- Formation of Phenalenone Skeleton by an Unusual Rearrangement Reaction
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The frame rearrangement reaction of dinaphthyl ketones, possessing hydroxy groups at appropriate positions, into phenalenone derivatives under acidic conditions was discovered serendipitously. Although this rearrangement had limited scope, its mechanism was unusual, involving the division of naphthalene rings into one phenalenone ring and one benzene ring. The reaction mechanism was elucidated by direct determination of intermediate structures using 1H NMR measurements. The generated phenalenones are expected to be key intermediates toward natural products and functional materials.
- Sasaki, Sayaka,Azuma, Eriko,Sasamori, Takahiro,Tokitoh, Norihiro,Kuramochi, Kouji,Tsubaki, Kazunori
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- Effects of alkali and alkaline earth metals on the Kolbe-Schmitt reaction
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It was found that the carboxylations of magnesium, calcium, and barium phenoxides with carbon dioxide at 260 °C produced salicylic acid and dicarboxylic acids (4-hydroxyisophthalic acid and 2-hydroxyisophthalic acid) in very high yields (80-100%), exceeding that of the ordinary Kolbe-Schmitt reaction. The orientation (ortho/para ratio) was controlled not only by chelations of the intermediate with alkaline earth metal (Mg, Ca, Ba) ions, resulting in salicylic acid, but also by the sizes of metal ions (Rb, Cs), giving p-hydroxybenzoic acid in a much higher ratio than the widely used method with potassium or sodium phenoxide. These alkaline earth metals worked to produce 3-hydroxy-2-naphthoic acid by the reaction of 2-naphthoxide with carbon dioxide, but the yield of 6-hydroxy-2-naphthoic acid was comparable to that of 3-hydroxy-2-naphthoic acid when cesium or rubidium 2 naphthoxide was employed. Considerably high yields (～60%) of 6-hydroxy-2-naphthoic acid, a monomer of one of the best liquid-crystal polymers, was attained by the carboxylation of cesium or rubidium 2-naphthoxide in the presence of potassium or sodium carbonate, where the alkali metal ion was supposed to increase the reactivity of the substrate. The formation of "binol" was observed in the preparation of 2-naphthoxides with metal hydroxides, especially with copper(II) ion.
- Rahim, Mohammad Abdur,Matsui, Yoshihisa,Kosugi, Yoshio
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- Preparation method of 6-hydroxy-2-naphthoic acid
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The invention provides a preparation method of 6-hydroxy-2-naphthoic acid, and particularly relates to the field of chemical processes. Herein, the ethyl 6-isopropyl-2-naphthoate is used as a raw material, isopropyl is hydroxylated through free radical reaction to prepare ethyl 6-hydroxy-2-naphthoate, and finally, the target product 6-hydroxy-2-naphthoic acid is prepared through hydrolysis and acidification. The method is mild in preparation condition, simple in equipment requirement and high in yield.
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Paragraph 0030; 0033-0035; 0039-0040; 0045; 0048-0049
(2021/11/27)
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- Synthesis and cytotoxicity of n-substituted dibenzo[a,j]xanthene-3,11-dicarboxamide derivatives
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In order to study the structure-activity relationships of xanthene derivatives, four series of N-substituted 14-aryl-14H-dibenzo[a,j]xanthene-3,11-dicarboxamide derivatives were synthesized. The structures of all compounds were identified by 1H-NMR HR-MS and IR spectra in which compounds 6a-h were further identified by 13C-NMR spectra. The in vitro antitumor activity of the synthesized compounds was tested by MTT assay. Most of them displayed strong inhibitory activity on human hepatocellular carcinoma cell lines (SK-HEP-1 HepG2 and SMMC-7721 cells) and acute promyelocytic leukemia NB4 cells. Compounds 6c-6e exhibited significant inhibitory activity against NB4 cells with IC50 values of 0.52 μM and 0.76 μM respectively much lower than 5.31 μM of the positive control As2O3.
- Song, Yongbin,Yang, Yihui,Wu, Lijun,Dong, Naiwei,Gao, Shang,Ji, Hongrui,Du, Xia,Liu, Bo,Chen, Guoyou,Dembinski, Roman
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- Production of aromatic hydroxycarboxylic acid
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PROBLEM TO BE SOLVED: To provide an environment-friendly method for producing aromatic hydroxycarboxylic acid in high yield even under low temperature reaction conditions. SOLUTION: The method for producing aromatic hydroxycarboxylic acid includes a process of reacting an alkali metal salt of an aromatic hydroxy compound with carbon dioxide in a medium, where the reaction is performed in the presence of 0.01-1.0 mole of one or more alcohol compounds and/or ether compounds for 1 mole of the alkali metal salt of the aromatic hydroxy compound. COPYRIGHT: (C)2013,JPOandINPIT
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Paragraph 0047
(2018/07/14)
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- Production of aromatic hydroxycarboxylic acid
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PROBLEM TO BE SOLVED: To provide a production method capable of obtaining aromatic hydroxycarboxylic acid at high yield even under a reaction condition at low temperature. SOLUTION: The method for production of aromatic hydroxycarboxylic acid includes a process of reacting an alkali metal salt of aromatic hydroxy compounds with carbon dioxide in a medium. The method is characterized by performing the above reaction in the presence of a ligand alone or as its metal complex of 0.01-1.0 mol based on 1 mol of the alkali metal salt of the aromatic hydroxy compound. COPYRIGHT: (C)2012,JPOandINPIT
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Paragraph 0065-0067; 0069-0070; 0071-0072
(2018/05/17)
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- N-heterocyclic carbene-assisted, Bis(phosphine)nickel-catalyzed cross-couplings of diarylborinic acids with aryl chlorides, tosylates, and sulfamates
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Efficient bis(phosphine)nickel-catalyzed cross-couplings of diarylborinic acids with aryl chlorides, tosylates, and sulfamates have been effected with an assistance of N-heterocyclic carbene (NHC) generated in situ from N,N′-dialkylimidazoliums, e.g., N-butyl-N′-methylimidazolium bromide ([Bmim]Br), in toluene using K3PO4·3H2O as base. In contrast to bis(NHC)nickel-catalyzed conventional Suzuki coupling of arylboronic acids, mono(NHC)bis(phosphine)nickel species generated in situ from Ni(PPh3)2Cl2/[Bmim]Br displayed high catalytic activities in the cross-couplings of diarylborinic acids. The structural influences from diarylborinic acids were found to be rather small, while electronic factors from aryl chlorides, tosylates, and sulfamates affected the couplings remarkably. The couplings of electronically activated aryl chlorides, tosylates, and sulfamates could be efficiently effected with 1.5 mol % NiCl2(PPh3)2/[Bmim]Br as catalyst precursor to give the biaryl products in excellent yields, while 3-5 mol % loadings had to be used for the couplings of non- and deactivated ones. A small ortho-substitutent on the aromatic ring of aryl chlorides, tosylates, and sulfamates was tolerable. Applicability of the nickel-catalyzed cross-couplings in practical synthesis of fine chemicals has been demonstrated in process development for a third-generation topical retinoid, Adapalene.
- Ke, Haihua,Chen, Xiaofeng,Zou, Gang
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p. 7132 - 7140
(2014/08/18)
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- Design, synthesis and anticancer activity of N3,N 11-bis(2-hydroxyethyl)-14-aryl-14H-dibenzo[a,j]xanthenes-3, 11-dicarboxamide
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A series of novel N3,N11-bis(2-hydroxyethyl)-14-aryl- 14H-dibenzo[a,j]xanthenes-3,11-dicarboxamide, three N3,N 11-bis(2-hydroxyethyl)-14-aryl-14H-dibenzo[a,j]xanthene-3, 11-dimethanamine derivatives and their intermediates 14-aryl-14H-dibenzo[a,j] xanthenes-3,11-dicarboxylic acid, were synthesized, and the structures of which were characterized by 1H-NMR, 13C-NMR, high resolution (HR)-MS, and IR spectra. The antitumor activities of these molecules were evaluated on five cancer cell lines. The results of in vitro assay against human hepatocellular carcinoma cell lines (SK-HEP-1 and HepG2 and SMMC-7721 cells), acute promyelocytic leukemia NB4 cells and uterine cervix cancer HeLa cells, show several compounds to be endowed with cytotoxicity in micromolar to submicromolar range. The carboxamide derivatives 6c and 6e exhibitted good inhibition on NB4 cancer cells, and the IC50 values of which were 0.82 μm and 0.96 μm, respectively, much lower than 5.01 μm of the positive control As2O3. Flow cytometric analysis results revealed that compounds 6e and 6f may induce tumor cell apoptosis.
- Song, Yongbin,Yang, Yihui,You, Jun,Liu, Bo,Wu, Lijun,Hou, Yunlong,Wang, Wenji,Zhu, Jiuxin
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p. 167 - 175
(2013/03/28)
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- Investigation of the substrate range of CYP199A4: Modification of the partition between hydroxylation and desaturation activities by substrate and protein engineering
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The cytochrome P450 enzyme CYP199A4, from Rhodopseudomonas palustris HaA2, can efficiently demethylate 4-methoxybenzoic acid. It is also capable of oxidising a range of other related substrates. By investigating substrates with different substituents and ring systems we have been able to show that the carboxylate group and the nature of the ring system and the substituent are all important for optimal substrate binding and activity. The structures of the veratric acid, 2-naphthoic acid and indole-6-carboxylic acid substrate-bound CYP199A4 complexes reveal the substrate binding modes and the side-chain conformational changes of the active site residues to accommodate these larger substrates. They also provide a rationale for the selectivity of product oxidation. The oxidation of alkyl substituted benzoic acids by CYP199A4 is more complex, with desaturation reactions competing with hydroxylation activity. The structure of 4-ethylbenzoic acid-bound CYP199A4 revealed that the substrate is held in a similar position to 4-methoxybenzoic acid, and that the C β C-H bonds of the ethyl group are closer to the heme iron than those of the Cα (3.5 vs. 4.8 A?). This observation, when coupled to the relative energies of the reaction intermediates, indicates that the positioning of the alkyl group relative to the heme iron may be critical in determining the amount of desaturation that is observed. By mutating a single residue in the active site of CYP199A4 (Phe185) we were able to convert the enzyme into a 4-ethylbenzoic acid desaturase. Engineering a P450 desaturase: The substrate range of CYP199A4 from Rhodopseudomonas palustris was investigated. The partition between the hydroxylation and desaturation activities of 4-ethylbenzoic acid was studied by changing the substrate and by mutation. The activity of CYP199A4 with 4-ethylbenzoic acid was changed to a desaturase by a single mutation at F185. Copyright
- Bell, Stephen G.,Zhou, Ruimin,Yang, Wen,Tan, Adrian B. H.,Gentleman, Alexander S.,Wong, Luet-Lok,Zhou, Weihong
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p. 16677 - 16688
(2013/03/28)
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- Synthesis of 6-hydroxy-2-naphthoic acid from 2,6-diisopropylnaphthalene using NHPI as a key catalyst
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A new strategy to 6-hydroxy-2-naphthoic acid (HNPA) and 4-hydroxybenzoic acid from 2,6-diisopropylnaphthalene and p-cymene, respectively, was developed using the NHPI-catalyzed aerobic oxidation as a principal reaction. 2,6-Diisopropylnaphthalene was oxidized by the oxidation with O2 (1 atm) by NHPI (10 mol %) combined with Co(OAc)2 (0.5 mol %) to give 6-acetyl-2-isopropylnaphthalene, which then was converted to 6-isopropyl-2-naphthoic acid under O2 (1 atm) in the presence of Co(OAc)2 (0.5 mol %) and Mn(OAc)2 (0.5 mol %). Esterification of the resulting acid followed by the aerobic oxidation produced methyl 6-hydroxy-2-naphthoate whose hydrolysis led to the desired HNPA. An alternative route involves the oxidation of 6-acetyl-2-isopropylnaphthalene to 6-acetyl-2-naphthol on which subsequent oxidation and deacetylation gave HNPA. This method was successfully extended to the synthesis of 4-hydroxybenzoic acid from p-cymene.
- Nakamura, Ryota,Obora, Yasushi,Ishii, Yasutaka
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experimental part
p. 3577 - 3581
(2009/09/06)
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- Process for dehydrating hydrous sodium Beta-naphtholate
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The present invention provides a process for dehydrating hydrous sodium β-naphtholate comprising: the step of heating the hydrous sodium β-naphtholate or a mixture of the hydrous sodium β-naphtholate and β-naphthol which comprises no more than 0.2 mole of β-naphthol per one mole of sodium β-naphtholate in a solvent at a temperature of 260-300°C under an inert gas. The process makes it possible to dehydrate hydrous sodium β-naphtholate thoroughly in a short time with less production of tarry components.
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Page/Page column 7
(2010/02/10)
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- Utilization of a peptide lead for the discovery of a novel PTP1B-binding motif
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Examination of the PTP1B inhibitory potency of an extensive series of phosphotyrosyl (pTyr) mimetics (Xxx) expressed in the EGFr-derived hexapeptide platform Ac-Asp-Ala-Asp-Xxx-Leu-amide previously led to the finding of high inhibitory potency when Xxx = 4-(phosphonodifluoromethyl)phenylalanyl (F2Pmp) (Ki = 0.2 μM) and when Xxx = 3-carboxy-4-carboxy-methyloxyphenylalanyl (Ki = 3.6 μM). In the first instance, further work led from the F2Pmp-containing peptide to monomeric inhibitor, 6-(phosphonodifluoromethyl)-2-naphthoic acid (Ki = 22 μM), and to the pseudo-dipeptide mimetic, N-[6-(phosphonodifluoromethyl)-2-naphthoyl]-glutamic acid (Ki = 12 μM). In the current study, a similar approach was applied to the 3-carboxy-4-carboxymethyloxyphenylalanyl-containing peptide, which led to the preparation of monomeric 5-carboxy-6-carboxymethyloxy-2-naphthoic acid (Ki = 900 μM). However, contrary to expectations based on the aforementioned F2Pmp work, incorporation of this putative pTyr mimetic into the pseudo-dipeptide, N-[5-carboxy-6-carboxymethyloxy-2-naphthoyl]-glutamic acid, resulted in a substantial loss of binding affinity. A reevaluation of binding orientation for 5-carboxy-6-carboxymethyloxy-2-naphthoic acid was therefore undertaken, which indicated a 180° reversal of the binding orientation within the PTP1B catalytic site. In the new orientation, the naphthyl 2-carboxyl group, and not the o-carboxy carboxymethyloxy groups, mimics a phosphoryl group. Indeed, when 5-carboxy-2-naphthoic acid itself was examined at neutral pH for inhibitory potency, it was found to have Ki = 31 ± 7 μM, which is lower than parent 5-carboxy-6-carboxymethyloxy-2-naphthoic acid. In this fashion, 5-carboxy-2-naphthoic acid (or more appropriately, 6-carboxy-1-naphthoic acid) has been identified as a novel PTP1B binding motif.
- Gao,Voigt,Zhao,Pais,Zhang,Wu,Zhang,Burke Jr.
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p. 2869 - 2878
(2007/10/03)
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- COLUMNAR CRYSTALS OF 6-HYDROXY-2-NAPHTHOIC ACID AND PROCESS FOR THE PRODUCTION THEREOF
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A process for manufacturing columnar crystals of 6-hydroxy-2-naphthoic acid comprising the steps of, dissolving crude 6-hydroxy-2-naphthoic acid product in an aqueous solvent, adding crystalline 3-hydroxy-2,7-naphthoic acid or columnar crystals as seed crystals, and cooling the mixture to precipitate the desired crystals. The present invention further provides columnar crystals of 6-hydroxy-2-naphthoic acid which have X-ray diffraction peaks 2θ in 16.8-17.8 and/or 21.3-22.3.
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- Mild deprotection of 2-(trimethylsilyl)ethyl esters
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A method for the deprotection of 2-(trimethylsilyl)ethyl (TMSE) esters is described. Treatment of carboxylic esters with NaH in DMF cleanly produces the deprotected acid after extractive work-up. This method can be applied to sterically-hindered substrates as well as esters containing fluoride-labile functionality. A tandem alkylation/ester deprotection procedure is also presented.
- Serrano-Wu, Michael H,Regueiro-Ren, Alicia,St. Laurent, Denis R,Carroll, Tina M,Balasubramanian, Balu N
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p. 8593 - 8595
(2007/10/03)
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- Process for preparing aromatic hydroxycarboxylic acids
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A process for preparing aromatic hydroxycarboxylic acids or di-salts thereof by reaction of alkali metal phenolates or naphtholates with carbon dioxide, in the presence or absence of a further alkali metal salt, which comprises introducing the solid phenolate or naphtholate starting materials and, if desired, the alkali metal salt into the reaction mixture batchwise or continuously, separately or together, in the form of a dispersion in an inert organic liquid. The process of the invention makes possible the preparation of aromatic hydroxycarboxylic acids in good yields and with high chemical selectivity. Additional measures for increasing the selectivity, as are described for the Kolbe-Schmitt reaction in, for example, EP-A 0 053 824, EP-A 0 081 753 and EP-A 0 254 596, can be omitted.
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- Process for releasing acidic organic compounds from salts thereof by carbon dioxide
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This invention embodies a process for releasing acidic organic compounds in high yield and good purity from aqueous solutions of their salts which comprises converting the salts by carbon dioxide to their corresponding free acidic organic compounds and metal hydrogen carbonates, removing the acidic organic compounds from the mixture by extraction with an essentially water-insoluble organic solvent, and re-extracting the organic phase with carbon dioxide containing water. Using this process, the acidic organic compounds are completely released from their corresponding salts, i.e., the organic solution is free of salt. The acidic organic compounds released by the claimed process are organic compounds which contain acidic protons which can be replaced by metals. Some examples are carboxylic acids, sulfonic acids, phosphonic acids, phenols, naphthols, and aliphatic alcohols.
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- Process for the preparation of 2-hydroxy-naphthalene-6-carboxylic acid
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2-Hydroxy-naphthalene-6-carboxylic acid or its dipotassium salt is obtained in a good yield and purity without substantial formation of the isomeric compound 2-naphthol-3-carboxylic acid by reacting potassium β-naphtholate with potassium carbonate in the presence of carbon monoxide at a temperature above 260° C. in potassium formate as the solvent.
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- Dioxane adducts of aromatic meta- or para-hydroxy-carboxlic acids
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The invention relates to the dioxane adducts of armoatic meta-or para-hydroxycarboxylic acids, which consist, per mole, of 1 mole of 1,4-dioxane and about 2 moles of hydroxycarboxylic acid. The invention further relates to a process for the preparation of these adducts, which comprises dissolving the hydroxycarboxylic acids in dioxane or a mixture of the latter with water or with an organic solvent and then allowing the adducts to crystallize.
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- Method for the manufacture of hydroxy aromatic monocarboxylic acids
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A method for preparing hydroxy aromatic carboxylic acids, or the ester derivatives thereof, comprises the carbonylation of a hydroxy aromatic bromide in the presence of a catalytic amount of a transition element of group VIII of the Periodic Table on a carbon support, at a pH of above 8, in the absence of any promoter.The reaction is carried out at a temperature in the range of between 140oC to 200oC. The resulting products are obtained in high yields and of high purity. The method has particular applicability to the manufacture of 6-carboxy-2-naphthol and 4-hydroxy-4'-carboxy-biphenyl.
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- Method of inhibiting leukotriene biosynthesis by oral administration of p-aminophenols or derivatives thereof
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A method is provided for inhibiting leukotriene biosynthesis and thus treating asthma, psoriasis or inflammation by oral administration of p-aminophenols having the structure STR1 wherein m is 0 to 5; X is CH or N; R1 and R2 may be the same or different and are H, lower alkyl, aryl, hydroxy, hydroxyalkyleneoxy, alkylthio, alkoxy, alkanoyloxy, aryloxy, halo, carboxy, alkoxycarbonyl or amido; R3 is H, lower alkyl, alkanoyl or aroyl; and R4 is H, lower alkyl, benzoyl or alkanoyl, and including acid-addition salts thereof, with the proviso that when R4 is benzoyl, R2 is other than H.
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- Process for producing azo pigment
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A process for producing an azo pigment, which comprises coupling an aromatic diazonium compound with 3-hydroxy-2-naphthoic acid and at least one binaphthol and optionally, laking the resulting pigment.
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- Quinoline compounds and compositions thereof
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p-Aminophenols are provided having the structure STR1 wherein m is 0 to 5; X is CH or N; R1 and R2 may be the same or different and are H, lower alkyl, aryl, hydroxy, hydroxyalkyleneoxy, alkylthio, alkoxy, alkanoyloxy, aryloxy, halo, carboxy, alkoxycarbonyl or amido; R3 is H, lower alkyl, alkanoyl or aroyl; and R4 is H, lower alkyl or alkanoyl, and including acid-addition salts thereof, with the proviso that when X is CH, m is 0 and R1 is H, and when R4 is H, R2 is other than alkoxy, H or hydroxy, and when R4 is benzoyl, R2 is other than H. These compounds together with the compounds defined in the above proviso are useful as inhibitors of leukotriene production and as such are useful as antiallergy, anti-inflammatory and anti-psoriatic agents.
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- Process for preparing 6-acetoxy-2-naphthoic-acid and pure 6-hydroxy-2-naphthoic acid
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6-Hydroxy-2-naphthoic acid can be selectively acetylated to 6-acetoxy-2-naphthoic acid, in particular in the presence of admixtures of isomeric hydroxy-naphthoic acids, and thus be separated from those isomeric admixtures. The acetylation is affected in aqueous alkaline solution by reaction with acetic anhydride. By hydrolysis of the 6-acetoxy-2-naphthoic acid, a pure 6-hydroxy-2-naphthoic acid is obtained.
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- COBALT-CATALYSED CARBONYLATION OF ARYL HALIDES
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A novel method for carbonylation of aromatic and heteroatomatic halides is described.The catalytic system consists of a combination of alkylcobalt carbonyl complexes, either performed or made "in situ", and bases such as alkoxides, NaOH and K2CO3 in aliphatic alcohols.Under these conditions new anionic cobalt complexes are formed which are characterized by a very high reactivity towards aromatic halides.The latter undergo the carbonylation reaction with high yield under very mild conditions.
- Foa, M.,Francalanci, F.,Bencini, E.,Gardano, A.
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p. 293 - 304
(2007/10/02)
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- Recycling techniques in the production of 6-hydroxy-2-naphthoic acid
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The production of 6-hydroxy-2-naphthoic acid from anhydrous potassium 2-naphthoxide and carbon dioxide is improved by introducing 3-hydroxy-2-naphthoic acid to the initial stages of the process.
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- Process for the production of 6-hydroxy-2-naphthoic acid
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The production of 6-hydroxy-2-naphthoic acid from anhydrous potassium 2-naphthoxide and carbon dioxide is improved by forming a mixture of 0.8-1.45 moles of 2-hydroxynaphthalene per equivalent of potassium base, dehydrating the mixture, adding carbon dioxide at about 20 to 90 psi at about 255°-280° C. and agitating and heating at said pressure and temperature.
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- Process for the production of 6-hydroxy-2-naphthoic acid
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The production of 6-hydroxy-2-naphthoic acid from anhydrous potassium 2-naphthoxide and carbon dioxide is improved by forming a mixture of 0.8-1.2 moles of 2-hydroxynaphthalene per equivalent of potassium base, dehydrating the mixture, adding carbon dioxide at about 20 to 90 psi at about 255°-280° C. and agitating and heating it at said pressure and temperature.
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