- Non-conventional methodologies in the synthesis of 1-indanones
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1-Indanones have been successfully prepared by means of three different non-conventional techniques, namely microwaves, high-intensity ultrasound and a Q-tube reactor. A library of differently substituted 1-indanones has been prepared via one-pot intramolecular Friedel-Crafts acylation and their efficiency and "greenness" have been compared.
- Oliverio, Manuela,Nardi, Monica,Costanzo, Paola,Cariati, Luca,Cravotto, Giancarlo,Giofre, Salvatore Vincenzo,Procopio, Antonio
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p. 5599 - 5610
(2014/06/10)
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- SUBSTITUTED FLUOROETHYL UREAS AS ALPHA 2 ADRENERGIC AGENTS
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Therapeutic compounds, and methods, compositions, and medicaments related thereto are disclosed herein.
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Page/Page column 21
(2008/12/04)
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- Meldrum's acids as acylating agents in the catalytic intramolecular Friedel-Crafts reaction
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(Chemical Equation Presented) The intramolecular Friedel-Crafts acylation of aromatics with Meldrum's acid derivatives catalyzed by metal trifluoromethanesulfonates is reported. Meldrum's acids are easily prepared, functionalized, handled, and purified. The synthesis of polysubstituted 1-indanones from benzyl Meldrum's acids was investigated thoroughly, and it was shown that a variety of catalysts were effective, while accommodating a diversity of functional groups under mild conditions. The scope, limitations, and functional group tolerance (terminal alkene and alkyne, ketal, dialkyl ether, dialkyl thioether, aryl methyl ether, aryl TIPS and TBDPS ethers, nitrile- and nitro-substituted aryls, alkyl and aryl halides) for a variety of 5-benzyl (enolizable Meldrum's acids) and 5-benzyl-5-substituted Meldrum's acids (quaternized Meldrum's acids), forming 1-indanones and 2-substituted-1- indanones, respectively, are delineated. This method was further applied to the synthesis of 1-tetralones, 1-benzosuberones, and the potent acetylcholinesterase inhibitor donepezil. Rate of cyclization as a function of ring size was established for various benzocyclic ketones via competition experiments: 1-tetralones form faster than both 1-indanones and 1-benzosuberones, and 1-benzosuberones cyclize faster than 1-indanones.
- Fillion, Eric,Fishlock, Dan,Wilsily, Ashraf,Goll, Julie M.
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p. 1316 - 1327
(2007/10/03)
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- Convenient Access to Polysubstituted 1-Indanones by Sc(OTf) 3-Catalyzed Intramolecular Friedel-Crafts Acylation of Benzyl Meldrum's Acid Derivatives
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(Matrix presented) The intramolecular Friedel-Crafts acylation of benzyl Meldrum's acids is catalyzed by Sc(OTf)3 under mild reaction conditions. Several polysubstituted 1-indanones have been prepared.
- Fillion, Eric,Fishlock, Dan
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p. 4653 - 4656
(2007/10/03)
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- Indanylidenes. 1. Design and synthesis of (E)-2-(4,6-difluoro-1-indanylidene)acetamide, a potent, centrally acting muscle relaxant with antiinflammatory and analgesic activity
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The design of rigid cyclic analogues derived from cinnamamide 1, (E)-N-cyclopropyl-3-(3-fluorophenyl)prop-2-enamide, and β-methylcinnamamide 2, (E)-N-cyclopropyl-3-(3-fluorophenyl)but-2-enamide, has led to the discovery of the potent, centrally acting muscle relaxant (E)-2-(4,6-difluoro-1-indanylidene)acetamide, 17. Compound 17 also possesses potent antiinflammatory and analgesic activity. This paper describes the synthesis and the muscle relaxant, antiinflammatory, and analgesic structure-activity relationships of 17 and 67 of its analogues. Compound 17 has been taken into phase I clinical trials.
- Musso, David L.,Cochran, Felicia R.,Kelley, James L.,McLean, Ed W.,Selph, Jeffrey L.,Rigdon, Greg C.,Orr, G. Faye,Davis, Ronda G.,Cooper, Barrett R.,Styles, Virgil L.,Thompson, James B.,Hall, William R.
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p. 399 - 408
(2007/10/03)
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- Electron-transfer-induced tautomerization in methylindanones: Electronic control of the tunneling rate for enolization
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The radical cations generated from 4-methyl- and 4,7-dimethylindanone, as well as their deuterated isotopomers, isolated in Argon matrices, were found to undergo enolization to the corresponding enol radical cations at rates that differ by orders of magnitude. It is shown by quantum chemical calculations that the effect of the remote methyl group in the 4-position is of purely electronic nature in that it stabilizes the unreactive π-radical relative to the reactive σ-radical state of the 7-methylindanone radical cation. The observed kinetic behavior of the two compounds can be reproduced satisfactorily on the basis of calculated heigth and width of the thermal barrier for enolization, using the Bell model for quantum mechanical tunneling. High-level calculations on the methylacrolein radical cation show that barriers for enolization in radical cations are overestimated by B3LYP/6-31G*.
- Bednarek,Zhu,Bally,Filipiak,Marcinek,Gebicki
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p. 2377 - 2387
(2007/10/03)
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- An expeditious preparation of all enantiopure diastereoisomers of aromatic A-ring analogues of strigolactones, germination stimulants for seeds of the parasitic weeds Striga and Orobanche
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An expeditious manner to prepare all enantiopure diastereomers of aromatic A-ring strigolactone analogues is described. The racemic diastereoisomers of 8-methyl GR 24 and of its regioisomer 6-methyl GR 24 were prepared and separated, and subsequently chro
- Wigchert, Suzanne C. M.,Zwanenburg, Binne
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p. 2617 - 2623
(2007/10/03)
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- Integrated chemical process: One-pot aromatization of cyclic enones by the double elimination methodology
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A variety of aromatic hydrocarbons bearing multiple alkyl substituents are accessible with perfect regiocontrol in a one-pot reaction starting from cyclo-hexenones and their aromatic analogues [Eq. (1)]. The present methodology can be further extended to the synthesis of polycyclic aromatic hydrocarbons. The drawbacks encountered in the Friedel-Crafts reaction are resolved since the reaction proceeds under basic conditions.
- Orita, Akihiro,Yaruva, Jayamma,Otera, Junzo
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p. 2267 - 2270
(2007/10/03)
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- Synthesis and Na+/H+ exchange inhibitory activity of indanylideneacetylguanidines
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Synthesis of indanylideneacetylguadines 7a-i and their corresponding reduced compounds 8a-e has been achieved and their Na+/H+ exchange inhibitory activity evaluated. All the compounds studied exhibit significant inhibition of Na+/H+ exchanger activity. Promising activity is shown by compounds 7g, 8b and 8d. From the structure activity analysis, it appears that reduction of exocyclic double bond is associated with a marked increase in inhibitory activity.
- Ramakrishna,Jain,Ghate,Gupte,Vadlamudi
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p. 407 - 412
(2007/10/03)
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- An N.M.R. Investigation of the Mills-Nixon Effect
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The 4J coupling constant, previously established as a probe of bond order, was used to examine the bond orders in a series of ortho-bridged compounds: benzocyclopropene, 1,2-dihydrobenzocyclobutene, indan and tetralin.No evidence for sterically induced bond fixation (i.e. the Mills-Nixon effect) was found, but some evidence for electronic distortion in the corresponding benzylic ketones was observed.The experimental results are in accord with SCF/MO calculations.
- Collins, Michael J.,Gready, Jill E.,Sternhell, Sever,Tansey, Charles W.
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p. 1547 - 1557
(2007/10/02)
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- Steric Effects in the Synthesis of 1,7-Dialkylindans
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Synthesis routes to 1-alkyl(CH3,C2H5,i-C3H7)-6-methylindans and 1-alkyl(CH3,C2H5,i-C3H7)-7-methylindans are described.Members of the latter series, especially 1-isopropyl-7-methylindan, are sterically hindered through a peri interaction.This effect manifests itself throughout the study and necessitated use of alternative synthesis routes.Yields in the Grignard, Peterson olefination, Reformatsky, and Wittig reactions as well as catalytic hydrogenation and Li/NH3 reduction of α,β-unsaturated acids were compared.
- Budhram, Ronald S.,Palaniswamy, Ventakapuran A.,Eisenbraun, Edmund J.
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p. 1402 - 1406
(2007/10/02)
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- Some Reactions of 2-Ethenyl-4,4-ethylenedioxy-1-methylcyclohex-1-ene Prepared by Pyrolysis of 5,5-Ethylenedioxy-7a-methyl-4,5,6,7-tetrahydro-2H-inden-1(7aH)-one
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Flash vacuum pyrolysis of 5,5-ethylenedioxy-7a-methyl-4,5,6,7-tetrahydro-2H-inden-1(7aH)-one (2) at 630 deg gave a good yield of 2-ethenyl-4,4-ethylenedioxy-1-methylcyclohex-1-ene (6), but at 740 deg p-cresol was the major product.The diene acetal (6) was also obtained by pyrolysis of 5,5-ethylenedioxy-1β-hydroxy-7aβ-methyl-1,2,5,6,7,7a-hexahydro-4H-indene-1α-carbonitrile (3) at 600 deg.Pyrolytic reactions of 7a-methyl-2,3,7,7a-tetrahydro-1H-indene-1,5(6H)-dione (1), 5,5-ethylenedithio-7a-methyl-2,3,5,6,7,7a-hexahydro-1H-inden-1-one (7) and of 1,1-ethylenedioxy-3,5,5 -trimethylcyclohex-3-ene (8) are also described.Mild hydrolysis of the diene acetal (6) afforded 3-ethenyl-4-methylcyclohex-3-en-1-one (9) which upon brief treatment with dry hydrogen chloride in chloroform at 0 deg gave, after preparative thin-layer chromatography, a low yield of pure 3-ethenyl-4-methylcyclohex-2-en-1-one (11).The diene acetal (6) failed to undergo Diels-Alder reactions even at high pressures with Lewis acid catalysts, and it reacted anomalously with two molecules of 4-phenyl-1,2,4-triazoline-3,5-dione; the isomeric diene acetal 1-ethenyl-3,3-ethylenedioxy-6-methylcyclohex-1-ene (18) gave the expected Diels-Alder adduct with this reagent.
- Brown, Roger F.C.,Burge, Geoffrey L.,Collins, David J.
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p. 2295 - 2304
(2007/10/02)
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- Modern Friedel-Crafts chemistry XIII. Intra- and intermolecular cyclization of some carbonyl derivatives under Friedel-Crafts conditions
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Carbonyl group deactivation in the cycloalkylation of aryl haloalkyl ketones was studied.Ketones 1-5 were prepared and subjected to treatment with AlCl3, AlCl3/H2SO4 and H2SO4 catalysts.Whereas AlCl3 catalyst gave no cyclization products, the use of AlCl3/H2SO4 and H2SO4 catalysts afforded the corresponding indanones and/or tetralones (6-11).The intermediate p-methylacrylophenone (12) was also obtained in the case of ketone 2.Furthermore intermolecular cyclizations of benzene, toluene and p-xylene with 3-chloropropionyl chloride (13) and 4-chlorobutyryl chloride (14) were investigated.In the presence of AlCl3/CH3NO2 catalyst, only the corresponding aryl haloalkyl ketones (1-5) were formed whereas the use of AlCl3 catalyst gave, in addition, some cyclic ketones.However, the use of AlCl3/H2SO4 catalyst gave only the corresponding cyclic ketones (6-11).Results are discussed and mechanisms are suggested.In conclusion, carbonyl group deactivation for ring closure is demonstrated in the investigated ketones and cyclization can only effected under strenuous conditions.
- Khalaf, Ali A.,Abdel-Wahab, Aboel-Magd A.,El-Khawaga, Ahmed M.,El-Zohry, Maher F.
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p. 285 - 291
(2007/10/02)
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- Stereopopulation Control. 8. Rate and Equilibrium Enhancement in the Formation of Homophthalic Anhydrides
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The kinetics of cyclization of α,α,3,4,6-pentamethylhomophthalic acid have been measured in sovent acetonitrile at 28.5 deg C, using as catalysts a series of acids ranging in strength from perchloric to acetic.In the presence of 0.12 M HClO4, t1/2 for acid anhydride formation = 0.3 s.For the stronger acid catalysts, kcycl is a linear function of catalyst concentration; for the weak acids, however, a change in rate-limiting step is revealed by curvature in the plots of ktotobsd vs. .All the weak acids show the same limiting value, 6.45E-3 min-1; this value is considered to be the rate constant for uncatalyzed formation of the tetrahedral intermediate.Homoconjugate bases (HA2(-)) of the weak acids show a similar curvature in their dilution plots, and the same limiting rate constant as for weak acids.Two independent and competitive pathways for cyclization are proposed.For strong acid catalysis, an intermediate acylium ion is considered on the basis of Broensted α = -0.79, kH/kD ca. 1, and acceleration of anhydride hydrolysis by methyl substituents.A value of ΔSexcit. = -23 eu suggests that cyclization, rather than acylium ion formation, is rate limiting.For weak acid catalysis, α = -0.17, kH/kD = 4.3, ΔSexcit. = -31 eu, and methyl groups retard anhydride hydrolysis by electron release; for this pathway, catalyzed breakdown of a tetrahedral intermediate is considered rate limiting.The composite Broensted plot is curved because the two pathways follow different rate laws.In contrast to rate enhancement results for phenolic lactone formation, the pentamethylhomophthalic acid is only sevenfold as reactive as α,α-dimethylhomophthalic acid.For the catalyst acids, pK(acetonitrile) is shown to be a linear function of pK(H2O) over the entire range of acids examined.
- Hillery, Paul S.,Cohen, Louis A.
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p. 2760 - 2770
(2007/10/02)
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- Carbon-13 Nuclear Magnetic Resonance Spectra of Pterosin-Sesquiterpenes and Related Indan-1-one Derivatives
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Methyl derivatives of indan-1-one were prepared as models to aid in interpreting the carbon-13 nuclear magnetic resonance ((13)C-NMR) spectra of pterosin-sesquiterpenes which were isolated from bracken fern, Pteridium aquilinum var. latiusculum.The chemical shifts of the carbons of the methylindan-1-ones were assigned by the proton decoupling technique.All the (13)C-NMR signals of the pterosin-sesquiterpenes were assigned by means of selective proton decouplings, and from the (13)C-(1)H long-range couplings and (13)C chemical shifts of the model compounds.Keywords - indan-1-one derivative; methylindan-1-one; pterosin-sesquiterpene; methylindan-1-one synthesis; (1)H-NMR; (13)C-NMR; selective decoupling; C-H decoupling
- Fukuoka, Masamichi,Yoshihira, Kunitoshi,Natori, Shinsaku,Mihashi, Kunihide,Nishi, Masatoshi
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p. 3113 - 3128
(2007/10/02)
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