Reactions of 3-isopropenyltropolones with bromine and N-bromosuccinimide: Formation of 8H-cyclohepta[b]furan-8-one derivatives

3-Isopropenyltropolones 1a-c were treated with bromine in carbon tetrachloride to give 3-methyl-8H-cyclohepta[b]furan-8-ones 2a-c and their corresponding 7-bromo-substituted compounds 3a-c , while reactions in acetic acid gave the bromo-substituted compounds 3a-c . On the other hand, bromination of 1a-c with N-bromosuccinimide afforded 7-bromo-3-(2-bromo-1-methylethenyl)tropolones 5a-c . The compound 2a was treated with bromine to give 2-bromo-3-methyl-8H-cyclohepta[b]furan-8-one ( 4 ). The tropolones 5a-c were heated in the presence of potassium carbonate to give the cyclized compounds 3a-c .     

Thietanyl protection in the synthesis of 1-alkyl-8-bromo-3-methyl-3,7-dihydro-1<Emphasis Type="Italic">H</Emphasis>-purine-2,6-diones

The protection of the 7-NH group in 8-bromo-3-methyl-3,7-dihydro-1H-pyrine-2,6-dione during the synthesis of 7-ubsubstituted 1-alkyl-8-bromo-3-methyl-3,7-dihydro-1H-pyrine-2,6-diones with a thienyl group was applied that was introduced by the reaction with 2-chloromethylthiirane. The thietanyl protection was removed by treating with sodium alcoholate after the oxidation with hydrogen peroxide to thietane 1,1-dioxide group.     

Synthesis and structure of 3-arylidene and 3-hetarylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones and their affinity toward CNS benzodiazepine receptors

The condensation of 5-aryl-7-bromo-1,2-dihydro-3H-1,4-benzodiazepin-2-ones with aromatic aldehydes gives 5-aryl-3-arylidene-and 5-aryl-7-bromo-3-hetarylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones. X-ray diffraction structural analysis yielded the molecular and crystal structures of 7-bromo-3-(4′-methoxybenzylidene)-5-phenyl-1,2-dihydro-3H-1,4-diazepin-2-one and showed that this compound has cis configuration. Radioligand analysis was used to study the affinity of these products toward central nervous system and peripheral benzodiazepine receptors. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1213–1225, August, 2007.     

Bromination of 5,7,4′-Trimethoxyflavanone

Three new 8-bromoflavonoids, 3,3,8-tribromo-5,7,4′-trimethoxyflavanone ( 5 ), 3,8-dibromo-5,7,4′-trimethoxyflavanone ( 7 ) and 3,8-dibromo-5,7,4′-trimethoxyflavone ( 6 ); and two known 8-bromoflavones, 8-bromo-5,7,4-trimethoxyflavone ( 8 ) and 8-bromo-5-hydroxy-7,4′-dimethoxyflavone ( 9 ), have been isolated on bromination of 5,7,4′-trimethoxyflavanone ( 4 ).     

Synthesis and Antibacterial Activity of Caffeine Derivatives Containing Amino-Acid Fragments

Chemistry of Natural Compounds - Cross-coupling of 8-bromocaffeine, 8-bromo-1-butyltheobromine, or 8-bromo-7-butyltheophylline with α-, β-, or ω-amino-acid methyl or t-butyl ester...     

Pyrimidine derivatives. VI. Synthesis of mono-, di-, tri-, and tetrabromo-substituted pyrimidine derivatives

The following bromo-2,4(1H,3H)-pyrimidinediones possessing a bromo substituent at the 5-position and side chains at the 1- and 6-positions were prepared. The three types of mono-bromo derivatives are: 1-(bromoalkyl)-3,6-dimethyl- 3a-d , 5-bromo-3,6-dimethyl-1-(hydroxyalkyl)- 4a-d , and 1-(acetoxyalkyl)-5-bromo-3,6-dimethyl-2,4(1H,3H)-pyrimidinediones 11a-d . The three types of dibromo derivatives are: 5-bromo-1-(bromoalkyl)-3,6-dimethyl- Sa-d , 1-(acetoxyalkyl)-5-bromo-6-bromomethyl- 8a, 8c , and 8d , and 5-bromo-6-bromomethyl 1-(hydroxyalkyl)-2,4(1H,3H)-pyrimidinediones 9a, 9c , and 9d . Likewise one group of tribromo and one group of tetrabromo derivatives are: 5-bromo-1-(bromoalkyl)-6-bromomethyl -7a-d and 5-bromo-1-(bromoalkyl)-6-dibromomethyl-2,4(1H,3H)-pyrimidinediones 6a-d .     

Total synthesis of (±)-fangchinoline

(±)-Fangchinoline was synthesized by condensation of (±)-1-(3-bromo-4-methoxy-benzyl)-2-methyl-6-methoxy-7-hydroxy-8-bromo-1,2,3,4-tetrahydroisoquinoline ( 2 ) and (±)-1-(4-hydroxy-benzyl)-2-methyl-6-methoxy-7-hydroxy-1,2,3,4-tetrahydroisoquinoline ( 3 ) in the presence of copper, pyridine and potassium carbonate.     

The influence of a t-Butyl group on the conformational equilibrium and the Hydrogen Bromide catalyzed isomerization of 2-Bromocyclohexanones

The trans and cis diastereoisomers of 2-bromo-6-t-butylcyclohexanone (7 and 8) and of 2-bromo-3-t-butylcyclohexanone (10 and 9) have been prepared and subjected to hydrogen bromide catalyzed isomerization. Whereas bromoketones 7 and 8 underwent only epimerization, isomers 9 and 10 were completely converted into an equilibrium mixture of cis- and trans-2-bromo-5-t-butylcyclohexanone (12 and 13). The spectral parameters (IR, UV, NMR), as well as the equilibrium distribution of the couple 7-8, were consistent with chair conformations for compounds 7, 8 and 9, but indicated for isomer 10 a flexible form in which both the bromine-t-butyl steric interaction and the electrostatic repulsion between Br and CO group are relieved.     

Simple preparation of 7-alkylamino-2-methylquinoline-5,8-diones: regiochemistry in nucleophilic substitution reactions of the 6- or 7-bromo-2-methylquinoline-5,8-dione with amines

7-Alkylamino-2-methylquinoline-5,8-diones (7) were prepared from 6-bromo-2-methylquinoline-5,8-dione (2) not from 7-bromo-2-methylquinoline-5,8-dione (1). The chemistry of the transformation of 6-bromo-2-methylquinoline-5,8-dione (2) and various alkylamines, such as piperidine, 2-methylaziridine, benzylamine, n-butylamine, cyclohexylamine, t-butylamine, and ammonia, to 7-alkylamino compounds 7 as well as the transformation of 7-bromo compound 1 and the alkylamines to 6-alkylamino-2-methylquinoline-5,8-diones 11 was studied. The efficient and simple synthetic routes of the key intermediates, 6- and 7-bromo-2-methylquinoline-5,8-diones (2 and 1), from 5,8-dihydroxy-2-methylquinoline (15) and 5,7-dibromo-8-hydroxy-2-methylquinoline (9), respectively, were developed. We also proposed the mechanism for the unusual regioselectivity on the nucleophilic amination of 6- and 7-bromo-2-methylquinoline-5,8-diones (2 and 1).     

Brominated hydroxyquinoline as a photolabile protecting group with sensitivity to multiphoton excitation

The synthesis and photochemistry of a new photolabile protecting group for carboxylic acids based on 8-bromo-7-hydroxyquinoline (BHQ) is described. BHQ possesses a greater single photon quantum efficiency than 4,5-dimethoxy-4-nitrobenzyl ester (DMNB) and 6-bromo-7-hydroxycoumarin-4-ylmethyl (Bhc), and it has sufficient sensitivity to multiphoton-induced photolysis for use in vivo. Its increased solubility and low fluorescence make it quite useful as a caging group for biological messengers. [structure: see text]     

Formation of novel polycyclic cage compounds through ‘uncaging’ of readily accessible higher cage compounds

The synthesis of the novel cage compounds 7-halomethyl-8-(carbomethoxy)tetracyclo[4.2.1.1^4,7.0^2,5]deca-3-(11)-ene-10-ones, methyl-4-methylene-6-oxopentacyclo[5.4.0.0.^2,5.0^3,10.0^7,9]undecane-9-carboxylate, 3-chloromethyl-4-(carbomethoxy)tetracyclo[4.2.1.1.^3,8.0^2,5]deca-7(11)ene-10-one, 2-bromo-5-methyl-8-methylene-6-oxotricyclo[5.3.0.0^3,9]decane-4-carboxylic acid and 2-bromo-5-methyl-8-methylene-6-oxotricyclo[5.3.0.0^3,9]decane-4-methyl carboxylate, achieved through base catalyzed rearrangement, is described.     

Quinazolines. 3*. synthesis of 6-bromo-8-chloro-sulfonylquinazoline-2,4(1h,3h)-dione and its interaction with nucleophilic reagents

6-Bromo-8-chlorosulfonylquinazoline-2,4(1H,3H)-dione was obtained from 6-bromoquinazoline-2,4(1H,3H)-dione and chlorosulfonic acid in place of the expected 6-bromo-7-chlorosulfonyl-quinazoline-2,4(1H,3H)-dione. Interaction of the product with water, alcohols, ammonia, aliphatic and heterocyclic amines gave 6-bromo-8X-quinazoline-2,4(1H,3H)-diones (X = SO₂OH, SO₂OAlk, SO₂NR¹R²), and, by reduction with SnCl₂·2H₂O in hydrochloric acid, 6-bromo-8-mercaptoquinazoline-2,4-dione was obtained.     

Reaction of 5-nitrospiro[benzimidazole-2,1′-cyclohexane] 1,3-dioxide with electrophilic reagents: Bromine and nitric acid

Reactions of 5-nitrospiro[benzimidazole-2,1′-cyclohexane] 1,3-dioxide with bromine and nitric acid lead to the electrophilic substitution of the hydrogen atom in the meta-position with respect to the nitro group. At thebromination the primarily formed 4-bromo-6-nitrospiro[benzimidazole-2,1′-cyclohexane] 1,3-dioxide when kept in the solution loses an oxygen atom forming 4-bromo-6-nitrospiro[benzimidazole-2,1′-cyclohexane] 1-oxide and an isomerization product, 8-bromo-6-nitrospiro[3H-[2,1,4]benzoxadiazine-3,1′-cyclohexane] 4-oxide. The latter exposed to light turns into 4-bromo-6-nitrospiro[benzimidazole-2,1′-cyclohexane] 1,3-dioxide. The reaction of the initial 1,3-dioxide with nitric acid afforded 4,6-dinitrospiro[benzimidazole-2,1′-cyclohexan]-7-ol 1-oxide whose heating in o-dichlorobenzene resulted in 3,5-dinitro-1,8-diazatricyclo[7.5.0.0^2,7] tetradeca-2(7),3,5,8-tetraen-6-ol.     

Synthesis of the reported structure of crassiflorone, a naturally occurring quinone isolated from the African ebony Diospyros crassiflora, and regioisomeric pentacyclic furocoumarin naphthoquinones

A synthesis of the structure reported for the natural product crassiflorone, a furocoumarin naphthoquinone, is described. The key steps are a Diels-Alder reaction to form 2-bromo-8-hydroxy-6-methylnaphthoquinone, followed by O-protection and copper(II) mediated coupling to 4-hydroxy-5-methylcoumarin to establish the pentacyclic framework whose structure was unambiguously confirmed by X-ray crystallography. Since the spectroscopic data of the synthetic material did not match those reported for the natural product, three further regioisomeric furocoumarin naphthoquinones were prepared by copper(II) mediated coupling of 4-hydroxy-5- or 8-methyl coumarins with 5-benzyloxy-2-bromo-7-methyl- or 8-benzyloxy-2-bromo-6-methyl-1,4-naphthoquinone. Again the spectroscopic data did not match those of the natural material and therefore the true structure of crassiflorone remains unknown.     

Synthesis and crystal structures of 7,8-bromo (dibromo)-3-tert-butylpyrazolo[5,1-c][1,2,4]triazines

Structural Chemistry - Single crystal structures in a series of 7-bromo-, 8-bromo-, and 7,8-dibromo-3-tert-butylpyrazolo[5,1-c][1,2,4]triazin-4(1H)-ones have been investigated by X-ray diffraction....     

Synthesis of a new class of bisheterocycles via the Heck reaction of eudesmane type methylene lactones with 8-bromoxanthines

The eudesmane-type methylene lactones (isoalantolactone, alantolactone, 4,15-epoxyisoalantolactone, 2′,2′-dichloro-4H-spiro[cyclopropane-1′,4-eudesma-11(13)-en-8β,12-olide], and alantolactone) react with 8-bromoxanthines (8-bromocaffeine, 8-bromotheobromine, 8-bromo-3-butyltheobromine, 8-bromotheophylline, 8-bromo-9-butyltheophylline) under Heck reaction conditions to produce the target (E)-13-(2,6-dioxo-2,3-dihydro-1H-purin-8-yl)eudesma-4(15),11(13)-dien-8β,12-olides and the subsequent endocyclic isomers - 11-(2,6-dioxo-2,3-dihydro-1H-purin-8-yl)-13-normethyleudecma-4(15)-7(11)-dien-8α,12-olides. It was revealed that the yield and product ratio depends on the reaction conditions and the structure of methylene lactone. The effectiveness of Pd(OAc)₂–caffeine catalytic system has been demonstrated in this reaction. The electric eel acetylcholinesterase inhibitory activity of the eudecmanolide-xanthine hybrids was evaluated. Among the new type bisheterocycles compound 27 with butyl and 2-oxodecahydronaphtho[2,3-b]furan-3(2H)-ylidene)methyl substituents at C-7 and C-8 of the xanthine core showed moderate activity with IC₅₀ value of 40 μM.     

液质联用同时测定大鼠尿液中6种苯二氮卓类药物

建立高效液相色谱串联质谱法同时测定大鼠尿液中的6种苯二氮卓类药物(BZDs).以乙酸乙酯为萃取溶剂,经液-液萃取前处理后检测.以地西泮为内标,流动相为甲醇-0.01％甲酸+5 mmol/L甲酸铵,梯度洗脱,柱温为40℃;流速为0.3 mL/min;进样量为2 μL,质谱采用电喷雾离子源正离子模式(ESI+).8-溴-1...     

Thermische Lactonisierung von Estern γ-Brom-α, β-ungesättigter Carbonsäuren zu Δα-Butenoliden. Direkte γ-Bromierung von α, β-ungesättigten Säuren

By heating with iron powder at 120–150° some γ-bromo-α, β-unsaturated carboxylic methyl esters, and, less smothly, the corresponding acids, were lactonized to Δ^7alpha;-butenolides with elimination of methyl bromide. The following conversions have thus been made: methyl γ-bromocrotonate ( 1c ) and the corresponding acid ( 1d ) to Δ^α-butenolide ( 8a ), methyl γ-bromotiglate ( 3c ) and the corresponding acid ( 3d ) to α-methyl-Δ^α-butenolide ( 8b ), a mixture of methyl trans- and cis-γ-bromosenecioate ( 7c and 7e ) and a mixture of the corresponding acids ( 7d and 7f ) to β-methyl-Δ^α-butenolide ( 8c ). The procedure did not work with methyl trans-γ-bromo-Δ^α-pentenoate ( 5c ) nor with its acid ( 5d ). Most of the γ-bromo-α, β-unsaturated carboxylic esters ( 1c, 7c, 7e and 5c ) are available by direct N-bromosuccinimide bromination of the α, β-unsaturated esters 1a, 7a and 5a ; methyl γ-bromotiglate ( 3c ) is obtained from both methyl tiglate ( 3a ) and methyl angelate ( 4a ), but has to be separated from a structural isomer. The γ-bromo-α, β-unsaturated esters are shown by NMR. to have the indicated configurations which are independent of the configuration of the α, β-unsaturated esters used; the bromination always leads to the more stable configuration, usually the one with the bromine-carrying carbon anti to the carboxylic ester group; an exception is methyl γ-bromo-senecioate, for which the two isomers (cis, 7e , and trans, 7d ) have about the same stability. The N-bromosuccinimide bromination of the α,β-unsaturated carboxylic acids 1b , 3b , 4b , 5b and 7b is shown to give results entirely analogous to those with the corresponding esters. In this way γ-bromocrotonic acid ( 1 d ), γ-bromotiglic acid ( 3 d ), trans- and cis-γ-bromosenecioic acid ( 7d and 7f ) as well as trans-γ-bromo-Δ^α-pentenoic acid ( 5d ) have been prepared. Iron powder seems to catalyze the lactonization by facilitating both the elimination of methyl bromide (or, less smoothly, hydrogen bromide) and the rotation about the double bond. α-Methyl-Δ^α-butenolide ( 8b ) was converted to 1-benzyl-( 9a ), 1-cyclohexyl-( 9b ), and 1-(4′-picoly1)-3-methyl-Δ^α-pyrrolin-2-one ( 9 c ) by heating at 180° with benzylamine, cyclohexylamine, and 4-picolylamine. The butenolide 8b showed cytostatic and even cytocidal activity; in preliminary tests, no carcinogenicity was observed. Both 8b and 9c exhibited little toxicity.     

Purine nucleoside analogs. 6. Chlorination of acycloguanosine and some of its derivatives with thionyl chloride

The reaction of 9- and 7-(2-hydroyethoxymethyl)guanines and some of their derivatives with thionyl chloride inhexamethylphosphorustriamide was investigated. 9- and 7-(2-Chloroethoxymethyl)- and 8-chloro-, 8-bromo-, and 8-mercapto-9-(2-chloroethoxymethyl)guanines were synthesized. The structure of the compounds was confirmed by the UV and ESR spectra.See [1] for Communication 5.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 671–673, May, 1992.     

Ring transformation of 8-bromo-1,7-phenanthroline in reaction with potassium amide/liquid ammonia

Reaction of 8-bromo-1,7-phenanthroline with potassium amide in liquid ammonia gives besides the corresponding 8-amino compound 2-methyl-1,3,5-triazaphenanthrene. In this ring transformation 7-ethynyl-aminoquinoline-8-aldimine is involved as intermediate, as proved by nmr spectroscopy.