938-46-5

Usage

Preparation

Preparation by Fries rearrangement of quinol dipropionate (hydroquinone dipropionate),with aluminium chloride without solvent at 130–140° for 4 h (75%), ? at 142° for 30 min (80%), at 160–165° for 3 h (good yields) or at 190–200° for 90 min (60%) by using various quantities of aluminium chloride at 180° for 2 h (to see ? below) with aluminium chloride (2 equiv) in nitromethane at 20° for a week (7%) ? or in nitrobenzene (24%) with boron trifluoride complex (BF? 3-OBu2) at reflux for 1 h (42%) by using titanium tetrachloride (2 equiv) at 130° for 2 h gave only 6% yield Also obtained by treatment ofhydroquinone dipropionate with aluminium chloride in the presence of hyd-? roquinone (61%) 2-hydroxy-5-(propionyloxy)propiophenone with aluminium chloride (5 equiv) ? at 180° for 30 min in the presence of hydroquinone (57%) Also obtained by acylation of hydroquinone with propionic acidin the presence of boron trifluoride in ethylene dichloride at 50–55° (59%) ?, in tetrachloroethane at 90–95° for 5 h (70%) or at 50° for 4 h (70%) or without solvent (67%) at 80° for 2 h (54%) or at 125° for 2 h (71%) in the presence of zinc chloride at 190° few min (Nencki reaction) in the presence of 70% perchloric acid at reflux for 1 h (12%) Also obtained by Friedel–Crafts acylation of hydroquinone with propionyl chlo-ride in nitrobenzene in the presence of aluminium chloride (40%) Also obtained from 2-hydroxy-5-(propionyloxy)propiophenone; the ester group elimination on hydrolysis with 85% sulfuric acid at r.t. or by treatment with by aluminium chloride Also obtained by reaction of benzoquinone (2.5 equiv) with 2-oxobutanoic acid in aqueous acetonitrile or an acetonitrile/methylene chloride mixture (91%).

Upstream product

• 7402-28-0 hydroquinone dipropionate ester 
• 13098-94-7 Propansaeure-(4-methoxyphenyl)ester 
• 79-03-8 propionyl chloride 
• 123-31-9 hydroquinone 
• 150-78-7 1,4-dimethoxybezene 
• 802294-64-0 propionic acid 
• 600-18-0 2-Oxobutyric acid 
• 106-51-4 p-benzoquinone 
• 123-38-6 propionaldehyde 

Downstream Products

• 49710-99-8 1-(2-hydroxy-5-methoxyphenyl)-1-propanone 
• 140439-50-5 5'-<(6-chlorohexyl)oxy>-2'-hydroxypropiophenone 
• 140439-47-0 C₂₃H₁₈O₅ 
• 4693-31-6 2-Propylhydroquinone 
• 956-23-0 1-[5-(2,3-Dihydroxy-propoxy)-2-hydroxy-phenyl]-propan-1-one 
• 29026-02-6 1-(5-Allyloxy-2-hydroxy-phenyl)-propan-1-one 
• 79521-07-6 methyl 5,5'<2-(1-propenyl)-1,4-phenylenebis(oxy)>bis<2,2-dimethylpentanoate> 
• 79521-18-9 5,5'-[2-(1-hydroxypropyl)-1,4-phenylenebis(oxy)]bis[2,2-dimethylpentanoic acid] 
• 79521-06-5 dimethyl 5,5'-[[2-(1-hydroxypropyl)-1,4-phenylene]bis(oxy)]bis[2,2-dimethylpentanoate] 

Relevant academic research and scientific papers

Synthesis and pharmacological evaluation of acylhydroquinone derivatives as potent antiplatelet agents

Platelets are the smallest blood cells, and their activation (platelet cohesion or aggregation) at sites of vascular injury is essential for thrombus formation. Since the use of antiplatelet therapy is an unsolved problem, there are now focused and innovative efforts to develop novel antiplatelet compounds. In this context, we assessed the antiplatelet effect of an acylhydroquinone series, synthesized by Fries rearrangement under microwave irradiation, evaluating the effect of diverse acyl chain lengths, their chlorinated derivatives, and their dimethylated derivatives both in the aromatic ring and also the effect of the introduction of a bromine atom at the terminus of the acyl chain. Findings from a primary screening of cytotoxic activity on platelets by lactate dehydrogenase assay identified 19 non-toxic compounds from the 27 acylhydroquinones evaluated. A large number of them showed IC50 values less than 10 μM acting against specific pathways of platelet aggregation. The highest activity was obtained with compound 38, it exhibited sub-micromolar IC50 of 0.98 ± 0.40, 1.10 ± 0.26, 3.98 ± 0.46, 6.79 ± 3.02 and 42.01 ± 3.48 μM against convulxin-, collagen-, TRAP-6-, PMA- and arachidonic acid-induced platelet aggregation, respectively. It also inhibited P-selectin and granulophysin expression. We demonstrated that the antiplatelet mechanism of compound 38 was through a decrease in a central target in human platelet activation as in mitochondrial function, and this could modulate a lower response of platelets to activating agonists. The results of this study show that the chemical space around ortho-carbonyl hydroquinone moiety is a rich source of biologically active compounds, signaling that the acylhydroquinone scaffold has a promising role in antiplatelet drug research.

Synthesis and evaluation of aromatic methoxime derivatives against five postharvest phytopathogenic fungi of fruits. Main structure–activity relationships

The antifungal activity of a library of twenty-four aromatic methoximes was examined against five representative postharvest phytopathogenic fungi. The panel included Penicillium digitatum, Penicillium italicum, Rhizopus stolonifer, Botrytis cinerea and Monilinia fructicola, all of which cause relevant economic losses worldwide as a result of affecting harvested fruits. The minimum inhibitory concentrations and minimum fungicidal concentrations of each compound were defined and the main structure–activity relationships were determined. Although other congeners were more potent, drug likeliness considerations pointed to the methoxime derived from 2,4-dihydroxypropiophenone as the compound with the most suitable profile. The morphology of the colonies of the fungal strains treated with the methoxime was examined microscopically and the compound was also tested in freshly harvested peaches and oranges, exhibiting promising control profiles in both fruits, similar to those of the commercial agents Imazalil and Carbendazim.

An acylhydroquinone derivative produces OXPHOS uncoupling and sensitization to BH3 mimetic ABT-199 (Venetoclax) in human promyelocytic leukemia cells

Since cancer cells have different mitochondrial bioenergetic requirements than non-cancerous cells, therapeutic inhibition of its mitochondrial functionality continues to be an important target for anticancer drug discovery. In this study, a series of acylhydroquinones with different acyl-chain length, and their chlorinated derivatives, in the aromatic ring, synthesized by Fries rearrangement under microwave irradiation, were evaluated for their anticancer activity in two leukemia cell lines. Findings from the primary and secondary screening of the 18 acylhydroquinones, tested at 5 μM on acute promyelocytic leukemia HL-60 and acute lymphoblastic leukemia CEM cells lines, identified an acylchlorohydroquinone (12) with a highly selective anti-proliferative effect toward HL-60 cells. This compound induced S-phase arrest in the cell cycle progression of HL-60 cells with insignificant toxicity on leukemic CEM cells and non-cancerous Hs27 cells. In HL-60 leukemic cells, 12 triggered increased mitochondrial NADH oxidation, increased respiration in presence of oligomycin (state 4o), mitochondrial depolarization, and ROS production, suggesting an uncoupling of OXPHOS. This provoked a metabolic adaptation dependent on AMPK/ACC/autophagy axis, having the mitochondrial β-oxidation a pro-survival role since the combination of 12 and etomoxir, a carnitine palmitoyl-transferase (CPT) inhibitor promoted extensive HL-60 cell death. Finally, 12-induced metabolic stress sensitized to HL-60 cells to cell death by the FDA-approved anti-leukemic drug ABT-199, a BH3 mimetic. Therefore, our results suggest that acylchlorohydroquinone is a promising scaffold in anti-promyelocytic leukemia drug research.

Assessing parameter suitability for the strength evaluation of intramolecular resonance assisted hydrogen bonding in O-carbonyl hydroquinones

Intramolecular hydrogen bond (IMHB) interactions have attracted considerable attention due to their central role in molecular structure, chemical reactivity, and interactions of biologically active molecules. Precise correlations of the strength of IMHB’s with experimental parameters are a key goal in order to model compounds for drug discovery. In this work, we carry out an experimental (NMR) and theoretical (DFT) study of the IMHB in a series of structurally similar o-carbonyl hydroquinones. Geometrical parameters, as well as Natural Bond Orbital (NBO) and Quantum Theory of Atoms in Molecules (QTAIM) parameters for IMHB were compared with experimental NMR data. Three DFT functionals were employed to calculated theoretical parameters: B3LYP, M06-2X, and ωB97XD. O . . . H distance is the most suitable geometrical parameter to distinguish among similar IMHBs. Second order stabilization energies ?Eij(2) from NBO analysis and hydrogen bond energy (EHB) obtained from QTAIM analysis also properly distinguishes the order in strength of the studied IMHB. ?Eij(2) from NBO give values for the IMHB below 30 kcal/mol, while EHB from QTAIM analysis give values above 30 kcal/mol. In all cases, the calculated parameters using ωB97XD give the best correlations with experimental1H-NMR chemical shifts for the IMHB, with R2 values around 0.89. Although the results show that these parameters correctly reflect the strength of the IMHB, when the weakest one is removed from the analysis, arguing experimental considerations, correlations improve significantly to values around 0.95 for R2

Catalytic depolymerization of alkali lignin in subcritical water: Influence of formic acid and Pd/C catalyst on the yields of liquid monomeric aromatic products

Alkali lignin was subjected to depolymerization in subcritical water at 265 °C, 6.5 MPa for reaction times between 1-6 h in a batch reactor and in the presence of formic acid (FA) and Pd/C catalyst. The oil products were extracted into diethyl ether and contained >90% of single-ring phenolic compounds. The reaction of lignin in subcritical water alone yielded 22.3 wt% oil containing 56% guaiacol as the main product. A maximum oil yield of 33.1 wt% was obtained when the lignin was reacted in the presence of formic acid alone. In the presence of FA, catechol became the predominant compound, with more than 80% of the ether extract after 6 h. The conversion of guaiacol to catechol in the presence of formic acid suggested the hydrolysis of O-CH3 ether bonds. In addition, the yields of alkyl guaiacols increased in the presence of FA. The use of 5 wt% Pd/C catalyst with FA slightly decreased the yields of oil products but led to compounds indicative of hydrogenolysis of aryl-O ether bonds as well as hydrogenation of CC bonds.

An improved method for the preparation of 4,7-Dioxo-4,7-dihydrobenzo[b]thiophene-2-carboxylates from 2-acyl-1,4-benzoquinones and mercaptoacetates

4,7-Dioxo-4,7-dihydrobenzo[b]thiophene-2-carboxylates (4) have been synthesized in a one-pot procedure from 2-acyl-1,4-benzoquinones (1) and mercaptoacetates (2) by using 1-trimethylsilylimidazole as a protective reagent as well as a base. Thus, reaction of 1 with 2 in THF at room temperature was followed by treatment with excess of 1-trimethylsilylimidazole at 80°C. Then the cooled mixture was hydrolyzed with hydrochloric acid and oxidized with cerium(IV) ammonium nitrate (CAN) to give the expected thiophenequinone derivatives (4). 4,9-Dioxo-4,9-dihydronaphtho[2,3-b]thiophene-2-carboxylates (7) were similarly prepared from 2-acyl-1,4-naphthoquinones (5) and mercaptoacetates, in general, by omitting the CAN oxidation procedure.

Synthetic Utility and Mechanistic Implications of the Fries Rearrangement of Hydroquinone Diesters in Boron Trifluoride Complexes

Reactions of boron trifluoride methyl and ethyl etherate complexes with hydroquinone diesters yield monomethyl and monoethyl derivatives of acetylhydroquinones. The use of sterically hindered boron trifluoride etherate complexes results in acetylhydroquinone derivatives. This procedure represents a one-step synthesis of acetylhydroquinone derivatives, important building blocks for a variety of synthetic applications.

A direct route to acylhydroquinones from α-keto acids and α- carboxamido acids

The reaction of quinones with in situ generated acyl- or carboxamido radicals provides a direct rome to the synthesis of acylhydroquinones not accessible by the photochemical reaction of quinones with aldehydes.

Flavanone intermediates for halogenohydroxyflavones

Halogenohydroxyflavones STR1 in which R is alkyl having 1-3 C atoms, X is F, Cl, Br or I, and m, n and p are each 1, 2 or 3, and their esters with sulfuric acid and phosphoric acid, and the salts of these compounds, are suitable for the treatment of hyperthyroidism.