705-29-3Relevant academic research and scientific papers
Synthesis method of 1-phenyl-3-(3-trifluoromethylphenyl)-2-acetone
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Paragraph 0005; 0010; 0011-0013, (2021/11/21)
The invention belongs to the technical field of chemical intermediates, and particularly relates to a synthesis method of 1-phenyl-3-(3-trifluoromethylphenyl)-2-acetone. A compound A is used as a basic raw material, and 1-phenyl-3-(3-trifluoromethylphenyl)-2-acetone is obtained through Blanc chloromethylation, substitution reaction, Claisen ester condensation and hydrolysis reaction in sequence. The synthesis method of 1-phenyl-3-(3-trifluoromethylphenyl)-2-acetone is high in purity, high in yield and simple to operate.
Method for synthesizing m-trifluoromethyl benzyl chloride through continuous flow
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Paragraph 0044-0107, (2021/08/06)
The invention provides a method for synthesizing m-trifluoromethyl benzyl chloride through continuous flow, belonging to the technical field of organic synthesis and application thereof. The method comprises the following steps: step 1, dissolving formaldehyde or a polymer thereof in trifluoromethyl benzene to prepare an organic solution; step 2, adding a chlorinating agent and a phase transfer catalyst into inorganic acid for dissolving to prepare an acid solution; and step 3, introducing the organic solution in the step 1 and the acid solution in the step 2 into a continuous-flow reactor for a reaction so as to obtain m-trifluoromethyl benzyl chloride. The method is simple and convenient to operate, good in selectivity, high in reaction rate and few in by-products, and the prepared m-trifluoromethyl benzyl chloride is excellent in yield and purity. Meanwhile, in a production process, the method is friendly to environment, high in safety, low in cost, stable during amplified production and suitable for industrial amplified production. The synthesis method disclosed by the invention has the characteristics of safety, high efficiency, high quality and low cost, so the synthesis method has huge practical value.
Preparation method of 3-trifluoromethylphenylacetonitrile
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Paragraph 0007; 0033; 0036, (2017/08/27)
The invention discloses a preparation method of 3-trifluoromethylphenylacetonitrile; 3-trifluoromethylbenzyl chloride is synthesized from trifluoromethyl benzene, tripolyformaldehyde, sulfuric acid and thionyl chloride under the action of the catalyst and is cyanided with sodium cyanide under the action of a phase transfer catalyst to obtain 3-trifluoromethylphenylacetonitrile; the preparation method is simple and is high in yield, produced wastewater is recyclable, environmental pollution is greatly reduced, reaction with the catalysts is faster, reaction temperature is lower, equipment corrosion due to side reaction where products are decomposed into HF is reduced, and the method is easy to industrialize.
Continuous-Flow Multistep Synthesis of Cinnarizine, Cyclizine, and a Buclizine Derivative from Bulk Alcohols
Borukhova, Svetlana,Nol, Timothy,Hessel, Volker
, p. 67 - 74 (2016/01/16)
Cinnarizine, cyclizine, buclizine, and meclizine belong to a family of antihistamines that resemble each other in terms of a 1-diphenylmethylpiperazine moiety. We present the development of a four-step continuous process to generate the final antihistamines from bulk alcohols as the starting compounds. HCl is used to synthesize the intermediate chlorides in a short reaction time and excellent yields. This methodology offers an excellent way to synthesize intermediates to be used in drug synthesis. Inline separation allows the collection of pure products and their immediate consumption in the following steps. Overall isolated yields for cinnarizine, cyclizine, and a buclizine derivative are 82, 94, and 87 %, respectively. The total residence time for the four steps is 90 min with a productivity of 2 mmol h-1. The incredible bulk: Bulk alcohols are converted continuously into chlorides using HCl in a microflow. A reaction network that consists of four steps and two inline separations leads to the continuous preparation of cinnarizine, cyclizine, and a buclizine derivative with yields of 82, 94, and 87 %, respectively. The total residence time for the four steps is 90 min with a productivity of 2 mmol h-1.
Synthesis and antiparasitic and antitumor activity of 2,4-diamino-6- (arylmethyl)-5,6,7,8-tetrahydroquinazoline analogues of piritrexim
Rosowsky, Andre,Papoulis, Andrew T.,Forsch, Ronald A.,Queener, Sherry F.
, p. 1007 - 1017 (2007/10/03)
Nineteen previously undescribed 2,4-diamino-6-(arylmethyl)-5,6,7,8- tetrahydroquinazolines (5a-m, 10-12) were synthesized as part of a larger effort to assess the therapeutic potential of lipophilic dihydrofolate reductase (DHFR) inhibitors against opportunistic infections of AIDS. Condensation of appropriately substituted (arylmethyl)triphenylphosphoranes with 4,4-ethylenedioxycyclohexanone, followed by hydrogenation (H2/Pd-C) and acidolysis, yielded the corresponding 4-(arylmethyl)cyclohexanones, which were then condensed with cyanoguanidine to form the tetrahydroquinazolines. Three simple 2,4-diamino-6-alkyl-5,6,7,8-tetrahydroquinazoline model compounds (9a-c) were also prepared in one step from commercially available 4-alkylcyclohexanones by this method. Enzyme inhibition assays against rat liver DHFR, Pneumocystis carinii DHFR, and the bifunctional DHFR-TS enzyme from Toxoplasma gondii were carried out, and the selectivity ratios IC50(rat)/IC50(P. carinii) and IC50(rat)/IC50(T. gondii) were compared. The three most potent inhibitors of P. carinii DHFR were the 2,5- dimethoxybenzyl (5j), 3,4-dimethoxybenzyl (5k), and 3,4,5-trimethoxybenzyl (51) analogues, with IC50 values of 0.057, 0.10, and 0.091 μM, respectively. The remaining compounds generally had IC50 values in the 0.1- 1.0 μM range. However all the compounds were more potent against the rat liver enzyme than the P. carinii enzyme and thus were nonselective. The T. gondii enzyme was always more sensitive than the P. carinii enzyme, with most of the analogues giving IC50 values of 0.01-0.1 μM. Moderate 5-10-fold selectivity for T. gondii versus rat liver DHFR was observed with five compounds, the best combination of potency and selectivity being achieved with the 2-methoxybenzyl analogue 5d, which had an IC50 of 0.014 μM and a selectivity ratio of 8.6. One compound (51) was tested for antiproliferative activity against P. carinii trophozoites in culture at a concentration of 10 μg/mL and was found to completely suppress growth over 7 days. The suppressive effect of 51 was the same as that of trimethoprim (10 μg/mL) + sulfamethoxazole (250 μg/mL), a standard clinical combination for the treatment of P. carinii pneumonia in AIDS patients. Four compounds (5a,h,k,l) were tested against T. gondii tachyzoites in culture and were found to have a potency (IC50 = 0.1-0.5 μM) similar to that of pyrimethamine (IC50 = 0.69 μM), a standard clinical agent for the treatment of cerebral toxoplasmosis in AIDS patients. Compound 5h was also active against T. gondii infection in mice when given qdx8 by peritoneal injection at doses ranging from 62.5 (initial dose) to 25 mg/kg. Survival was prolonged to the same degree as with 25 mg/kg clindamycin, another widely used drug against toxoplasmosis. Three compounds (5j-l) were tested for antiproliferative activity against human tumor cells in culture. Among the 25 cell lines in the National Cancer Institute panel for which data were confirmed in two independent experiments, the IC50 for at least two of these compounds was 50 of 50 was 0.01 μM.
