Preparation of 3-bromo-2-methylfuran and 4-bromo-2-methylfuran

4-endo-5-exo-Dibromo-3-methyl-3,6-endo-oxyperhydrophthalic anhydride 3b and 4-exo-5-endo-dibro-mo-3-methyl-3,6-endo-oxyperhydrophtbalic anhydride 3c were isolated from the bromo-adducts of 3-methyl-3,6-endo-oxy-1,2,3,6-tetrahydrophthalic anhydride 2. When 3b or 3c was heated in quinoline, only 3-bromo-2-methylfuran 4 was obtained from 3b and only 4-bromo-2-methylfuran 5 from 3c.     

Preparation andH-NMR spectra of some adamantane derivatives: 2-formyladamantane, 2-bromo-3-methyl-2-homoadamantene, 4,4-adamantylene-1,3-dioxanes and some geminal substitued adamantanes, including 2-adamantylenecyclobutanone

A new two-step synthesis for 2-formyladamantane (3) from adamantanone is described. The Prins reaction of alkylidene-adamantane affords 4,4-adamantylene-1,3-dioxanes (9) and -2-adamantyl-alkanals (10), but no 5,5-adamantylene-1,3-dioxanes. The brominolysis of 2,2-ethyleneadamantane results in 2-bromo-3-methyl-2-homoadamantene (13). No 2,2-carbonsubstituted adamantane derivatives were obtained by reaction of organometallic reagents on adamantyleneoxirane. Grignard reagent may easily open the oxirane moiety by action of magnesium iodide, present in the reaction medium. A one-step synthesis of 2-adamantylenecyclobutanone from adamantanone and difenylsulfonium cyclopropylide is described. Some representative 300 MHz¹H-NMR spectra are given and discussed.     

Synthesis of 2-oxazolone-4-carboxylates from 3-nosyloxy- and 3-bromo-2-ketoesters

New methods for the synthesis of 2-oxazolone-4-carboxylates from 3-nosyloxy- and 3-bromo-2-ketoesters are described. Condensation of 3-nosyloxy-2-ketoesters with methyl carbamate in refluxing toluene in the presence of p-TSA provided 2-oxazolone-4-carboxylates in good yields (41-80%). Alternatively, bromination of alpha-ketoesters with CuBr2 provided 3-bromo-2-ketoesters which condensed with methyl carbamate in the presence of p-TSA and AgOTf under similar conditions to provide 2-oxazolone-4-carboxylates in comparable yields (30-79%). The 2-oxazolone-4-carboxylates bear functionality that can be elaborated to a variety of potentially useful compounds. For example, some of these heterocycles were readily N-acylated, reduced to alcohols, or saponified and coupled with amino acids.     

Chemoselective amination of 5-bromo-2-chloro-3-fluoropyridine

The chemoselective functionalization of 5-bromo-2-chloro-3-fluoropyridine (1c) is described. Catalytic amination conditions (Pd2dba3, Xantphos, base) afford exclusively the bromide substitution product (2) for both secondary amines and primary anilines. A reversal in chemoselectivity is observed under neat conditions in the absence of palladium catalysis, with substitution at the 2-chloro position preferred to generate 3. Last, selective substitution of the 3-fluoro group is achieved under SNAr conditions to afford the dihalo adduct (4).     

Unusual thermal isomerization of 3-bromo-2-ethyltetrahydropyran

3-Bromo-2-ethyltetrahydropyran undergoes isomerization at 230 °C into a 6411 mixture of 7-bromo-4-heptanone and 7-bromo-3-heptanone.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1147–1149, June, 1993.     

Unforeseen formation of 2-bromo-3-hydroxybenzaldehyde by bromination of 3-hydroxybenzaldehyde

Contrary to literature reports, bromination of 3-hydroxybenzaldehyde can afford both 2-bromo-5-hydroxybenzaldehyde and 2-bromo-3-hydroxybenzaldehyde, but 4-bromo-3-hydroxybenzaldehyde was not detected. 2-Bromo-3-hydroxybenzaldehyde was converted into 2-(benzyloxy)-1-bromo-5-methoxy-7-methylnaphthalene. X-ray crystallographic analysis supports the identity of 2-bromo-3-hydroxybenzaldehyde.     

Synthesis of 3-aminomethyl-2-aryl- 8-bromo-6-chlorochromones

[reaction: see text] An efficient synthetic route to Cbz-protected 3-aminomethyl-2-aryl-8-bromo-6-chlorochromones has been developed. 3-Aryl-1-(3-bromo-5-chloro-2-hydroxyphenyl)-2-propen-1-one or 2-aryl-8-bromo-6-chlorochroman-4-one could be reacted under Mannich conditions yielding 2-aryl-8-bromo-6-chloro-3-methylenechroman-4-one, which was further converted to the target compound via an aza-Michael reaction followed by an SeO(2) oxidation. This procedure represents a new method to introduce a primary aminomethyl group at the 3-position of a 2-arylchromone scaffold. The Cbz-protected 3-aminomethyl-2-aryl-8-bromo-6-chlorochromones can, e.g., be used in the synthesis of chromone-based beta-turn peptidomimetics.     

Metalation/functionalization sequences applied to 2-bromo-3-fluoroquinolines

Mono- and disubstituted 2-bromo-3-fluoroquinolines 3 are readily accessible. They can be converted into the 3-fluoroquinoline-2-carboxylic acids 5 by consecutive halogen/metal permutation and into the 2-bromo-3-fluoroquinoline-4-carboxylic acids 6 by consecutive deprotonation and carboxylation. The latter compounds can be reduced to afford the 3-fluoroquinoline-4-carboxylic acids 7. The yields are excellent throughout. Rather than to introduce one functional group alternatively at the 2- or 4-position, one may also attach two different functional groups sequentially to both sites.     

Silica gel-promoted convenient synthesis of 2-bromo-3-hydroxybenzoate derivatives

A convenient silica gel-promoted synthesis of 2-bromo-3-hydroxybenzoate derivatives has been developed via the Diels–Alder reaction of furans with methyl 3-bromopropiolate, followed by a ring-opening aromatization. In addition, 2-bromo-3-methoxybenzoate, derived from 2-bromo-3-hydroxybenzoate with iodomethane, was found to be a good substrate for Pd-catalyzed cross-coupling reactions, despite its sterically hindered structure.     

Reaction of 5-bromo-2, 3′-dipyridyl with magnesium in the presence of ethyl bromide

5-Ethyl-2,3′-dipyridyl was obtained by the reaction of 5-bromo-2,3′-dipyridyl with magnesium in the presence of ethyl bromide. The yield of the Grignard reagent did not exceed 20%.     

Configuration assignment for 3-bromo-2-butenoic acids

Conclusions ¹H and¹³C NMR spectroscopy was used for the reliable determination of the configurations of the E- and Z-isomers of 3-bromo-2-butenoic acids and their esters.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1409–1412, June, 1989.     

Reactions of zinc enolates derived from 1-aryl-2-bromo-2-phenylethanone and 2-bromoindan-1-one with alkyl 2-oxochromene-and 6-bromo-2-oxochromene-3-carboxylates

Zinc enolates derived from 1-aryl-2-bromo-2-phenylethanone react with alkyl 2-oxochromene-3-carboxylates and methyl 6-bromo-2-oxochromene-3-carboxylate to give, respectively, alkyl 4-(2-aryl-2-oxo-1-phenylethyl)-2-oxochroman-3-carboxylates and methyl 6-bromo-4-(2-aryl-2-oxo-1-phenylethyl)-2-oxochroman-3-carboxylate as a single stereoisomer. Zinc enolates derived from 2-bromoindan-1-one react with alkyl 2-oxochromene-3-carboxylates to give alkyl 2-oxo-4-(1-oxoindan-2-yl)chroman-3-carboxylates as a single stereoisomer.     

Reactions of 4,5-Dihydro-5-methyl-3H-spiro[benz-2-azepine-3-cyclohexane] N-Oxide with Some Nucleophilic Reagents

4,5-Dihydro-5-methyl-3H-spiro[benz-2-azepine-3-cyclohexane] N-oxide reacted with cyanide ion and isopropyl magnesium bromide to give the corresponding 1-cyano- and 1-isopropyl-4,5-dihydro-5-methyl-3H-spiro[benz-2-azepine-3-cyclohexane], but reaction with phenyl magnesium bromide, benzyl magnesium chloride, and nitromethane gave cyclic hydroxylamines: 1-substituted N-hydroxy-1,2,4,5-tetrahydro-5-methyl-3H-spiro[benz-2-azepine-3-cyclohexanes] which were oxidized to the corresponding nitrones.     

The addition of methylhypobromite to 4-acetamido-3-bromo-2-pyridone

Bromination of 4-acetamido-3-bromo-2-pyridone in methanol results in the addition of methylhypobromite to the 5,6 double bond of the pyridone.     

1-bromo-1-lithioethene: a practical reagent for the efficient preparation of 2-bromo-1-alken-3-ols

A reliable preparative-scale synthesis of 1-bromo-1-lithioethene is reported. This reagent undergoes clean 1,2-addition with a range of aldehydes and ketones at -105 degrees C to afford the corresponding 2-bromo-1-alken-3-ols in moderate to excellent yield. Efficient diastereoselective addition to alpha-siloxy and alpha-methylcyclohexanones, as well as protected 3-keto furanose sugars, is achieved in the presence of 10 mol % CeBr(3). The resulting bromoallylic alcohol adducts have considerable potential as synthetic building blocks. [reaction: see text]     

Three different dimerizations of 2-bromo-3-methyl-1,4-naphthoquinones

Three types of dimeric naphthoquinones, which possess structurally diverse skeletons, can be prepared in one step from 2-bromo-3-methyl-1,4-naphthoquinones. 2,2'-Dimeric naphthoquinones were prepared by a one-pot Stille-type reaction via vinylstannanes. Oxepines are formed by unexpected domino reactions via 1,4-dihydroxynaphthalene species. Epoxides are formed by a Michael/Darzens reaction via the o-quinone methides.     

An efficient synthesis of 5-bromo-2-methoxy-6-methylaminopyridine-3carboxylic acid

An efficient synthesis of 5-bromo-2-methoxy-6-methylaminopyridine-3-carboxylic acid (1), a carboxylic acid moiety of a potent dopamine D2 and D3 and serotonin-3 (5-HT3) receptors antagonist, (R)-5-bromo-N-(1-ethyl-4-methylhexahydro-1 ,4-diazepin-6-yl)-2-methoxy-6-methylaminopyridine-3-carboxamide, is described. Reaction of methyl 2,6-difluoropyridine-3-carboxylate (12) with methylamine in EtOH at -25 degrees C gave a mixture of methyl 2-fluoro-6-methylaminopyridine-3-carboxylate (13) and the regioisomer 14 in a ratio of 57 : 43. On the other hand, reaction of 12 and methyl 2,6-dichloropyridine-3-carboxylate (16) with sodium methoxide in tetrahydrofuran (THF) and CH2Cl2 provided the 2-methoxypyridine-3-carboxylic esters 20 and 23, respectively, as main products. Similar reaction of 16 in N,N-dimethylformamide (DMF) and MeOH proved to be highly regioselective for the 6-position. A much greater regioselectivity for substitution at the 6-position (>97%) was observed when 16 was treated with 4-methylbenzenethiolate anion in DMF (quantitative yield). After methoxylation of methyl 2-chloro-6-(4-methylbenzenethio)pyridine-3-carboxylate (25b) and successive oxidation of the 6-benzenethio moiety, nucleophilic substitution of the sulfoxide derivative 28 with methylamine gave the 6-methylamino derivative 8. Finally, bromination of 8 and alkaline hydrolysis produced the desired product 1 in an overall yield of 67%.     

Microwave-assisted amination of 3-bromo-2-chloropyridine with various substituted aminoethanols

A simple method for microwave-assisted amination of 3-bromo-2-chloropyridine with various substituted aminoethanols is described. The reaction was carried out under microwave irradiation conditions (at 180 °C for 1-2 h) and the result was superior in terms of conversion and yield when compared to that of the corresponding conventional heating conditions.     

Preparation and fungitoxicity of 3-bromo-6-chloro- and 6-bromo-3-chloro-8-quinolinols

Summary 3-Bromo-6-chloro- and 6-bromo-3-chloro-8-nitro, -8-amino-, and -8-hydroxyquinolines along with 3-bromo- and 3-chloroquinolin-6,8-diols were prepared and tested for antifungal activity against six fungi (Aspergillus niger, A. oryzae, Myrothecium verrucaria, Trichoderma viride, Mucor cirinelloides, Trichophyton mentagrophytes) inSabouraud dextrose broth. Compounds with chlorine in the 3 position were generally more fungitoxic than the corresponding analogues with bromine. 6-Bromo-3-chloro-8-quinolinol inhibited four fungi at levels below 1 µg/ml andA. niger andM. cirinelloides at 2 µg/ml each.

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Synthese und Fungitoxizität von 3-Brom-6-chlor- und 6-Brom-3-chlor-8-chinolinolen

Zusammenfassung 3-Brom-6-chlor- und 6-Brom-3-chlor-8-nitro-, -8-amino- und -8-hydroxychinoline sowie 3-Brom- und 3-Chlorchinolin-6,8-diole wurden hergestellt und gegen sechs Pilzstämme (Aspergillus niger, A. oryzae, Myrothecium verrucaria, Trichoderma viride, Mucor cirinelloides, Trichophyton mentagrophytes) inSabouraud-Dextrosenährmedium auf lhre fungizide Aktivität untersucht. Verbindungen mit Chlor in Position 3 sind durchwegs fungitoxischer als die entsprechenden Bromanalogen. 6-Brom-3-chlor-8-chinolinol hemmt das Wachstum von vier Pilzen bei Konzentrationen unter 1 µg/ml und das vonA. niger undM. cirinelloides bei einer Konzentration von jeweils 2 µg/ml.

     

1-溴-3-甲苯氧基-2-丙醇的Jones试剂氧化反应

本文采用易得的1-溴-3-甲苯氧基-2-丙醇(1a,1b和1c)经Jones试剂氧化反应,合成了1-溴-3-(4-甲基苯氧基)-2-丙酮(2a)、1-溴-3-(3-甲基苯氧基)-2-丙酮(2b)、1-溴-3-(2-甲基苯氧基)-2-丙酮(2c)化合物,并研究了这类反应的副产物。反应中,产物均经硅胶柱分离得到,IR,^1HNMR,MS确定其结构。产物酮(2a)、(2b)、(2c)非常不稳定,影响了元素分析的准确测定。