Synthesis and Dehydration of endo-2-(3-R-Isoxazol-5-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-exo-2-ols

endo-2-Ethynyl-1,7,7-trimethylbicyclo[2.2.1]heptan-exo-2-ol reacts with nitrile oxides, yielding endo-2-(3-R-isoxazol-5-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-exo-2-ols. Treatment of the latter with methanesulfonyl chloride in pyridine leads to dehydration and formation of mixtures of the corresponding 1-(3-R-isoxazol-5-yl)-3,3-dimethyl-2-methylenebicyclo[2.2.1]heptanes and 2-(3-R-isoxazol-5-yl)-1,7,7-trimethylbicyclo[2.2.1]hept-2-enes at a ratio of 2:1.     

Synthesis of chiral benzoacridinone derivatives by three-component condensation of [(1<Emphasis Type="Italic">S</Emphasis>,4<Emphasis Type="Italic">S</Emphasis>)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylidene]acetaldehyde with naphthalen-1-amine and cyclic β-diketones

Three-component condensation of [(1S,4S)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylidene]acetaldehyde with naphthalen-1-amine and cyclic β-diketones gave 7-[(1S,4S)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylidenemethyl]-7,8,9,10,11,12-hexahydro-7H-benzo[c]acridin-8-one derivatives possessing three or more asymmetric carbon atoms. Steric factors were found to be responsible for the predominant formation of the (7R)-isomers (R/S ≈ 7: 5) and orientation of substituents in the cyclohexenone fragment. The same factors determined complete regioselectivity of the reaction with methyl 2,4-dioxocyclohexane-1-carboxylates as dicarbonyl component, which led to exclusive formation of methyl 8-oxobenzoacridine-11-carboxylates. In the reaction of [(1S,4S)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylidene]acetaldehyde with naphthalen-1-amine and barbituric acid as dicarbonyl component, the only product was that formed by two-component condensation of barbituric acid with bicyclic aldehyde.     

Isocamphanone in synthesis of 3-alkyl- and 6-alkyl-substituted camphor derivatives

On the interaction of isocamphanone with butyllithium, 2-butyl-5,5,6-trimethylbicyclo[2.2.1]heptan-endo-2-ol is formed stereospecifically. As a result of skeletal rearrangements of carbonium ions taking place in the course of the reaction, the Ritter reaction of this tertiary alcohol with acetonitrile and benzonitrile has given endo-3-butyl-1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-ylacylamines and endo-6-butyl-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylacylamines.Institute of Physical Organic Chemistry, Academy of Sciences of the Belorussian SSR, Minsk. Translated from Khimiya Prirodynkh Soedinenii, No. 6, pp. 807–812, November–December, 1988.     

Isocamphanone in synthesis of 3-alkyl- and 6-alkyl-substituted camphor derivatives

On the interaction of isocamphanone with butyllithium, 2-butyl-5,5,6-trimethylbicyclo[2.2.1]heptan-endo-2-ol is formed stereospecifically. As a result of skeletal rearrangements of carbonium ions taking place in the course of the reaction, the Ritter reaction of this tertiary alcohol with acetonitrile and benzonitrile has given endo-3-butyl-1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-ylacylamines and endo-6-butyl-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylacylamines. Institute of Physical Organic Chemistry, Academy of Sciences of the Belorussian SSR, Minsk. Translated from Khimiya Prirodynkh Soedinenii, No. 6, pp. 807–812, November–December, 1988.     

Synthesis,structural chemistry and antimicrobial activity of −(−) borneol derivative

Borneol is a monoterpene that is a part of traditional Chinese and Japanese medicine. (−) borneol reacted with methanesulfonyl chloride in THF/pyridine to afford the new 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl methane sulfonate derivative in excellent yield. The product is characterized by H1NMR, C¹³NMR, mass spectroscopy as well as elemental analysis and its structure was identified by X-ray single crystal diffraction. The packing of 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl methanesulfonate exhibits the non-classical C-H···O hydrogen bonding in C(4) and R² ₂(8) chain and ring motifs as structural determinants. This was also confirmed by the analysis of Hirshfeld surfaces. The 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl methane sulfonate antimicrobial activity was tested and compared with its parent (−) borneol against three different pathogens. Particularly, 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl methane sulfonate showed high sensitivity, compared to Chloramphenicol reference material, against Escherichia coli.      

Synthesis and molecular structure of di(4-hydroxy-2,6-diisoborn-2-ylphenyl)methane

Di(4-hydroxy-2-{(1R*,2S*,4S*)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl}-6-{(1S*,2R*,4R*)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl})methane was synthesized by condensation of the meso-diastereomer of 2,6-diisobornylphenol with paraformaldehyde under acid catalysis. The product structure as a meso-forms was confirmed by XRD analysis.     

1-(3,5-二甲基苯基)-1-[(1S,4S)-1,7,7-三甲基双环[2.2.1]庚烷-2-基]肼的合成工艺改进

以3,5-二甲基苯胺和2-莰酮为起始原料,在微波促进下,经缩合反应制得N-(3,5-二甲基苯基)-1-(1S,4S)-1,7,7-三甲基二环[2.2.1]庚烷-2-亚胺(1);1经硼氢化钠还原后再与羟胺-O-磺酸经胺化反应合成了1-(3,5-二甲基苯基)-1-[(1S,4S)-1,7,7-三甲基双环[2.2.1]庚烷-2-基]肼,总收率70.4%,其结构经1H NMR和ESI-MS确证。     

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.     

Tandem molecular rearrangement in the alkylation of phenol with camphene

The alkylation of phenol with camphene in the presence of boron trifluoride in glacial acetic acid was accompanied by tandem molecular rearrangement with formation of a mixture of ortho- and para-substituted phenols having 1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yl and 5,5,6-trimethylbicyclo[2.2.1]hept-exo-2-yl substituents. The same products were obtained by rearrangement of 1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yloxybenzene under analogous conditions. Similar reactions performed in the presence of aluminum phenoxide as catalyst resulted in predominant formation of the corresponding ortho-substituted phenols.     

Interesting Transformations of Thiocamphor

Thiocamphor has been found to furnish bornane, camphor, isoborneol, isobornylthiol, bornylthiol, tetrahydro-bis-(1,7,7-trimethylbicyclo[2.2.1]heptyl)-3,3′-disulfide, and three isomeric bis-(1,7,7-trimethylbicyclo[2.2.1]heptyl)-3,3′-dithiols when treated with NaBH₄ either in dry THF or dry diethylene glycol diethyl ether. The origins of the above interesting compounds and their mass spectral characterization are presented in this article.     

Synthesis of certain 1,7,7-trimethyl-bicyclo[2.2.1]heptane derivatives with anticonvulsant, hypoglycemic and anti-inflammatory potential

Starting from (1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylideneamino)-acetic acid methyl esters 6a, 6b, the aryl esters of exo-2-[methyl-(1,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl)-amino]-ethanol (10a-f) and exo-2-[methyl-(1,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl)-amino-2-phenyl-ethanol (10g-n) are prepared. Also, from the reaction of 1,7,7-trimethyl-bicyclo[2.2.1]heptan nitramine 4 with either 2-amino-1-(4-nitrophenyl)-propane-1,3-diol (17) or 1-aminomethyl-cyclohexanol (18), the alcohol exo-1-[(1,7,7-trimethyl-bicylo[2.2.1]hept-2-ylamino)-methyl]-cyclohexanol (13), exo-1-(4-aminophenyl)-2-(1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylamino)-propane-1,3-diol (14) and 1-(4-aminophenyl)-2-[methyl-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]-amino]-propane-1,3-diol (16) are synthesized. At a dose level of 12.5 mg/kg, compounds 16 and 14 show a significant anticonvulsant protection against pentylenetetrazole seizures (100% and 83% protection, respectively) compared with diphenylhydantoin sodium (50 mg/kg, 100%) and deramciclane fumarate (25 mg/kg, 83%), used as reference drugs. Compound 10b at dose level of 50 mg/kg displayed 41%, hypoglycemic activity, compared with gliclazide (10 mg/kg, 23%) as reference drug. Furthermore, the prepared compounds are screened for their anti-inflammatory potential at a dose level of 50 mg/kg. Compounds 10i, 10g, 14 and 10m exhibited 92%, 90%, 88% and 80% inhibition in rat paw weight, respectively, with no sign of ulcerogenicity, compared with indomethecin (5 mg/kg, 81%).     

Reaction of 1,7,7-trimethylbicyclo[2.2.1]heptane-2,3-dione with hexaethyltriamidophosphite in the presence of diethylammonium chloride. Synthesis and the three-dimensional structure of (1,7,7-trimethyl-2-oxobicyclo[2.2.1]hept-3-yloxy)tris(diethylamino)phosphonium chloride

The reaction of 1,7,7-trimethylbicyclo[2.2.1]heptane-2,3-dione with hexaethyltriamido-phosphite in the presence of diethylammonium chloride afforded a stable quasiphosphonium salt, viz., (1,7,7-trimethyl-2-oxobicyclo[2.2.1]hept-3-yloxy)tris(diethylamino)phosphonium chloride, as one diastereomer (racemate, 1R*,3S*,4S*). Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 383–385, February, 2006.     

Specificity of the reaction of (−)-1-{(1S,2R,4R)-1-ethenyl-2-hydroxy-7,7-dimethylbicyclo[2.2.1]hept-2-yl}xethanone with ethenylmagnesium bromide

Ethenylmagnesium bromide (1.5 equiv) forms a chelate with (?)-1-{(1S,2R,4R)-1-ethenyl-2-hydroxy-7,7-dimethylbicyclo[2.2.1]hept-2-yl} ethanone in THF and promotes its fast primary α-ketol rearrangement into 1-ethenyl-2-hydroxy-2,8,8-trimethylbicyclo[3.2.1]octan-3-one. The latter reacts with excess magnesium reagent (0.5 equiv) according to common 1,2-addition pattern at the carbonyl group and is simultaneously involved in the second α-ketol rearrangement which leads to 1-ethenyl-3-hydroxy-3,8,8-trimethylbicyclo[3.2.1]octan-2-one as thermodynamically more stable regioisomer.     

Reductions of (1R,3R,4R)-3-([1,2,4]triazolo[4,3-x]azin-3-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones and their analogues

Reductions of (1R,3R,4R)-3-([1,2,4]triazolo[4,3-x]azin-3-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones and their lactone analogues, prepared from (1R)-(+)-camphor, were studied. Catalytic hydrogenation selectively led to partial saturation of the [1,2,4]triazolo[4,3-x]azine residue, while in reactions with borane–methylsulfide coordination of borane to the 1-position of [1,2,4]triazolo[4,3-x]azine system took place. On the other hand, activation of the carbonyl group in (1R,3R,4R)-3-([1,2,4]triazolo[4,3-x]azin-3-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones with boron trifluoride etherate followed by reaction with borane–methylsulfide furnished the corresponding isoborneols, stereoselectively. The structures of all representative compounds were confirmed by X-ray diffraction.     

Heteropolyacids as new catalysts of the Ritter reaction

Some nitriles reacted with camphene in the presence of heteropolyacids (H₃PW₁₂O₄₀, H₄SiW₁₂O₄₀, H₇PMo₁₂O₄₀) as catalyst to give N-(1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)-substituted amides in fairly high yields.     

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.     

A Convenient Stereoselective Synthesis of (1R,2S,3R,4S)-3-(Neopentyloxy)isoborneol

A convenient preparation of (1R,2S,3R,4S)-3-(neopentyloxy)isoborneol (= (1R,2S,3R,4S)-3-(2,2-dimethyl-propoxy)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol; 1a ), a valuable chiral auxiliary, is described. The synthesis involves six steps starting from the readily available camphorquinone ( 5 ) and gives 1a in 48% overall yield. The key step is the chemoselective hydrolysis of the less hindered 1,3-dioxolane moiety in the camphorquinone di-acetal 4 .     

Design of Schiff base-like postmetallocene catalytic systems for polymerization of olefins: IX. Synthesis of salicylaldehydes containing an isobornyl substituent and hydroxyphenyl imine ligands based thereon

Reactions of substituted 2-(1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yl)phenols with paraformaldehyde in the presence of tin(IV) chloride and 2,6-dimethylpyridine gave the corresponding salicylaldehydes which reacted with primary amines to produce a series of new Schiff bases as ligands for complex formation with transition metals.     

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.     

A class II aldolase mimic

[structures: see text] A class II aldolase-mimicking synthetic polymer was prepared by the molecular imprinting of a complex of cobalt (II) ion and either (1S,3S,4S)-3-benzoyl-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one (4a) or (1R,3R,4R)-3-benzoyl-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one (4b) in a 4-vinylpyridine-styrene-divinylbenzene copolymer. Evidence for the formation of interactions between the functional monomer and the template was obtained from NMR and VIS titration studies. The polymers imprinted with the template demonstrated enantioselective recognition of the corresponding template structure, and induced a 55-fold enhancement of the rate of reaction of camphor (1) with benzaldehyde (2), relative to the solution reactions, and were also compared to reactions with a series of reference polymers. Substrate chirality was observed to influence reaction rate, and the reaction could be competitively inhibited by dibenzoylmethane (6). Collectively, the results presented provide the first example of the use of enantioselective molecularly imprinted polymers for the catalysis of carbon-carbon bond formation.