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.     

Acid-Catalyzed Transformations of 2-(Phenylethynyl)isoborneol

2-(Phenylethynyl)isoborneol was synthesized by treatment of camphor with lithium phenylacetylide. Skeletal rearrangements of the title compound under the Ritter reaction conditions afforded a mixture of N-(4-phenylethynyl- and 4-benzoylmethyl-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)acetamides at a ratio of 8:3. The reaction of 2-(phenylethynyl)isoborneol with formic acid involved mainly Meyer-Schuster rearrangement instead of the expected Rupe rearrangement, and the major product was 2-(1,7,7-trimethylbicyclo[2.2.1]hept-2-ylidene)-1-phenylethanone. The minor product (∼6%) was 1-(2-hydroxy-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)-2-phenylethanone. The Ritter reaction of 2-(1,7,7-trimethylbicyclo[2.2.1]hept-2-ylidene)-1-phenylethanone selectively yielded N-(4-benzoylmethyl-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)acetamide.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 6, 2005, pp. 853–858.Original Russian Text Copyright © 2005 by Koval’skaya, Kozlov, Dikusar.     

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.     

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.     

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.     

Camphor-based alpha-bromo ketones for the asymmetric darzens reaction

(1R)-2-endo-Bromoacetyl-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (endo-2-bromoacetylisoborneol) 4 and its trimethylsilyl ether 3 are presented as efficient reagents for the asymmetric Darzens reaction. From the alpha,beta-epoxy ketone adducts the chiral inductor camphor is removed, by treatment with ceric(IV) ammonium nitrate, to yield the corresponding epoxy acids which are isolated as their dicyclohexylammonium salts.     

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.      

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 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.     

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.     

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.     

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.     

Preparation of fragrant substances from bornyl chloride

Organocuprate reagents were used for introducing bornane (1,7,7-trimethylbicyclo[2.2.1]heptane) moiety into the carbon skeleton of α,β-unsaturated carbonyl compounds. Prospects for use of the products obtained as fragrant substances were assessed.     

The Quantum Yield of Singlet Oxygen in Thermal Degradation of Alcohol Hydrotrioxides

The yield of singlet oxygen (¹О₂) in the decomposition of a number of hydrotrioxides of alcohols (cyclobutanol, cyclopentanol, cyclohexanol, cycloheptanol, cyclooctanol, L-menthol, 1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol, 1,3,3-trimethylbicyclo[2.2.1]heptan-2-ol, heptan-4-ol, propanol-2, and 1-cyclopropylethanol) has been determined using the IR chemiluminescence technique. It has been shown that cyclopentanol, 1,3,3-trimethylbicyclo[2.2.1]heptan-2-ol and 1-cyclopropylethanol hydrotrioxides are efficient sources of singlet oxygen; the yield of ¹О₂ reaches up to 58%.     

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.     

1,7,7-三甲基双环[2.2.1]庚基羟烷基醚的合成

酸催化莰烯与二醇的羟烷氧基化反应是合成标题化合物的可行路线。前人所用酸性催化剂有离子交换树脂及路易斯酸 BF_3·Et_2O。松原义治等报道用离子交换树脂催化茨烯或三环烯分别与乙二醇、1,2-丙二醇反应获得相应的醚,醚化产率分别为42%、33%。Fujioka,Futoshi 等以 BF_3·Et_2O 为催化剂,使莰烯与1,3-丁二醇反应获得产率为34%的醚。迄     

Camphor-based α-bromoketones for the asymmetric darzens reaction: Insights into the mechanism using density functional theory

Density functional theory (DFT) calculations at B3LYP/6-31G(d,p) level were carried out to investigate the mechanism of the reaction of benzaldehyde (BA) or acetaldehyde (AD) with (1R)-2-endo-bromoacetyl-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (endo-2-bromoacetylisoborneol) 1 (Scheme 1). The calculations indicate that the reactions are diastereoselective, in good agreement with the experimental results [1]. Moreover, the calculations show that these reactions proceed via two steps: (1) an aldol-like reaction and (2) the formation of an epoxide. Our calculation study of the transition states demonstrates that the terminal hydroxyl group in compound 1 is vital for the stereoselectivity of the reactions.     

新的手性β-亚磺酰亲双烯体用于不对称Diels-Alder反应

手征性cis-β-亚磺酰丙烯酸酯可从(1R, 2S, 3R)-3-巯基-1,7,7-三甲基二环[2.2.1]庚-2-醇制备, 它与环戊二烯的反应得Diels-Alder加成物, 并具有相当高的端基差向异构选择性。     

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%).     

Palladium Complex of Camphor-Substituted Tetrapyrazinoporphyrazine as a Stationary Phase of Gas Chromatography

Russian Journal of General Chemistry - Surface modification of the diatomite adsorbent Hezasorb AW-HMDS by tetra(1,7,7-trimethylbicyclo[2.2.1]heptane[2,3-b]pyrazino)porphyrazine Pd(II) was...