- Preparation method of 2 -bromo -4-chlorobenzaldehyde
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The invention relates to a preparation method of 2 -bromo -4-chlorobenzaldehyde and belongs to the field of medicinal chemistry. The preparation method can obtain 2 -bromo -4-chlorobenzaldehyde by taking nitrotoluene as a starting material through substitution, reduction, substitution, substitution, substitution, hydrolysis and elimination reaction. Compared with the prior art, the method shortens the reaction time, the reaction temperature is higher 120 °C or higher, the reaction conditions are mild, the yield of the obtained product is about 70% and more than 90%. The reaction temperature is reduced, high-boiling-point solvent is not needed to participate in the reaction, the post-treatment is simple, and the method is more suitable for industrial production with strict safety and environmental protection.
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Paragraph 0071-0073
(2021/08/25)
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- Nitration of deactivated aromatic compounds via mechanochemical reaction
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A variety of deactivated arenes were nitrated to their corresponding nitro derivatives in excellent yields under high-speed ball milling condition using Fe(NO3)3·9H2O/P2O5 as nitrating reagent. A radical involved mechanism was proposed for this facial, eco-friendly, safe, and effective nitration reaction.
- Wu, Jian-Wei,Zhang, Pu,Guo, Zhi-Xin
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supporting information
(2021/05/05)
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- Design, synthesis and anti-inflammatory activity of pyrimidine scaffold benzamide derivatives as epidermal growth factor receptor tyrosine kinase inhibitors
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Novel serious of pyrimidine scaffold benzamide derivatives (9 a-k) were synthesized and characterized by IR, HRMS, and NMR. Docking study of compounds 9 g, 9 h exhibited H-bonding interacts with Met769 into ATP binding site of EGFR-TK which showed similar binding mode to Lapitinib (PDB code: 1M17). Results indicated the ability to potent and selective inhibitors of the Epidermal Growth Factor Receptor tyrosine kinase (EGFR-TK). The molecular electrostatic potential (MEP), frontier molecular orbitals (FMOs) and HOMO-LUMO energy gap of the title compounds were investigated by using the B3LYP/6-31G method. The synthesized compounds were screened for in vitro anti-inflammatory activity.
- Thirumurugan,Lakshmanan, Sivalingam,Govindaraj, Dharman,Daniel Prabu, D. Sam,Ramalakshmi,Arul Antony
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p. 541 - 550
(2018/06/20)
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- Design, Synthesis, and Evaluation of the Kinase Inhibition Potential of Pyridylpyrimidinylaminophenyl Derivatives
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In view of potent kinase inhibitors for the treatment of myriad human disorders, we synthesized some structurally variant amide/cyclic amide derivatives based on pyridylpyrimidinylaminophenyl amine, the key pharmacophore of the kinase inhibitor drug molecule, imatinib, and evaluated their kinase inhibition potency. Among the various synthesized amides, compound 20, a cyclic amide/pyridin-2(1H)-one derivative, exhibited an IC50 value comparable to that of the drug imatinib against c-Src kinase, and another compound (14) containing a 2-((4-methyl-2-oxo-2H-chromen-6-yl)oxy)acetamide demonstrated an IC50 value of 8.39 μM. Furthermore, the constitution of the cyclic amide derivative was confirmed by the single-crystal X-ray diffraction technique. These results may serve as a gateway for developing novel next-generation kinase inhibitors.
- Manchanda, Priyanka,Parshad, Badri,Kumar, Amit,Tiwari, Rakesh K.,Shirazi, Amir N.,Parang, Keykavous,Sharma, Sunil K.
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- Reactivity of alkali and alkaline earth metal tetrafluorobromates towards aromatic compounds and pyridine
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The bromination activity of tetrafluorobromates of alkali and alkali-earth metals increases in the order KBrF4, CsBrF4, RbBrF4and Ba(BrF4)2. The most active tetrafluorobromate—Ba(BrF4)2is able to selectively brominate the deactivated aromatic compounds nitrobenzene and 4-nitrotoluene, but not the activated compounds benzene and toluene. In all cases bromination of methyl groups of methylbenzenes does not occur. Ba(BrF4)2forms the known complex C6H5N·BrF3when reacted with pyridine. Due to dilution by inert BaF2, this pyridine-based complex is air stable and can be considered as safer and more convenient reagent in comparison with the original fluorobromates; it can selectively brominate benzene and toluene in contrast with tetrafluorobromates.
- Sobolev, Vasily I.,Filimonov, Victor D.,Ostvald, Roman V.,Radchenko, Vyacheslav B.,Zherin, Ivan I.
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p. 120 - 123
(2016/11/17)
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- Tribromoisocyanuric acid in trifluoroacetic acid: An efficient system for smooth brominating of moderately deactivated arenes
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Moderately deactivated arenes are efficiently brominated by the reaction with tribromoisocyanuric acid (0.34 mol equiv) in trifluoroacetic acid at room temperature in 48-85% isolated yield. This medium avoids the polybromination of the substrate, observed in the same reaction performed in 98% H 2SO4. Georg Thieme Verlag Stuttgart · New York.
- De Almeida, Leonardo S.,De Mattos, Marcioc. S.,Esteves, Pierre M.
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p. 603 - 606
(2013/04/10)
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- Thallium(III) oxide as an oxidative reagent in organic chemistry
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Oxidative properties of thallium(III) oxide in various organic reactions were studied. Oxidative bromination of organic compounds in Tl2O 3-KBr-trifluoroacetic acid system was carried out. New synthetic method for preparation of diphenylthallium salts from phenylhydrazine and thallium(III) oxide was developed.
- Gun'kin
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experimental part
p. 451 - 454
(2010/08/04)
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- A facile total synthesis of imatinib base and its analogues
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Imatinib and its analogues were successfully synthesized by an improved method in 19.5-46.2% total yield of six main steps. Pyrimidinyl amine was prepared by the reaction of enaminone and guanidine nitrate without the use of a toxic cyanamide. N-(2-Methyl-5-nitrophenyl)-4-(pyridin-3-yl) pyrimidin-2-amine as a key intermediate for the synthesis of imatinib was prepared by coppercatalyzed iV-arylation of heteroarylamme in 82% yield. The copper salts were used instead of the expensive palladium compounds in this C-N bond-forming reaction. The intermediate nitro compound was reduced by a N2H 4.H2O/FeCl3/C system using water as a solvent in good yield.
- Liu, Yi-Feng,Wang, Cui-Ling,Bai, Ya-Jun,Han, Ning,Jiao, Jun-Ping,Qi, Xiao-Li
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p. 490 - 495
(2013/01/03)
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- Electronic effects of ring substituents on triplet benzylic biradicals
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UV irradiation of α-(o-alkylphenyl)acetophenones with a methoxy or cyano substituent para to the o-alkyl group of the α-aryl ring has revealed that a methoxy group slightly increases the stereoselectivity but not the quantum yield of indanol formation, whereas a cyano group greatly lowers both diastereoselectivity and quantum efficiency, confirming the likelihood that hydrogen-bonding of the hydroxy group to the α-phenyl ring plays an important role in the cyclization of the photogenerated triplet 1,5-biradical intermediates.
- Wagner, Peter J.,Wang, Lingling
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p. 645 - 647
(2007/10/03)
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- Reaction of dimethyldioxirane with aniline hydrohalides
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Oxidation of aromatic amine hydrohalides (aniline hydrochloride, hydrobromide, and hydrofluoride; 4-methylaniline hydrochloride and hydrobromide; 3-methylaniline and N,N-diethylaniline hydrochlorides) with dimethyldioxirane was studied. The product composition was analyzed in relation to the reactant ratio.
- Ivanova,Grabovskii,Kabal'nova,Shereshovets
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p. 2101 - 2105
(2007/10/03)
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- A novel method for the nitration of simple aromatic compounds
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Simple aromatic compounds such as benzene, alkylbenzenes, halogenobenzenes, and some disubstituted benzenes are nitrated in excellent yields with high regioselectivity under mild conditions using zeolite β as a catalyst and a stoichiometric quantity of nitric acid and acetic anhydride. The zeolite can be recycled, and the only byproduct is acetic acid, which can be separated easily from the nitration product by distillation; the process is inexpensive and represents an attractive method for the clean synthesis of a range of nitroaromatic compounds. For example, nitration of toluene gives a quantitative yield of mononitrotoluenes, of which 79% is 4-nitrotoluene; fluorobenzene gives a quantitative yield of mononitro compounds, of which 94% is 4-nitrofluorobenzene; and 2-fluorotoluene gives a 96% yield of mononitro products, of which 90% is the 5-nitro isomer and 10% is the 4-nitro isomer.
- Smith, Keith,Musson, Adam,DeBoos, Gareth A.
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p. 8448 - 8454
(2007/10/03)
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- Halogenation Using N-Halogenocompounds. II. Acid Catalyzed Bromination of Aromatic Compounds with 1,3-Dibromo-5,5-dimethylhydantoin
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Ring bromination of aromatic compounds using 1,3-dibromo-5,5-dimethylhydantoin in dichloromethane is promoted by the addition of strong acids.Both organic and inorganic acids whose pKa values are lower than -2 showed the promoting effect.This acid-catalyzed bromination is both practical and effective, even for aromatics having electron-withdrawing substituents.
- Eguchi, Hisao,Kawaguchi, Hideichiro,Yoshinaga, Sachiyo,Nishida, Akiko,Nishiguchi, Takeshi,Fujisaki, Shizuo
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p. 1918 - 1921
(2007/10/02)
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- CATALYTIC AND STOICHIOMETRIC BROMINATION OF AROMATIC COMPOUNDS IN AQUEOUS TRIFLUOROACETIC ACID IN THE PRESENCE OF NITROGEN-CONTAINING OXIDIZING AGENTS
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The mono- and polybromination of benzene, halogenobenzenes, toluene, p-xylene, anisole, biphenyl, benzotrifluoride, benzoic acid, p-nitro- and p-carboxytoluene, p-methoxybenzonitrile, tetralin, and naphtalene were studied in trifluoroacetic acid and its aqueous solutions in systems containing stoichiometric amounts of bromine or alkali-metal bromide and stoichiometric or catalytic (in the presence of oxygen or air) amounts of nitrogen-containing oxidizing agent (nitrogen(IV) oxide, alkali-metal nitrate or nitrite).It is suggested that the brominating agent under the investigated conditions is nitryl bromide NO2Br.Under the conditions of catalytic bromination anthracene is oxidized to anthraquinone with a preparative yield.
- Cheprakov, A. V.,Makhon'kov, D. I.,Rodkin, M. A.,Beletskaya, I. P.
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p. 217 - 223
(2007/10/02)
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- OXIDATION BY THE SALTS OF METALS. IV. OXIDATIVE HALOGENATION OF TOLUENE AND PARA-SUBSTITUTED TOLUENES WITH ELECTRON-WITHDRAWING GROUPS PROMOTED BY CERIUM(IV) SALTS IN AQEOUS SOLUTIONS OF TRIFLUOROACETIC ACID
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The oxidation of toluene and para-substituted toluenes with electron-withdrawing groups (para-toluic acid, methyl para-toluate, and para-nitrotoluene) by ammonium cerium(IV) nitrate and ammonium cerium(IV) sulfate was investigated in aqueous solutions of trifluoroacetic acid in the presence of alkali-metal chlorides and bromides.The rate and selectivity of oxidative halogenation in the side chain and/or aromatic ring under the investigated conditions depends strongly both on the nature of the substrate and the halide ion and on the reaction conditions and the ligand environment of the cerium(IV) atom.The oxidation of nitrotoluene takes place only in the presence of the bromide-containing systems and leads to the production of 4-nitrobenzyl bromide.For the other substrates halogenation in the aromatic ring can be realized with yields close to quantitative with ammonium cerium(IV) nitrate as oxidizing agent in concentrated aqueous solutions of trifluoroacetic acid (10 vol.percent of water).It was shown that the halogenating agents in this case are mainly the products from oxidation of the halide ions by the nitronium ions formed in the strongly acidic medium from the nitrate ions contained in the ammonium cerium(IV) nitrate.Bromination of the substituted toluenes in the presence of ammonium cerium(IV) sulfate and in the ammonium cerium(IV) nitrate-alkali-metal bromide systems with more than 10 vol.percent of water takes mainly in the side chain and can be used as a method for the production of 4-substituted benzyl halides with preparative yields.The effect of the composition of the solvent and the ratio of the oxidizing agent and alkali-metal halide on the rate and selectivity of oxidative bromination was studied.Possible reaction mechanisms are discussed.
- Makhon'kov, D.I.,Cheprakov, A.V.,Rodkin, M.A.,Mil'chenko, A.Yu.,Beletskaya, I.P.
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- LITHIATION OF SOME 3THIOPHENES AND INTRAMOLECULAR TRANSMETALATION
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The reaction of some halo-1-(thienyl)-2-phenylethanes such as 3-(2-phenylethyl)thiophene (1), 3-thiophene (2), 4--2-methylthiophene (3) and 4--2-chlorothiophene (4) with butyllithium and lithium diisopropylamide (LDA) under various conditions has been investigated.Competition between halogen-metal exchange in the benzene ring and metalation of thiophene ring was observed and an intramolecular transmetalation reaction was found.
- Gronowitz, Salo,Stenhammar, Karin,Svensson, Leif
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p. 947 - 959
(2007/10/02)
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- Electrophilic aromatic substitution. Part 24. The nitration of isopropylbenzene, 2- and 4-isopropyltoluene, 1-chloro-4-isopropylbenzene, 4-isopropylanisole, and 2-bromotoluene: Nitrodeisopropylation
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The kinetics and products of nitration in aqueous sulphuric acid of the title compounds have been studied. 4-Isopropyl-phenol and -anisole are nitrated at or near the encounter rate. In 65-79% H2SO4 2-isopropyltoluene suffers ca. 25% ipso-attack; the only fate of W iPri (ipso-Wheland intermediate) is nitrodeisopropylation. From 4-isopropyltoluene WiPri is also nitrodeisopropylated, but some 1,2-nitro-migration may occur. From the same compound WiMe may be captured by water, rearrange, or give 4-methylacetophenone; a mechanism is proposed for the formation of the last compound. Nitrodeisopropylation occurs without the assistance of water. With 4-isopropylanisole, demethoxylation and nitrodeisopropylation are consequences of the formation of WiPri. The results are consistent with increasing attack at C-4 with increasing acidity, loss of isopropyl without assistance from water, and decomposition of the unobserved intermediate, 4-isopropyl-4-nitrocyclohexa-2,5-dienone, by two processes. One, acid-catalysed process gives 4-nitrophenol and possibly 4-isopropyl-2-nitrophenol. The other, probably radical, process gives 4-isopropyl-2-nitrophenol. In contrast to 4-bromotoluene, 2-bromotoluene is not nitrodebrominated.
- Manglik, Ajay K.,Moodie, Roy B.,Schofield, Kenneth,Tobin, Geoffrey D.,Coombes, Robert G.,Hadjigeorgiou, Panicos
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p. 1606 - 1616
(2007/10/02)
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