2107-76-8

Basic information

• Product Name: 5,7-Dihydroxy-4-methylcoumarin
• Synonyms: DIHYDROXY-4-METHYLCOUMARIN, 5,7-;4-METHYL-5,7-DIHYDROXYCOUMARIN;5,7-DIHYDROXY-4-METHYL-2H-CHROMEN-2-ONE;5,7-DIHYDROXY-4-METHYLCOUMARIN;5,7-dihydroxy-4-methyl-2h-1-benzopyran-2-on;5,7-dihydroxy-4-methyl-coumari;5,7-dihydroxy-4-methyl-2-benzopyrone;DIHYDROXY-4-METHYLCOUMARIN, 5,7-(RG)
• CAS NO: 2107-76-8
• Molecular Formula: C₁₀H₈O₄
• Molecular Weight: 192.17
• EINECS: 218-289-9
• Product Categories: Coumarins;Building Blocks;Heterocyclic Building Blocks;Building Blocks;Chemical Synthesis;Heterocyclic Building Blocks
• Mol File: 2107-76-8.mol
• Article Data: 125

Chemical Properties

• Melting Point: 296-299 °C(lit.)
• Boiling Point: 472.068 °C at 760 mmHg
• Flash Point: 197.851 °C
• Appearance: Yellow powder
• Density: 1.456 g/cm³
• Vapor Pressure: 1.55E-09mmHg at 25°C
• Refractive Index: 1.651
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 7.29±0.20(Predicted)
• Sensitive: Light Sensitive
• BRN: 179133
• CAS DataBase Reference: 5,7-Dihydroxy-4-methylcoumarin(CAS DataBase Reference)
• NIST Chemistry Reference: 5,7-Dihydroxy-4-methylcoumarin(2107-76-8)
• EPA Substance Registry System: 5,7-Dihydroxy-4-methylcoumarin(2107-76-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• TSCA: Yes
• HazardClass: IRRITANT
• Hazardous Substances Data: 2107-76-8(Hazardous Substances Data)

Usage

Chemical Properties

White metallic powder

Uses

5,7-Dihydroxy-4-methylcoumarin may be used in the synthesis of pyrano[2,3-h]coumarin derivatives and 5,7-dihydroxy-8-formyl-4-methylcoumarin.

General Description

Yellow powder. Fluoresces blue. Absorbs ultraviolet light.

Air & Water Reactions

Slightly water soluble .

Reactivity Profile

5,7-Dihydroxy-4-methylcoumarin is a phenol and lactone. Phenols do not behave as organic alcohols, as one might guess from the presence of a hydroxyl (-OH) group in their structure. Instead, they react as weak organic acids. Phenols and cresols are much weaker as acids than common carboxylic acids (phenol has Ka = 1.3 x 10^[-10]). These materials are incompatible with strong reducing substances such as hydrides, nitrides, alkali metals, and sulfides. Flammable gas (H2) is often generated, and the heat of the reaction may ignite the gas. Heat is also generated by the acid-base reaction between phenols and bases. Such heating may initiate polymerization of the organic compound. Phenols are sulfonated very readily (for example, by concentrated sulfuric acid at room temperature). The reactions generate heat. Phenols are also nitrated very rapidly, even by dilute nitric acid. Lactones react similarly to esters. Esters react with acids to liberate heat along with alcohols and acids. Strong oxidizing acids may cause a vigorous reaction that is sufficiently exothermic to ignite the reaction products. Heat is also generated by the interaction of esters with caustic solutions. Flammable hydrogen is generated by mixing esters with alkali metals and hydrides.

Fire Hazard

Flash point data for 5,7-Dihydroxy-4-methylcoumarin are not available. 5,7-Dihydroxy-4-methylcoumarin is probably combustible.

InChI:InChI=1/C10H8O4/c1-5-2-9(13)14-8-4-6(11)3-7(12)10(5)8/h2-4,11-12H,1H3

Upstream product

• 108-73-6 3,5-dihydroxyphenol 
• 75-36-5 acetyl chloride 
• 105-45-3 acetoacetic acid methyl ester 
• 3067-10-5 7-hydroxy-5-methoxychromene-2-one 
• 141-97-9 ethyl acetoacetate 
• 533-73-3 1,2,4-Trihydroxybenzene 
• 5394-63-8 2,2,6-trimethyl-4H-1,3-dioxin-4-one 
• 4341-76-8 Ethyl 2-butynoate 
• 66695-25-8 5,7-diacetyloxy-4-methyl-2H-chromen-2-one 
• 2732-18-5 5,7-dihydroxy-2H-chromen-2-one 
• 67-68-5 dimethyl sulfoxide 
• 674-82-8 4-methyleneoxetan-2-one 
• 4525-25-1 Methyl acetoacetate 

Downstream Products

• 111442-53-6 5-hydroxy-4-methyl-7-(toluene-4-sulfonyloxy)-coumarin 
• 6093-80-7 5,7-dimethoxy-4-methylcoumarin 
• 69830-33-7 4-methyl-5,7-bis-(toluene-4-sulfonyloxy)-coumarin 
• 102539-85-5 5,7,8-Trihydroxy-4-methyl-cumarin 
• 102539-84-4 5,6,7-Trihydroxy-4-methyl-cumarin 
• 106381-30-0 3-(3-formyl-2-hydroxy-4,6-dimethoxy-phenyl)-trans-crotonic acid 
• 108977-25-9 8-[(2,4-dinitro-phenylhydrazono)-methyl]-5,6,7-trimethoxy-4-methyl-coumarin 

Relevant articles and documents

Synthesis of coumarin derivatives in a microfluidic flow system employing the Pechmann condensation: A case study

For the synthesis of coumarin derivatives using the Pechmann condensation scheme, an acidic ionic liquid catalyst, abbreviated as [EBsImH][HSO4], was prepared from the ring opening of 1,4-butanesultone by 1-ethylimidazole, followed by the addition of 1 equiv. H2SO4(c). The [EBsImH][HSO4]-catalyzed Pechmann condensation reactions proceeded smoothly in a batch setup, with recyclable [EBsImH][HSO4] showing great catalytic activity. The acidic ionic liquid catalyst [EBsImH][HSO4] was recovered from EtOAc/H2O extraction of the product mixture, where the H2O layer was worked up and dried for reuse in consecutive runs of the Pechmann condensation reactions, maintaining >85% conversion for four times. The catalytic reactions were also carried out in a microfluidic flow setup. The flow parameters, the reactant molar amounts, and the additional H2SO4 as a modifying acid catalyst were optimized in the current case study. A minimum conversion rate of 2.8 g/hr of coumarin derivatives was demonstrated.

Sulfonated core-shell magnetic nanoparticle (Fe3O4@SiO2@PrSO3H) as a highly active and durable protonic acid catalyst; Synthesis of coumarin derivatives through pechmann reaction

Sulfonic acid supported silica coated magnetic nanoparticles (Fe3O4@SiO2@PrSO3H), was prepared by using low cost precursors and a facile immobilization technique. The final catalyst, which was characterized by XRD, FT-IR, vibrating sample magnetometer (VSM), TEM, and TGA techniques, was found to be an efficient and environmentally benign solid acid for the Pechmann condensation of substituted phenols with ethyl acetoacetate leading to the formation of coumarin derivatives. After the reaction, the catalyst could be effortlessly separated by external magnet and reused for 22 consecutive runs, without any significant loss in catalytic efficiency. The catalytic system presented offers a reusable strategy for the efficient synthesis of coumarin, simplicity in operation, and a green reaction profile by avoiding toxic conventional catalysts and solvents. Green earth and blue sky: Herein, we wish to disclose a simple bench top procedure for the synthesis of sulfonated core-shell magnetic nanoparticles (SMNPs) (Fe3O4@SiO2@PrSO3H) and discuss its performance as a very strong solid acid in the Pechmann condensation reaction.

Polyvinylpolypyrrolidone-bound boron trifluoride (PVPP-BF3); A mild and efficient catalyst for synthesis of 4-metyl coumarins via the Pechmann reaction

Polyvinylpolypyrrolidone-supported boron trifluoride has been studied for synthesis of 4-methyl coumarin by the Pechmann reaction. The reaction proceeded smoothly with hydroxyl phenols and ethyl acetoacetate in good yields in ethanol at reflux conditions. The polyvinylpolypyrrolidone-boron trifluoride complex is a non-corrosive and stable solid catalyst elevated Lewis acid property.

The Effects of Exposed Specific Facets and Sulfation on the Surface Acidity of Cu2O Solids

Cuprous oxide microcrystals with {111}, {111}/{100}, and {100} exposed facets were synthesized. 31P MAS NMR using trimethylphosphine as the probe molecule was employed to study the acidic properties of samples. It was found that the total acidic density of samples increases evidently after sulfation compared with the pristine cuprous oxide microcrystals. During sulfation, new {100} facets are formed at the expense of {111} facets and lead to the generation of two Lewis acid sites due to the different binding states of SO4 2? on {111} and {100} facets. Moreover, DFT calculation was used to illustrate the binding models of SO4 2? on {111} and {100} facets. Also, a Pechmann condensation reaction was applied to study the acidic catalytic activity of these samples. It was found that the sulfated {111} facet has better activity due to its higher Lewis acid density compared with the sulfated {100} facet.

Novel traceless liquid-phase synthesis of coumarin derivatives on poly(ethylene glycol) support

Coumarin derivatives were prepared by the von Pechmann reaction of PEG-bound acetoacetate reagent with phenols in the presence of TiCl4 in excellent yield and purity with a facile workup procedure. The polymer reagent could be recycled two to four times without diminishing the yield or purity. Copyright Taylor & Francis Group, LLC.

Periodic mesoporous silica chloride (PMSCl) as an efficient and recyclable catalyst for the Pechmann reaction

Periodic mesoporous silica chloride (PMSCl) with 2D P6mm hexagonal structure which can be prepared by a simple procedure is reported to act as an efficient and recyclable catalyst for the conversion of a variety of phenols into their corresponding coumarins through Pechmann reaction. The reactions were conducted under solvent-free conditions in good to excellent yields.

Sulphamic acid - An efficient and cost-effective solid acid catalyst for the pechmann reaction

Sulphamic acid (H2NSO3H, SA) is used as an alternative to conventional acid catalysts in the Pechmann condensation of phenols with β-ketoester leading to the formation of substituted coumarin. The method is simple, cost-effective, solvent-free and gives good yields in a short reaction time.

Dually activated organo- and nano-cocatalyzed synthesis of coumarin derivatives

A wide range of substituted coumarin derivatives were synthesized by refluxing in acetonitrile, ethyl acetoacetate, and ethyl benzoyl acetate with a wide range of structurally diverse phenol derivatives within a short reaction time with a catalytic combination of pyridine dicarboxylic acid as organocatalyst and nanocrystalline ZnO.

Synthesis and bioactive evaluation of a novel series of coumarinazoles

A series of novel coumarinazoles were designed, synthesized, and characterized by IR, NMR, MS and HRMS spectra. The bioactive assay for the newly prepared compounds against six bacteria and five fungi manifested that most new compounds exhibited good or even stronger antibacterial and antifungal activities in comparison with reference drugs Chloromycin, Norfloxacin and Fluconazole. Bis-azole alcohols 7a and 7d-e showed better anti-Candida utilis activity than mono-azole derivatives 4a and 4d-e at the tested concentrations, and they were more potent than the clinical Fluconazole. While triazole alcohol 7a gave comparable anti-Candida albicans and anti-Candida mycoderma activity to Fluconazole and better anti-MRSA activity than mono-triazole one 4a and clinical Norfloxacin. 1H-Benzoimidazol-2-ylthio coumarin derivatives 4e and 7e gave the strongest anti-Escherichia coli JM109 efficacy. Oxiran-2-ylmethoxy moiety was found to be a beneficial fragment to improve antibacterial and antifungal activity to some extent.

B(C6F5)3-catalyzed synthesis of coumarins via Pechmann condensation under solvent-free conditions

Tris(pentafluorophenyl)borane [B(C6F5)3] catalyzed simple, efficient and environmentally benign protocol has been developed for the Pechmann condensation using variety of phenols and β-ketoesters under solvent-free conditions to afford coumarin derivatives. The present protocol displayed significant advantages such as low catalyst loading, short reaction time, mild reaction conditions, low toxicity, easy work-up, high yields, and compatibility with other functional groups. In addition, it is a convenient, clean, and fast alternative approach for synthesizing variety of coumarin derivatives. Moreover, the applicability of this method towards large-scale synthesis demonstrated its suitability for the industrial application. Graphic abstract: [Figure not available: see fulltext.]

Design of a highly efficient and water-tolerant sulfonic acid nanoreactor based on tunable ordered porous silica for the von Pechmann reaction

(Figure Presented) Among a number of different sulfonic acid nanoreactors prepared, 5 having both acidic sites and phenyl groups located inside the mesochannels of SBA-15 was shown to be the most active and reusable catalyst in the von Pechmann reaction. The mesochannels, and covalently anchored organic groups, provide a synergistic means of an efficient approach of the reactants to acidic sites, enough space for the subsequent cyclization, and suitable hydrophobicity to drive out the water byproduct.

Synthesis of substituted coumarins catalyzed by sawdust-SO3H. An efficient and environmentally benign solid acid catalyst under solvent-free conditions

The sulfonated sawdust (SD-SO3H) was easily prepared by treatment of sawdust, a biomass waste material, with chlorosulfonic acid and characterized by elemental analysis, SEM and TGA. The bio-degradable solid acid catalyst has been applied to the Pechmann condensation reaction of phenols with β-ketoesters for the synthesis of coumarin derivatives under solvent-free conditions. This environmentally benign and inexpensive method has such advantages as simplicity in operation, high yields, low catalyst loading and short reaction time. The catalyst can be efficiently recycled with insignificant loss of activity.

Cux2 (x =cl, br) as catalysts for pechmann reaction: Synthesis of 4-substituted coumarins

CuX2 (X=Cl, Br) are found to be efficient catalysts (10 mol%) for the Pechmann condensation reaction of phenols and b-ketoesters to give 4-substituted coumarins under solvent-free conditions. The yields of coumarin derivatives obtained via this

Expeditious approach to coumarins via pechmann reaction catalyzed by molecular iodine or AgOTf

An efficient and facile route for the synthesis of coumarins via the Pechmann reaction catalyzed by molecular iodine or AgOTf was described. Copyright Taylor & Francis Group, LLC.

Acceleration of the Pechmann Reaction by Microwave Irradiation: Application to the Preparation of Coumarins

Substituted coumarins are synthesised from methyl acetoacetate and substituted phenols using microwaves in excellent yields.

Poly(4-vinylpyridine)-supported sulfuric acid: An efficient solid acid catalyst for the synthesis of coumarin derivatives under solvent-free conditions

Poly(4-vinylpyridine)-supported sulfuric acid is an efficient catalyst for the Pechmann condensation of acetoacetic esters with phenols, leading to the formation of coumarins in good yields within a few minutes under solvent-free microwave conditions. The catalyst used can be recovered and reused after activation. Springer-Verlag 2011.

Role of basicity, calcinations, catalytic activity and recyclability of hydrotalcite in eco-friendly synthesis of coumarin derivatives

An efficient and simple protocol is described for synthesis of coumarin derivatives using Mg-Al-CO3 and Ca-Al-CO3 hydrotalcite as an environmental friendly and reusable heterogeneous catalyst under solvent free conditions. The catalysts were characterized by Hammett titration, SEM and XRD data. Present study revealed that catalytic activity and basicity depend on compositions of hydrotalcite. The calcined hydrotalcite with an Mg/Al of 3:1 derived from calcinations at 750 K was found to be suitable catalyst that gives the highest basicity and the best catalytic activity for this reaction. Catalyst allows short reaction time, high catalytic activity, easy to work up and is reusable. Step economy, atom efficiency and solvent free conditions are some important salient features of this protocol.

Gallium triiodide-catalyzed organic reaction: A convenient procedure for the synthesis of coumarins

Gallium triiodide, which was generated in situ by the reaction of gallium metal and iodine, was used as an efficient catalyst in the Pechmann condensation of phenols with ethyl acetoacetate, leading to the formation of coumarins. The reaction proceeded in dichloromethane at room temperature with good to excellent yields. Copyright Taylor & Francis, Inc.

PEG-SO3H: A mild and efficient recyclable catalyst for the synthesis of coumarin derivatives

A simple and efficient synthesis of coumarin derivatives through condensation reaction of substituted phenols and dicarbonyl compounds using PEG-SO3H as a recyclable catalyst under solvent-free conditions is described.

Use of a highly efficient and recyclable solid-phase catalyst based on nanocrystalline titania for the pechmann condensation

Nanocrystalline titania-based sulfonic acid was used as an efficient and reusable catalyst for the synthesis of coumarins. The clean, mild acidity condition, the quantitative yields of products, the short reaction time, and the low reaction temperature are attractive features of this method, making it suitable for heat- or acid-sensitive substrates, particularly in drug synthesis. In practice, this method affords an advantageous combination of satisfactory yields, easy product isolation and purification.

Alum (KAl(SO4)2·12H2O) catalyzed one-pot synthesis of coumarins under solvent-free conditions

Alum (KAl(SO4)2·12H2O) is used as an efficient catalyst in the Pechmann condensation of phenol derivatives with β-keto esters leading to the formation of coumarins in excellent yields under solvent-free conditions. This methodology offers significant improvements for the synthesis of coumarins with regard to the yield of products, simplicity in operation, and green aspects by avoiding toxic catalysts and solvents.

Photo-stimulated self-healing polyurethane containing dihydroxyl coumarin derivatives

A novel polyurethane was synthesized, which consisted of isophorone diisocyanate, polyethylene glycol and photo-reversible moiety 5,7-bis(2-hydroxyethoxy)-4-methylcoumarin. By taking advantage of reversible photodimerization and photocleavage habit of coumarin, the polyurethane can be repeatedly crosslinked and de-crosslinked under successive UV irradiations at 350 and 254 nm. More importantly, damages in crosslinked version of the polyurethane can be re-bonded through chain reconnection on fracture surfaces resulting from the photochemical reactions, as characterized by mechanical strength restoration tests. Compared to the previous proof-of-concept trial with monohydroxyl coumarin derivatives as the photosensitive groups, the application of dihydroxyl coumarin derivatives in the present work prevented the undesirable gelation during synthesis and enabled properties-oriented structure adjustment of polymerization products. Besides, structure-performance relationship study of the polyurethane revealed that rubbery domains resulting from microphase separation were necessary for the photo-remending with high efficiency.

1-Nicotinoylbenzotriazole: A Convenient Tool for Site-Selective Protection of 5,7-Dihydroxycoumarins

1-Nicotinoylbenzotriazole (NicBt) was uncovered as an efficient protecting agent for the site-selective acylation of resorcinol-type phenolic groups with almost equal reactivity. The use of NicBt allows selective protection of the 7-OH group in 5,7-dihydr

Pegylated enzyme entrapped in poly(vinyl alcohol) hydrogel for biocatalytic application

A procedure for enzyme entrapment into matrices suitable for biocatalytic applications is reported. The method, which takes advantage of the stable formation of polyvinyl alcohol (PVA) hydrogels by freezing and thawing PVA aqueous solutions, was assayed using lipase as model enzyme. The leakage of lipase was minimised by using high molecular weight PVA and by previous conjugation of the enzyme to PEG. The immobilised PEG enzyme maintained its catalytic activity in organic solvents also, thus allowing enzymatic activity towards water insoluble substrates. The activity was largely increased reducing the diffusional constrain by cutting the matrices into slices of micron size. Matrix-entrapped lipase-PEG, when used in the hydrolysis of acetoxycoumarins, showed a conversion rate of about 10 times lower than the enzyme-PEG in the free form, and maintained regioselectivity when a diacetylated product was used as substrate.

Pentafluorophenylammonium triflate (PFPAT): An efficient, metal-free and reusable catalyst for the von Pechmann reaction

Pentafluorophenylammonium triflate (PFPAT) is used as an efficient catalyst in the von Pechmann condensation of phenols with β-ketoesters leading to the formation of coumarin derivatives. Short reaction times, easy and quick isolation of the products, excellent chemoselectivity, excellent yields and ease of catalyst recovery with consistent activity makes this protocol efficient and environmentally benign.

Multicomponent click polymerization for the synthesis of coumarin containing 1,4-polytriazoles and their application as dye adsorbent

The synthesis of heterocycle-based polymers have remained an important area of research in polymer chemistry. Herein we report a one-pot synthesis of a set of novel coumarin containing regioselective 1,4-polytriazols by multicomponent click polymerization using Cs2CO3 as a base and copper(I) acetate as a catalyst in DMF medium. In this one-pot process, O-alkylation followed by a three-component click reaction between the coumarin-linked dialkyne, sodium azide and alkyl/benzyl dibromides provide novel polymers having coumarin-triazole-linker (C-T-L) units. Ten novel polymers have been synthesized with high molecular weights (Mw = 20,080–46,340 g/mol) and very good yields (83–93%). All the polymers were well characterized by IR, NMR, and GPC. The dye removal capacities of these polymers were evaluated for methylene blue (MB), rhodamine B (RB), methyl orange (MO), and congo red (CR). Polymers P1, P2, and P3 showed very high affinity towards methylene blue dye and among them, P2 showed the highest dye removal efficiency (971 mg/g) for MB. The reusability of P2 was checked and found excellent removal efficiency (RE = 96%) up to the eighth cycle.

Preparation of a novel, efficient, and recyclable magnetic catalyst, Cu(II)-OHPC-Fe3O4 nanoparticles, and a solvent-free protocol for the synthesis of coumarin derivatives

Cu(II) supported on 5-oxo-4,5-dihydro-pyrrole-3-carboxylic acid functionalized Fe3O4 nanoparticles (Cu(II)-OHPC-Fe3O4) as a new magnetic nanocatalyst was prepared and characterized by ICP-AES, FT-IR, XRD, SEM, TEM, TGA, XRD, VSM and EDX techniques. Prepared nanocatalyst (Cu(II)-OHPC-Fe3O4) is employed for Pechmann reactions between different substituted phenols and ethyl acetoacetate to obtain new products of coumarin derivatives in good to excellent yields. This green catalyst was easily removed, reused several times with no significant loss of its activity and provided clean synthesis with excellent yield and reduced time.

Antagonistic activity of hydroxycoumarin-based antioxidants as possible singlet oxygen precursor photosensitizers

Coumarins are phenolic-type compounds with efficient antioxidant activity due to their ability to scavenge reactive oxygen species. Nevertheless, their ability to behave as photosensitizers capable of generating reactive oxygen species, such as singlet oxygen, has been less studied. In this work, the photosensitizing ability of seven hydroxycoumarins was evaluated through the photooxidation of ergosterol by quantifying the conversion of ergosterol into ergosterol peroxide. In our experimental conditions, we found that almost every tested antioxidant coumarin promotes the peroxidation of ergosterol. The results suggest that the hydroxycoumarins exhibit potential photosensitizing activity by promoting singlet oxygen generation by a Type II photochemical mechanism. Density functional theory (DFT) calculations were also performed to obtain further insight into the chemical reactivity of tested compounds; the observed tendency in the group of antioxidant coumarins to promote the reaction was their hardness due to the principle of maximum hardness. To evaluate our conclusion, we performed the reaction using a highly polarizable coumarin as a photosensitizer, which resulted in an increased photosensitizing capacity supported with DFT calculations, which reinforces our analysis. Finally, we found that hydroxycoumarins can be potentially pro-oxidants since some of them can act as photosensitizers and generate singlet oxygen in the presence of UV–Vis light, a characteristic that must be considered when these compounds are used as antioxidants.