12), and c= 9.028(7)Å. 843 and 968 Independent reflections above background have been collected on a diffractometer and refined to R 0.102, 0.067 respectively for M = Cu, Ni. Both structures contain discrete cations of formula [MBrL1]+ which have crystallographically imposed Cs symmetry. The metal atoms are in distorted octahedral environments with bond lengths [M = Cu: M–N 2.03(2), M–S 2.340(6), 2.576(9), M–Br 3.310(5)] and [M = Ni : M–N 2.074(17), M–S 2.393(6), 2.437(8), M–Br 2.578(5)]. The Cu–Br and the longer of the Cu–S bonds are mutually trans and are particularly long due to the Jahn–Teller effect.

Investigation and Identification of the Bromination Products of Dimethoxyamphetamines

The qualitative analysis of the aromatic bromination products of the 6 isomeric dimethoxyamphetamines and their hydrochloride or hydrobromide salts is described. Their ultraviolet, mass, and proton magnetic resonance spectra are not sufficiently different for distinction but infrared spectra allow a positive identification to be made and reference spectra are provided for the bromination products of 2,4-, 2,5-, 2,6-, 4,5-, and 3,5-dimethoxyamphetamines. The application of gas-liquid and thin layer chromatography for the analysis of these products is discussed. The bromination of 2,3-dimethoxyamphetamine consistently gave mixtures which could not be separated satisfactorily; spectra are included for completeness of the comparison of products.

Synthesis and antiviral and antimicrobial activity of certain 1-.beta.-D-ribofuranosyl-4,5-disubstituted imidazoles

Starting with AICA ribonucleoside the following nucleosides were prepared. Methyl 5-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carboxylate (5) was converted into methyl 5-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carboxylate (6) via diazotization in the presence of cuprous chloride. Similarly, 5-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuanosyl)imidazole-4-carbonitrile (9) was converted into 5-chloro-, 5-bromo-, and 5-iodo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carbonitrile derivatives. These 5-halogenated imidazole nucleosides were treated with several nucleophiles such as ammonia, hydroxylamine, and hydrogen sulfide to provide, respectively, 5-haloimidazole-4-carboxamide, 5-haloimidazole-4-carboxamidoxime, and 5-haloimidazole-4-thiocarboxamide ribonucleosides. 5-Chloro- or 5-bromo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carbonitrile was treated with potassium hydrosulfide to yield 5-mercapto-1-beta-D-ribofuranosylimidazole-4-thiocarboxamide (16). The catalytic reduction of 5-chloro- or 5-bromo-1-beta-D-ribofuranosylimidazole-4-carboxamidoxime provided 1-beta-D-ribofuranosylimidazole-4-carboxamidines as their hydrochloride and hydrobromide salts, respectively. These nucleosides were tested for in vitro antiviral, antifungal, and antibacterial activity. The 5-halo analogues of 1-beta-D-ribofuranosylimidazole-4-carboxamide showed significant antiviral activity whereas compound 16 was found inhibitory to fungi.

Sorption of water vapour by poly-L-glutamic acid, poly-L-lysine and their salts and some chemically modified derivatives

Isotherms for the sorption of water by poly-L-lysine and poly-L-glutamic acid, their hydrobromide and sodium salts respectively, and six chemically modified derivatives of the polypeptides have been measured gravimetrically.

5-Allyl-9-oxobenzomorphans. Part 2. The Crystal and Molecular Structure of an Unusual Product of Dequaternization of 5-Allyl-9-oxobenzomorphan Methobromide

The synthesis of 5-allyl-2'-methoxy-9-oxo-6,7-benzomorphan (5b) is described. The 10-hydroxy-2-methyl-1,11-propano-9H-indeno-1,2,10,11-tetrahydro[2,1-c]pyridine (7a) and the corresponding 6-methoxy derivative (7b) are unexpected products of pyrolysis of 5-allyl-2-methyl-9-oxobenzomorphan methobromide (4a) and 5-allyl-2′-methoxy-2-methyl-9-oxobenzomorphan methobromide (4b) respectively. The molecular structure of 7a (C16H19NO) has been determined from spectral and microanalytical data, and confirmed by X-ray single crystal analysis on its hydrobromide salt using the heavy atom technique. The crystals of [C16H20NO]+Br− are monoclinic, P21/a, with a = 13.724(2), b = 14.022(3), c = 7.495(2) Å, β = 97.33(5)°, and Z = 4. The crystal structure has been refined by block-diagonal least-squares calculations to R and Rw = 0.036 for the 2197 observed reflections. The N atom has planar trigonal coordination, and forms one double and two single C—N bonds of lengths 1.273(4), 1.465(4), and 1.474(4) Å, respectively. The Br is hydrogen-bonded to O. The N and O atoms are trans.

Infrared Identification Test for Scopolamine as the Hydrobromide

The method of preparation of scopolamine hydrobromide affects the infrared (IR) spectrum of the product. A column chromatographic procedure is used to both isolate the drug from tablets and injections and form the hydrobromide salt. This yields reproducible IR spectra and thus constitutes an identity test for scopolamine hydrobromide.

Reaction of ligating dinitrogen and tetrahydrofuran to form tetrahydropyridazido-complexes

In the presence of methyl bromide visible irradiation causes the reaction of tetrahydrofuran with the complexes [M(N2)2(dpe)2](M = W or Mo; dpe = Ph2PCH2CH2PPh2) to form tetrahydropyridazido-complexes [MBr(N2C4H7)(dpe)2] and their hydrobromide salts [MBr(N2C4H8)(dpe)2]Br; in this reaction the ligating dinitrogen appears to have replaced oxygen directly in the tetrahydrofuran ring.