3900-45-6Relevant articles and documents
Remarkable effect of lithium salts in Friedel-Crafts acylation of 2-methoxynaphthalene catalyzed by metal triflates
Kobayashi,Komoto
, p. 6463 - 6465 (2000)
In the presence of a catalytic amount of a metal triflate such as Sb(OTf)3 or Ga(OTf)3, 2-methoxynaphthalene reacted with acetic anhydride in nitromethane-lithium perchlorate to afford 2-acetyl-6-methoxynaphthalene, a well-known intermediate for the synthesis of naproxen, in a high yield. (C) 2000 Elsevier Science Ltd.
Synthesis of bridged biarylbisquinones and effects of biaryl dihedral angles on photo- and electro-chemical properties
Wongma, Krittaphat,Bunbamrung, Nantiya,Thongpanchang, Tienthong
, p. 1533 - 1540 (2016)
A series of bridged biarylbisquinones, QBINOLs 1-4, and their corresponding monomers, QNaphs 5-6, were designed to demonstrate the influence of biaryl conformation on the photo- and electro-chemical properties of the molecules. All target compounds were synthesized from the Diels-Alder reaction between silyl enol ethers of the corresponding naphthyl or binaphthyl derivatives and p-benzoquinone. Addition of an OMe auxochrome or formation of the dimeric structures affect the absorption spectra and the energy band gap (Eg), but not the reduction potentials of the molecules. Narrowing the dihedral angles of the QBINOLs by shortening methylene bridges limited the contribution of bridging OR auxochromes and therefore resulted in lower HOMO levels and larger Eg.
Fluorogenic kinetic assay for high-throughput discovery of stereoselective ketoreductases relevant to pharmaceutical synthesis
Thai, Yen-Chi,Szekrenyi, Anna,Qi, Yuyin,Black, Gary W.,Charnock, Simon J.,Fessner, Wolf-Dieter
, p. 1320 - 1326 (2018)
Enantiomerically pure 1-(6-methoxynaphth-2-yl) and 1-(6-(dimethylamino)naphth-2-yl) carbinols are fluorogenic substrates for aldo/keto reductase (KRED) enzymes, which allow the highly sensitive and reliable determination of activity and kinetic constants of known and unknown enzymes, as well as an immediate enantioselectivity typing. Because of its simplicity in microtiter plate format, the assay qualifies for the discovery of novel KREDs of yet unknown specificity among this vast enzyme superfamily. The suitability of this approach for enzyme typing is illustrated by an exemplary screening of a large collection of short-chain dehydrogenase/reductase (SDR) enzymes arrayed from a metagenomic approach. We believe that this assay format should match well the pharmaceutical industry's demand for acetophenone-type substrates and the continuing interest in new enzymes with broad substrate promiscuity for the synthesis of chiral, non-racemic carbinols.
Acylation of 2-methoxynaphthalene and isobutylbenzene over zeolite beta
Andy,Garcia-Martinez,Lee,Gonzalez,Jones,Davis
, p. 215 - 223 (2000)
The acylation of 2-methoxynaphthalene (2MN) and isobutylbenzene using several zeolite beta samples having varius Si/Al ratios and crystal sizes to examine whether external surface sites could be eliminated to enhance the catalyst performance to obtain a viable acylation catalyst for the formation of precursors to the nonsteroidal anti-inflammatory agents naproxen and ibuprofen. Zeolite beta was active for the acylation of 2MN but was not selective to the desired product, 2-acetyl-6-methoxynaphthalene (2,6-AMN). Mild operating conditions (temperature and acylating agent concentration) could be used to obtain reasonable conversions and to limit catalyst deactivation. The other key product, 1-acetyl-2-methoxynaphthalene (1,2-AMN) formed on the external surface of the zeolite, while 2,6-AMN occurred in the zeolite pores. Thus, the selectivity to 2,6-AMN was enhanced on zeolite beta samples having a larger crystal size, on which most of the acid sites could be passivated by coating the crystals with a layer of amorphous silica. The amount of surface coating on the large crystals determined the yield of and the selectivity to 2,6-AMN. Isobutylbenzene was less reactive than 2MN but the desired product, 4-isobutylacetophenone, was always obtained since the isobutyl group provides for the para position being the preferred sites for acylation. For isobutylbenzene, the zeolite external surface contributed significanlty to the formation of 4-isobutylacetophenone. Zeolite beta with a small crystal size was, thus, the most favored catalyst for this reaction.
Oxidation of 2-methoxy-6-(1-methylethyl)naphthalene with oxygen
Orlinska, Beata,Stec, Zbigniew,Zawadiak, Jan
, p. 295 - 301 (2012)
Aerobic oxidation of 2-methoxy-6-(1-methyl-ethyl)naphthalene to hydroperoxide, alcohol, and ketone, is reported. These compounds, particularly 2-acetyl-6-meth-oxynaphthalene, are important intermediates in naproxen synthesis. N-Hydroxyphthalimide is shown here to be an efficient catalyst for oxidation to the hydroperoxide, 2-methoxy-6-(1-hydroperoxy-1-methylethyl) naphthalene, with a yield of 87%. However, the ketone and alcohol were obtained with lower yields, with a maximum yield of 13% for the ketone and 27% for the alcohol, using N-hydroxyphthal-imide and Cu(II) acetylacetonate as a catalyst. The synthesis of the products 2-acetyl-6-methoxynaphthalene and 2-methoxy-6-(1-hydroxy-1-methylethyl)naphthalene via an initial oxidation step to the hydroperoxide followed by a hydroperoxide decomposition step is shown to be more efficient; the ketone and alcohol were obtained from 2-methoxy-6-(1-methylethyl)naphthalene with yields of 40 and 56%, respectively.
Zeolite catalyzed highly selective synthesis of 2-methoxy-6-acetylnaphthalene by Friedel-Crafts acylation of 2-methoxynaphthalene in acetic acid reaction media
Yamazaki, Tomoyoshi,Makihara, Makoto,Komura, Kenichi
, p. 170 - 176 (2017)
Zeolite catalyzed Friedel-Crafts acetylation of 2-methoxynaphthalene to produce 2-methoxy-6-acetylnaphthalene with high selectivity and conversion has been a challenging task, because the obtained compound is a key intermediate for an anti-inflammatory agent, Naproxen. However, no satisfactory results have been obtained with zeolite catalysts, and harmful solvents have been used to gain a high selectivity together with a high conversion. Here, we report the synthesis of 2-methoxy-6-acetylnaphthalene from 2-methoxynaphthalene with a high selectivity and a high conversion under an unprecedented simple reaction system; acetic anhydride as an acetylating agent, acetic acid as a solvent, and proton-type zeolite catalysts with low acidity. Among the examined zeolites, a proton-type H-MOR (SiO2/Al2O3 = 200) with a low acid content shows a conversion of 82% and an 86% selectivity for 2-methoxy-6-acetylnaphthalene. Further, detailed control experiments using H-MOR catalyst in acetic acid solvent were carried out to propose a plausible reaction mechanism.
Direct Enantio- and Diastereoselective Oxidative Homocoupling of Aldehydes
N?sborg, Line,Leth, Lars A.,Reyes-Rodríguez, Gabriel J.,Palazzo, Teresa A.,Corti, Vasco,J?rgensen, Karl Anker
, p. 14844 - 14848 (2018)
A novel strategy for the direct enantioselective oxidative homocoupling of α-branched aldehydes is presented. The methodology employs open-shell intermediates for the construction of chiral 1,4-dialdehydes by forming a carbon–carbon bond connecting two quaternary stereogenic centers in good yields and excellent stereoselectivities for electron-rich aromatic aldehydes. The 1,4-dialdehydes were transformed into synthetically valuable chiral pyrrolidines. Experimental mechanistic investigations based on competition experiments combined with computational studies indicate that the reaction proceeds through a radical cation intermediate and that reactivity and stereoselectivity follow different trends.
Naproxen sodium salt photochemistry in aqueous sodium dodecyl sulfate (SDS) ellipsoidal micelles
Valero,Sultimova, Natalya B.,Houston, Judith E.,Levin, Peter P.
, (2020/11/27)
The photochemistry and other properties of the anti-inflammatory drug (NSAID) naproxen (NP) in sodium dodecyl sulfate, SDS, micellar aqueous solutions at pH = 7 (NP is in anionic form) were studied. The large value of the partition coefficient (P) was obtained, logP = 2.7, showing that the most part of NP is localized in the micellar phase. The solubilization in SDS micelles results in NP fluorescence and photodegradation quantum yields decrease. The photoproducts 6-methoxy-2-(1-hydroxyethyl)-naphthalene and 6-methoxy-2-acetyl-naphthalene were found by gas chromatography/mass spectrometry (GC/MS). Both photoproducts were formed in SDS solution in significantly smaller amounts than in water. Small angle neutron scattering (SANS) showed that the presence of NP has small effect on the micellar structure. Only a slight decrease of the ionization degree of the micelle was observed by SANS, suggesting that NP was localized in the vicinity of micellar surface. The NP triplet excited state, hydrated electron, NP radical cation and some other relatively long lived intermediate were observed by laser flash photolysis of NP in micellar solution. The decay kinetics of these intermediates was different with respect to that in the homogeneous media. The reactivity of NP in SDS micellar environment was compared to that in the homogeneous media and the probable nature of the intermediate precursors of the final photoproducts are under the discussion.
Visible-light-promoted oxidative decarboxylation of arylacetic acids in air: Metal-free synthesis of aldehydes and ketones at room temperature
He, Shuaiqi,Chen, Xiaolan,Zeng, Fanlin,Lu, Peipei,Peng, Yuyu,Qu, Lingbo,Yu, Bing
supporting information, p. 1863 - 1867 (2020/01/03)
A metal-free photocatalytic oxidative decarboxylation reaction at room temperature was developed for the synthesis of aromatic aldehydes and ketones from the corresponding arylacetic acids. The reaction was realized under blue-light irradiation by adding 1 molpercent of 4CzIPN as photocatalyst and air as oxidant. This reaction represents a novel decarboxylation of a sp3-hybridized carboxylic acids without traditional heating, additional oxidants, and metal reagents under mild conditions.
