Reaction of 2-Methylenenorbornane with N-Bromosuccinimide

The reaction of 2-methylenenorbornane with N-bromosuccinimide produced a mixture of six monobromides in an overall yield of about 60%. By irradiation in the presence of benzoyl peroxide exo- and endo-3-bromo-2-methylenenorbornanes, 2-bromomethylnorborn-2-ene, Z- and E-2-bromomethylenenorbornanes and 1-bromomethylnortricyclene were found in a percentage ratio of 43.0, 7.5, 6.5, 19.0, 19.0 and 5.0. Without benzoyl peroxide, in the dark, the same products were obtained, but in a percentage ratio of 23.0, 3.0, 17.0, 26.0, 26.0 and 7.0. These results are rationalized in terms of an ionic mechanism in concurrence with some radical mechanism contribution.     

Additions to bicyclic olefins—X: Stereochemistry of the oxymercuration-demercuration of cis-bicyclo[3.3.0]oct-2-ene,endo-trimethylene-norborn-8-ene and related olefins

The stereochemistry of the oxymercuration-demercurarion (OM-DM) of olefins related to the cis-bicyclo(3.3.0]octane and endo-2,3-trimethylenenorboniane structures was determined. In the case of cis-bicyclo(3.3.0]oct-2-ene, hydration occurs preferentially at the less hindered 3-position, with little preference shown for exo vs endo. The more hindered 2-product shows a 11:1 preference for the exo-product. The presence of Me groups at positions 2- or 3-, results in the formation of the tertiary alcohols with approximately a 4:1 favoring of the exo-isomer. (The oxymercuration intermediate exhibits a rapid equilibration with time. Consequently, the 4:1 ratios may not represent the true limit for the isomer distribution in the initial kinetic product.) Similarly, 2-methylenebicyclo[3.3.0]octane reveals an 8:1 preferential formation of the exo-alcohol. In the case of endo-trimethylene-norborn-8-ene, the oxymercuration stage is extraordinarily slow and the results do not fit this pattern. Possibly the very slow oxymercuration stage permits equilibration of the initial reaction product. On the other hand, the reaction is fast with 8-methylene-endo-trimethylenenorbornane and the product is 100% of the tertiary exo-alcohol. The same behavior is observed for 2-methylenenorbornane. Surprisingly, 2-methylene-endo-trimethy-lenenorbornane fails to undergo oxymercuration. Consequently, both endo-trimethylenenorborn-8-ene and 2-methylene-endo-trimethylenenorbornane exhibit an exceptional inertness toward oxymercuration, presumably related to the highly rigid U-shaped structure of the parent system.     

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.     

Zur Photodimerisierung von 3-Phenyl-2H-azirinen. Vorläufige Mitteilung

Irradiation of 3-phenyl-2H-azirine ( 2 ) in benzene solution with a high-pressure mercury lamp yields 4,5-diphenyl-1,3-diazabicyclo[3,1,0]hex-3-ene ( 4 ) and not 3-phenylimino-4-phenyl-1-azabicyclo[2,1,0]pentane ( 1 ), as had been reported previously by others [2]. 2-Methyl-3-phenyl-2H-azirine ( 3 ) yields on irradiation a 2:1 mixture of 2-exo, 6-exo- and 2-exdo, 6-exo-dimethyl-4,5-diphenyl-1,3-diazabicyclo[3,1,0]hex-3-ene (2-exo,6-exo- and 2-endo, 6-exo- 5 ). Irradiation of 2,3-diphenyl-2H-azirine ( 8 ) leads to the formation of 2,4,5-triphenyl-imidazole ( 9 ) and tetra-phenylpyrazine ( 10 ). The suggested reaction path for the generation of 9 and 10 is shown in Scheme 2.     

Synthesis of 1-{4a,6-dimethyl-4a,9a-dihydropyrano-[3,4-<Emphasis Type="Italic">b</Emphasis>]indol-9(1<Emphasis Type="Italic">H</Emphasis>)-yl}ethanone

Heating of the bromination product of 4-methyl-3,6-dihydro-2H-pyran with 4-toluidine or 2-bromo-4-methylamiline in triethylamine gave 4-methyl-N-(4-methylphenyl)- and N-(2-bromo-4-methylphenyl)-4-methyl-3,6-dihydro-2H-pyran-3-amines which were converted into the corresponding amides by reaction with bromo- or chloroacetyl chloride. 1-{4a,6-Dimethyl-4a,9a-dihydropyrano[3,4-b]indol-9(1H)-yl} ethanone was synthesized in good yield by heating N-(2-bromo-4-methylphenyl)-N-(4-methyl-3,6-dihydro-2Hpyran-3-yl)acetamide in boiling toluene in the presence of palladium(II) acetate, triphenylphosphine, copper(II) acetate, triethylamine, and potassium carbonate.     

Low-Temperature Reactions of α-Bromopropanoyl Chloride with Lithium Derivative of Ethyl Acetate

The reaction of 2-bromopropanoyl chloride with lithium ethyl acetate generated in situ by the reaction of equimolar amounts of lithium diisopropylamide with ethyl acetate forms, depending on the conditions (temperature, time, reagent ratio), diethyl 2,2′-(3-methyloxirane-2,2-diyl)diacetate, 2,2-dibromo-N,N-diisopropylpropanamide, and ethyl (5-methyl-4-oxo-4,5-dihydrofuran-2-yl)acetate as minor by-products along with the expected acylation product ethyl 4-bromo-3-oxopentanoate. The reaction with 2 or 5 equiv of lithium ethyl acetate (–78°C → –20°C) gave, together with the mentioned α-bromo ester, ethyl (5-methyl-4-oxo-4,5-dihydrofuran-2-yl)acetate formed as a result of transformations of the adduct of the second LiCH₂CO₂Et molecule and ethyl-4-bromo-3-oxopentanoate. The reaction 2-bromopropanoyl chloride with sodium malonic ester involves acylation of enol form of the primary expected acylation product to afford dimethyl |2-bromo-1-[(2-bromopropanoyl)oxy]propylidene-malonate.

     

Hetero-Diels-Alder Additions of α,β-Unsaturated-Acyl Cyanides. Part 3. Syntheses of 3-bromo-2-ethoxy-3,4-dihydro-2H-pyran-6-carbonitriles,and about their transformation to 2-ethoxy-2H-pyrans

Cycloadditions of the α,β-unsaturated-acyl cyanides 1–3 with (Z)-or (E)-1-bromo-2-ethoxyethene ( 4 ) may be performed at moderate temperatures and provide in good yields the 3-bromo-2-ethoxy-3,4-dihydro-2H-pyran-6-carbonitriles 5–7 , respectively (Scheme 1). Diastereoisomeric pairs of products result at room temperature merely from the ‘endo’- and ‘exo’-transition states; more complex mixtures appear above 60° as a consequence of (Z)/(E)-isomerization of 4 . The relative stability of the anomers of 5 and 6 is explored by treatment with BF₃·Et₂O. Acid alcoholysis (MeOH or EtOH) of 5 leads to acetals 9a , b of 4-bromo-5-oxopentanoate. Alkyl (2Z,4E)-5-ethoxypenta-2,4-dienoates 12 , 17 , and 20 , are formed in alcoholic alkoxide solutions from 5 , 6 , and 7 , respectively, which is compatible with the intermediacy of 2-alkoxy-2H-pyrans and their valence tautomers, α,β-unsaturatedacyl cyanides. Methoxide addition to the CN group competes with dehydrobromination in case of 5 ; it leads to 3-bromo-3,4-dihydro-2H-pyran-6-carboximidate 13 (ca. 50% at ?20°) which can be hydrolyzed to the methyl carboxylate 14 . DBU (1,8-diazabicyclo[5,4,0]undec-7-ene) in benzene converts 5 to 6-ethoxy-2-oxohexa-3,5-dienenitrile ( 11 ), the ring-opening product of an obviously unstable 2-ethoxy-2H-pyran; the same reagent dehydrobrominates 6 to 2-ethoxy-4-methyl-2H-pyran-6-carbonitrile ( 15 ). HBr Elimination from 7 takes place with great ease in presence of pyridine, or even during chromatography on alumina, and leads to the stable ethyl 6-cyano-2-ethoxy-2H-pyran-4-carboxylate ( 18 ); this dimerizes at room temperature to give a 1:3 mixture of tricyclic adducts ‘endo’- 21 and ‘exo’- 21 . The structure of the latter is established by an X-ray crystallographic analysis.     

Addition of bromine to 2-methyl-2-azabicyclo[2.2.1]hept-5-ene

Addition of bromine to 2-methyl-2-azabicyclo[2.2.1]hept-5-ene was studied. Unexpectedly, 3-bromo-1-methyl-1-azoniatricyclo[2.2.1.0^2,6]heptane tribromide was isolated rather than the product of bromine addition to the double bond. The former reacted with the starting alkene in a polar solvent to form the corresponding monobromide.     

Evidence for a synfacial nucleophilic displacement with allylic rearrangement. Mechanistic conclusions. Preliminary communication

Reduction of exo-2-methyl-3, 4-dichlorobicyclo[3.2.1]oct-2-ene and the exo-2-phenyl-3,4-dibromo analogue with lithium aluminium hydride proceeds mainly with allylic rearrangement. Moreover, hydride enters and bromide leaves synfacially. The stereochemistry of the process is discussed in the light of the favourable energy of a quasi-cyclic transition state in which reagent and halide are complexed.     

Reinvestigation of the synthesis of 5-arylamino-2-picolines

Reaction of 5-bromo- or 3-bromo-2-methylpyridine with o-nitroaniline gave the corresponding N-[2-methyl-5(or 3)pyridyl]-o-nitroanilines. Reduction to the corresponding amino derivatives and ring closure to 1-[2-methyl-5(or 3)pyridyl]benzotriazole allowed the structures to be confirmed and an earlier literature report to be corrected. Displacement of bromide by anthranilic acid from 5-bromo-2-methylpyridine and decarboxylation gave N-(2-methyl-5-pyridyl)aniline.     

Natural product chemistry,Part 132: Synthesis and oxidative cyclisation of 1,3-dihydroxy-10-methyl-4-(3-methylbut-2-enyl)-9(10H)-acridinone (glycocitrine-II)

Summary Reaction of 1,3-dihydroxy-10-methyl-9(10H)-acridinone (1) and 1-bromo-3-methylbut-2-ene (mol. ratio 1:1) in tetrahydrofuran at 20°C in the presence of alumina gave prenylacidinones2 (glycocitrine-II) and8 and the diprenylacridinone9; with an excess of 1-bromo-3-methylbut-2-ene, the prenyldihydropyranoacridinones12 and13 were formed. Oxidation of glycocitrine-II (2) withm-chloroperbenzoic acid furnished the furanoacridinone5 and the pyranoacridinone6; dehydration of the latter compound gave noracronycine (10).(the late)     

Reactions of <Emphasis Type="Italic">N</Emphasis>-and <Emphasis Type="Italic">C</Emphasis>-Alkenylanilines: VII. Synthesis of Indole Heterocycles from Products of Reaction between <Emphasis Type="Italic">N</Emphasis>-Mesyl-2-(1-alken-1-yl)anilines and Halogens

N-Mesyl-2-(1-methyl-1-butenyl)-6-methylaniline reacted with Br₂ to afford N-mesyl-2-(3-bromo-1-penten-2-yl)aniline that under treatment with NH₃ or amines underwent cyclization into N-mesyl-7-methyl-3-methylene-2-ethylindoline. The reaction of N-mesyl-2-(1-methyl-1-buten-1-yl)-4-methyl- and 2-(1-methyl-1-buten-1-yl)aniline with Br₂ gave rise to the corresponding N-mesyl-2-(2-bromo-1-methyl-1-buten-1-yl)anilines. Under the similar conditions N-tosyl-2-(1-cyclohexen-1-yl)aniline was converted into N-tosyl-2-(6-bromo-1-cyclohexen-1-yl)aniline that under treatment with NH₃ furnished N-tosyl-1,2,3,9a-tetrahydrocarbazole. The reaction of N-mesyl-1,2,3,9a-tetrahydrocarbazole with CuBr₂ in MeOH afforded N-mesyl-4-methoxy-1,2,3,4-tetrahydrocarbazole. N-Mesyl-6-methyl-2-(1-cyclopenten-1-yl)aniline in reaction with Br₂ in the presence of NaHCO₃ was oxidized into the corresponding cyclopentenone, and with NBS it gave N-mesyl-2-(2-bromo-1-cyclopenten-1-yl)aniline.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 5, 2005, pp. 730–737.Original Russian Text Copyright © 2005 by Gataullin, Sotnikov, Spirikhin, Abdrakhmanov.     

The Homoconjugated Electron-Releasing Carbonyl Group of 1-Methylbicyclo[2.2.1]hept-5-en-2-one. Regioselective syntheses of 5-chloro- and 6-chloro-1-methylbicyclo[2.2.1]hept-5-en-2-one

Syntheses of (±)-2-exo-cyano-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl acetate ( 1 ) and of (±)-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 2 ) are reported. The additon of PhSeCl to 1 afforded (±)-5-endo-chloro-2-exo-cyano-1-methyl-6-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]hept-2-endo-yl acetate ( 6 ), whereas 2 added to PhSeCl with the opposite regioselectivity giving (±)-6-endo-chloro-1-methyl-5-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]heptan-2-one ( 7 ). These adducts were converted into 5-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 9 ) and 6-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 10 ), respectively.     

Pyrimidine derivatives XII. A convenient preparation of 6-formylpyrimidinedione and 2- and 3-formylpyridine derivatives from corresponding nitrooxymethyl derivatives

The convenient preparation of 6-fomylpyrimidinedione derivatives and 2- and 3-formylpyridine are described. Thus, 5-bromo-1,3-dimethyl- ( 1a ), 5-bromo-3-methyl-1-(2-nitrooxyethyl)- ( 1b ), and 5-bromo-3-methyl-1-(3-nitrooxypropyl)-2,4(1H,3H)-pyrimidine-dione ( 1c ) were converted to the corresponding 6-formyl compounds 2a, 2b , and 2c , respectively, in excellent yields by the reaction with triethylamine and 1,4-diazabicyclo[2.2.2]octane. These 6-formylpyrimidinedione derivatives are key intermediates for the preparation of 6-carbon-carbon substituted compounds, which are expected to be potential antitumor and antiviral agents. Similarly, 2-(and 3-)formylpyridine ( 9a (and 9b )) were obtained by the reaction of 2-(and 3)nitrooxymethylpyridine ( 8a (and 8b )) with 1,4-diazabicyclo[2.2.2]octane.     

Sterical Hindrances as a Driving Force of Skeleton Rearrangements of Fenchone and Its Oxime in Ritter Reaction

Fenchone (1,3,3-trimethylbicyclo[2.2.1]heptan-2-one) in reaction with acetonitrile in the presence of sulfuric acid (Ritter reaction) due to steric hindrances preventing geminal addition of two nucleophile molecules gives rise to a mixture of 1,2-exo-diacetamido-6-endo,7,7-trimethylbicyclo[2.2.1]heptane, 2-endo6-exo-diacetamido-3,3,6-trimethylbicyclo[2.2.1]heptane, and 2-exo,6-exo-diacetamido-1,3,3-tri- methylbicyclo[2.2.1]heptane in the ratio of 6:4:1. Fenchone oxime under condition of this reaction affords a mixture of stereoisomeric cis- and trans-acetamido-1-methyl-3-(-cyanoisopropyl)cyclopentanes in 2:3 ratio.     

Synthesis and Ritter Reaction of 3-exo-Hydroxymethyl-5,5,6-trimethylbicyclo[2.2.1]heptan-2-one

3-exo-Hydroxymethyl-5,5,6-trimethylbicyclo[2.2.1]heptan-2-one was prepared by treatment of isocamphanone with Paraform in the presence of alkali in DMF. The product reacts with acetonitrile in the presence of sulfuric acid (Ritter reaction) to form a mixture of 2-(acetylamino)-3-(acetylaminomethyl)-5,5,6-trimethylbicyclo[2.2.1]hept-2-ene and 2,2-bis(acetylamino)-3-(acetylaminomethyl)-5,5,6-trimethylbicyclo[2.2.1]heptane in a 1:1 ratio. Attempted hydroxymethylation of isocamphanone in DMSO gave bis(isocamphanon-3-endo-yl)methane.     

Acylderivate von 2-Amino-p-pyrrolinen

Zusammenfassung Die Acylierung von 2-Amino-3.3-diphenyl-5-methyl-1-pyrrolin (1) und 2-Amino-3.3-diphenyl-1-pyrrolin (2) erfolgt in den hier untersuchten Fällen am N-2-(exo)-Stickstoff. Die Umsetzung der cyclischen Amidine1 und2 mit BrCN gibt jedoch neben den N-2-(exo)-auch die N-1-(endo)-Cyanamidine. Diese werden in die entsprechenden Carbamoyl- und Thiocarbamoylamidine umgewandelt.

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Acylderivatives of 2-amino-1-pyrrolines

Acylations of 2-amino-3.3-diphenyl-5-methyl-1-pyrroline (1) and 2-amino-3.3-diphenyl-1-pyrroline (2) occur at the N-2-(exo)-nitrogen. However, reaction of1 and2 with BrCN yields not only the N-2-(exo)-cyanoamidines but also the N-1-(endo)-isomers. Either is converted into the corresponding carbamoyl and thiocarbamoyl amidines.

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3. Mitt.:W. Klötzer undB. Schmidt, Mh. Chem.102, 180 (1971).

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Teile dieser Arbeit sind Gegenstand von Patentanmeldungen.     

Derivatives of exo-5-Aminomethyl-endo-5-methylbicyclo[2.2.1]hept-2-ene and exo-5-Aminomethyl-endo-5-methyl-exo-2,3-epoxybicyclo[2.2.1]heptane

exo-5-Aminomethyl-endo-5-methylbicyclo[2.2.1]hept-2-ene and its 2,3-epoxy derivative were synthesized, and their geometric parameters and conformational properties, in particular the barriers to rotation of the aminomethyl fragment about the exocyclic C⁵ÄC bond, were studied by the molecular-mechanics method (MMX) and compared with those found for structurally related exo-5-aminomethylbicyclo[2.2.1]hept-2-ene. The title compounds were brought into reactions with electrophilic reagents: arenesulfonyl chlorides, isocyanates, and isothiocyanates.     

Reaction of (2-Nitro- and 2-Bromo-2-nitroethenyl)phosphonates with 1,3-Cyclohexadiene

Specific features of the reactions of bis(chloroethyl) 2-nitro- and 2-bromo-2-nitroethenylphosphonates with 1,3-cyclohexadiene were studied. It was found that the reaction with 2-nitroethenylphosphonate occurs stereoselectively and provides bis(2-chloroethyl) endo-(3-nitrobicyclo[2.2.2]oct-5-en-2-yl)phosphonate. 2-Bromo-2-nitroethenylphosphonate under the same conditions gives a mixture of the endo and exo isomers of the corresponding nitrobicyclooctenes. Enhanced tendency of adducts derived from gem-bromonitroethenyl-phosphonates for intramolecular transformations, such as dehydrohalogenation and aromatization, under the cycloaddition conditions was revealed.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 7, 2005, pp. 1106–1110.Original Russian Text Copyright © 2005 by Anisimova, Kuzhaeva, Berkova, Deiko, Berestovitskaya.     

Amine-induced rearrangements of 2-bromo-1-(1H-indol-3-yl)-2-methyl-1-propanones: A new route to α-substituted indole-3-acetamides, β-substituted tryptamines, α-substituted indole-3-acetic acids and indole β-aminoketones

The reaction of 2-bromo-1-(1H-indol-3-yl)-2-methyl-1-propanone ( 1 ) and 2-bromo-1-(1-methyl-1H-indol-3-yl)-2-methyl-1-propanone ( 2 ) with primary amines proceeds in good yields to produce rearranged amides by a proposed pseudo-Favorskii mechanism. These amides in turn can either be reduced to produce β-substituted tryptamines or hydrolyzed to produce substituted indole-3-acetic acids. When the reaction is carried out using bulky primary or secondary amines, β-aminoketones are produced by elimination of hydrogen bromide followed by Michael addition. When hindered secondary amines or tertiary amines are used, elimination to the α,β-unsaturated ketones occurs.