Syntheses of 3-Chloro-7-[(Chlorocarbonyl)Methoxy]-4-Methylcoumarin

Two efficient syntheses of 3-chloro-7-[(chlorocarbonyl)methoxy]-4-methylcoumarin are described, one utilizing traditional chemistry starting from 3-chloro-7-hydroxy-4-methylcoumarin, while the other uses a novel reagent, sulfuryl chloride/thionyl chloride, in a one-pot reaction starting from 7-(carboxymethoxy)-4-methylcoumarin.     

Competitive methylation of some phenolic compounds

The competitive methylation of a mixture of 6-hydroxy-4-methylcoumarin and of 7-hydroxy-4-methylcoumarin and also of other compounds of phenolic nature has been studied. It had ben shown that in the presence of 1 mole of alkali, methylation of the more acidic hydroxyl takes place at the oxygen atom, and with 2 moles of alkali, the stronger conjugated base reacts.     

Synthesis and structure of indoline spiropyrans of the coumarin series

New indoline spiropyrans of the coumarin series were synthesized by the condensation of indoline and hydroxyformylcoumarin derivatives. Spiropyrans, viz., derivatives of 8-formyl-7-hydroxy-4-methylcoumarin and 5-formyl-6-hydroxy-4-methylcoumarin, under irradiation are transformed into open forms, which are recyclized in the dark. The compounds formed by the condensation of the indoline derivatives with 3-formyl-4-hydroxycoumarin have an open structure of the merocyanine dyes and are transformed into spiro forms neither in the dark nor under irradiation with the visible light. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2342–2349, October, 2005.     

Crystal structure of 7,8-dihydroxy-4-methylcoumarin.

The structure of 7,8-dihydroxy-4-methylcoumarin was determined by an X-ray diffraction method. The compound crystallized in the triclinic space group P1, Z = 2, with a = 7.631(2), b = 9.456(5), c = 7.075(3)A, alpha = 103.13(3), beta = 91.84(3), gamma= 68.21(3) degrees, and V= 460.9(3)A3. The X-ray crystal structure was also compared with those of 5,7-dihydroxy-4-methylcoumarin and 7-hydroxy-4-methylcoumarin.     

Two new coumarin glucosides biosynthesized by transgenic hairy roots of Polygonum multiflorum

The glycosylation of hydroxylcoumarin was investigated by using suspension cultures of hairy roots of Polygonum multiflorum. Two new coumarin glucosides （3 and 4） were biosysthesized by regioselectively glycosylation of corresponding substrates （1 and 2） in the system. The structures of two products were identified as 7-hydroxy-4-methylcoumarin 5-O-β-D-glucopyranoside and 7- hydroxy-3,4-dimethylcoumarin 5-O-β-D-glucopyranoside on the ground of chemical and spectroscopic methods, respectively. 2007 Rong Min Yu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.     

7-羟基-4-甲基-8-(4'-甲基哌嗪-1'-基)-亚甲基香豆素的光二聚行为

通过Mannich反应在7-羟基-4-甲基香豆素的8-位上引入具有pH响应性能的4-甲基哌嗪的供电子哌嗪基团, 得到水溶性香豆素衍生物, 7-羟基-4-甲基-8-(4'-甲基哌嗪-1'-基)-亚甲基香豆素(HMPC), 利用哌嗪环上的叔胺给电子体系对酸碱的敏感特性调节HMPC的光二聚反应特征. 详细考察该香豆素衍生物在不同pH水溶液中的紫外光二聚性能, 紫外光谱分析显示, 通过调节HMPC水溶液的酸碱性可有效改变其紫外特征吸收; 在波长大于310 nm的紫外光照射下, 衍生物上的香豆素单元可进行光二聚, 并且紫外点光源光二聚反应实验表明, 其在中性水溶液中的反应速度最快, 其次为碱性条件中的反应, 最慢的则是酸性条件中的反应.     

Synthesis and reversible photocleavage of novel polyurethanes containing coumarin dimer components

Six polyurethanes containing coumarin dimer components in the main chain have been prepared by polyaddition of diisocyanates with anti head-to-head 7-hydroxycoumarin dimer or anti head-to-tail 7-hydroxy-4-methylcoumarin dimer. 7-Acetoxycoumarin and 7-acetoxy-4-methylcoumarin were first prepared and then photodimerized under 350 nm UV light to give anti head-to-head 7-acetoxycoumarin dimer and anti head-to-tail 7-acetoxy-4-methylcoumarin dimer, respectively. After hydrolyzing under acidic conditions to 7-hydroxycoumarin dimer and anti head-to-head 7-hydroxycoumarin dimer, they were polymerized with aliphatic and aromatic diisocyanates in N,N-dimethylacetamide to give the polyurethanes. Addition of dibutyltin dilaurate (T-12) as catalyst increases the polymer yield with the viscosity remaining almost unchanged. It was also found that lithium chloride enhances both the yield and viscosity of the polyurethanes by increasing their solubility possibly through complexation. The polyurethanes are symmetrically photocleaved at cyclobutane rings under 254 nm UV light to dicoumarins. Reversible photodimerization of the photocleaved compounds have also been investigated under 300 and 350 nm UV light. The polyurethanes from aromatic diisocyanates or with 4-methyl substituent exhibit greater reactivity in the photocleavage reaction. © 1997 John Wiley & Sons, Inc.     

Effect of functional groups on the solubilities of coumarin derivatives in supercritical carbon dioxide

Summary Solubilities in supercritical CO₂ of coumarin, four monosubstituted coumarin derivatives (4-hydroxycoumarin, 7-hydroxycoumarin, 7-methoxycoumarin, and 7-methylcoumarin) and four disubstituted derivatives, (6,7-dihydroxycoumarin, 7-hydroxycoumarin-4-acetic acid, 7-methoxycoumarin-4-acetic acid, and 7-hydroxy-4-methylcoumarin) were measured in the temperature range 35–50 °C and the pressure range 8.5–25 MPa. In general, the substituted coumarin derivatives were less soluble than simple coumarin. It was also found that substitution at the C-4 position of coumarin tended to reduce the solubility more than substitution at the C-7 position. These solubility data are essential for the systematic application of SFE and SFC of coumarin derivatives from plant sources.     

Synthesis of the reported structure of crassiflorone, a naturally occurring quinone isolated from the African ebony Diospyros crassiflora, and regioisomeric pentacyclic furocoumarin naphthoquinones

A synthesis of the structure reported for the natural product crassiflorone, a furocoumarin naphthoquinone, is described. The key steps are a Diels-Alder reaction to form 2-bromo-8-hydroxy-6-methylnaphthoquinone, followed by O-protection and copper(II) mediated coupling to 4-hydroxy-5-methylcoumarin to establish the pentacyclic framework whose structure was unambiguously confirmed by X-ray crystallography. Since the spectroscopic data of the synthetic material did not match those reported for the natural product, three further regioisomeric furocoumarin naphthoquinones were prepared by copper(II) mediated coupling of 4-hydroxy-5- or 8-methyl coumarins with 5-benzyloxy-2-bromo-7-methyl- or 8-benzyloxy-2-bromo-6-methyl-1,4-naphthoquinone. Again the spectroscopic data did not match those of the natural material and therefore the true structure of crassiflorone remains unknown.     

Synthesis, characterization, biological and thermal behaviour of Co(II), Ni(II) and Cu(II) complexes with Schiff bases having coumarin moieties

A series of Co(II), Ni(II) and Cu(II) complexes have been synthesized with Schiff bases derived from 5-amino-1,3,4-thiadiazole-2-thiol and 8-formyl-7-hydroxy-4-methylcoumarin/8-acetyl-7-hydroxy-4-methylcoumarin. The chelation of the complexes has been proposed in the light of analytical, spectral (IR, UV–Vis), ESI-mass, magnetic, ESR and thermal studies. The measured molar conductance values indicate that the complexes are non-electrolytes. TG and DTA provide the useful information about the coordination of water molecules to the metal ion and the stability of the complexes. TG and DTA curves show that the Co(II) complexes decomposition takes place in two stages corresponds to loss due to water molecules and Schiff base moiety. Whereas, Ni(II) and Cu(II) complexes decomposition took place in three steps corresponding to the loss of coordinated water molecules, 1,3,4-thiadiazole moiety and coumarin moiety, respectively. The Schiff bases and their complexes have been screened for their antibacterial and antifungal activities. The results of these studies show the metal complexes to be more antibacterial and antifungal as compared to the uncomplexed coumarins.     

One-pot synthesis of coumarine derivatives using butylenebispyridinium hydrogen sulfate as novel ionic liquid catalyst

Pechmann condensation reaction of 3-hydroxyphenol and ethyl acetoacetate in the presence of 1,1′‐butylenebispyridinium hydrogen sulfate as an efficient, green, and recyclable catalyst produces 7-hydroxy-4-methylcoumarin in good yield under solvent-free conditions at room temperature. This catalyst has advantages such as the following: good to excellent yields, short reaction times, simplicity in operation, and easy workup procedure.     

Effect of some physico-chemical conditions on an immunoassay for viable Escherichia coli

Viable Escherichia coli can be detected by an immunoassay in which live bacteria captured on antibody-coated paramagnetic beads are induced to synthesize the enzyme β-galactosidase, which catalyzes the hydrolysis of the slightly fluorescent substrate 4-methyl umbelliferyl-β-d-galactoside to the highly fluorescent product 7-hydroxy-4-methylcoumarin for detection. The effects of bacterial strain, presence of dead bacteria, and some environmental stresses on assay performance were evaluated.     

Solvent-induced <Emphasis Type="Italic">E/Z</Emphasis>(C=N)-isomerization of imines of some hydroxy-substituted formylcoumarins

Aromatic imines, namely, 5-formyl-6-hydroxy-4-methyl- and 8-formyl-7-hydroxy-4-methylcoumarin derivatives, have been synthesized. A dependence of their spectral characteristics (¹H NMR spectra, electronic absorption spectra) from the solvent (DMSO, CHCl₃, DMF, acetonitrile, MeOH) has been studied. The solvatochromic effects observed for a number of imines, first of all, for 7-hydroxy-4-methyl-8-(4′-nitrophenylimino)methyl-2H-1-benzopyran-2-one, were related to their E/Z-isomerization with respect to the C=N bond based on the quantum chemical calculations by the AM1, PM3, PPP CI methods. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1954–1960, September, 2008.     

Reversible photodimerization of coumarin derivatives dispersed in poly(vinyl acetate)

Four photoreactive coumarin derivatives were successfully synthesized from 7-hydroxy-coumarin and 7-hydroxy-4-methylcoumarin, i.e., 7-propionyloxy-4-methylcoumarin (M₁), 7-palmitoyloxy-4-methylcoumarin (M₂), 7-propionyloxycoumarin (M₃), and 7-palmitoy-loxycoumarin (M₄). Reversible photodimerization (350 or 300 nm) and photocleavage (254 nm) of these coumarin derivatives dispersed in poly(vinyl acetate) (PVAc) were investigated by tracing their UV absorbance variations at 310 nm. The M₂ and M₄ with long palmitoyl chain show much better photoreaction reversibility than M₁ and M₃ with short propionyl chain. Moreover, photodimerization rate (under 350 nm) of M₂ is greater than 200 times of that of M₁. This has been explained by the formation of suitable conformation for revers-ible photodimerization due to the hydrophobic interactions. Photodimerization of M₂ is ca. 3 times quicker than that of M₄, indicating 4-methyl substitution enhances pho-todimerization. The influence of photodimerization wavelength (350 and 300 nm) and photosensitizer (benzophenone) have also been investigated in detail. © 1995 John Wiley & Sons. Inc.     

Intermolecular interactions in dioxane-water solutions of substituted coumarins according to ultrasonic data

Density, ultrasonic velocity of pure dioxane (Dx) and ligands, 4,6-dimethyl-7-hydroxycoumarin (L₁), 6-ethyl-7-hydroxy-4-methylcoumarin (L₂), and 3-chloro-7-hydroxy-4-methylcoumarin (L₃) in different percent of Dx-water mixture have been investigated at 303.15 K. Acoustical parameters such as adiabatic compressibility (β), intermolecular free length (L _f ), acoustical impedance (Z), relative association (R _A ), apparent molar compressibility (Φ_β), and apparent molar volume (Φ _V ) have also been evaluated from the experimental data of density and ultrasonic velocity. An excellent correlation between a given parameters is observed at all percent of dioxane-water and the result suggests nature of intermolecular interactions between the components.     

Photochromism of indoline spiropyrans of the coumarin series in polymeric matrices

The photochromic properties and aggregation processes of merocyanine forms of indoline spiropyrans of the coumarin series in the block and film poly(methyl methacrylate) (PMMA) were studied and compared by spectral and kinetic methods. Photochromism of the synthesized compounds depends on their structure. The efficient formation of J-aggregates was observed for indoline spiropyrans of the coumarin series based on 8-formyl-7-hydroxy-4-methylcoumarin and 3-formyl-4-hydroxycoumarin. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 870–875, May, 2007.     

α-环糊精修饰型香豆素的设计合成

以环氧氯丙烷为桥接,利用水溶性α-环糊精(α-CD)进行7-羟基-4-甲基香豆素的功能化修饰,得到新型α-环糊精修饰型香豆素衍生物(α-CD-C).用傅里叶变换红外(FT-IR)光谱、氢核磁共振(1H NMR)、液质联用(LC-MS)等对该香豆素衍生物进行了结构表征.紫外光二聚实验表明,该α-环糊精修饰型香豆素可在365 nm光照下进行光二聚反应,且可在随后的254 nm光照下进行解二聚反应;同时通过比较该交替光照下的光二聚反应程度,可知该光二聚反应仅是部分可逆的.     

Reactivity ratio of novel acrylic copolymer by NMR spectroscopy

The monomer 4-methylcoumarylacrylate (4-MCA) was synthesized from 7-hydroxy-4-methylcoumarin and characterized by conventional methods. Homo and copolymers of 4-methylcoumarylacrylate and styrene were synthesized with different feed ratios using N,N-dimethylformamide (DMF) as a solvent and 2,2′-azobisisobutyronitrile as an initiator at 70°C.The resulting polymers were characterized by infrared spectroscopy. Copolymer compositions were determined by nuclear magnetic resonance spectroscopy. The monomer reactivity ratios were determined by applying the conventional linearization method of Fineman–Ross and Kelen–Tudos. The reactivity ratios values of 4-methylcoumarylacrylate and styrene obtained from F–R plot are 1.36 and 0.62, respectively, and from K–T plot 1.24 and 0.58, respectively.     

Synthesis of 2-aryl-6-methyl-5-nitroquinoline derivatives as potential prodrug systems for reductive activation

A range of novel 2-aryl-5-nitroquinolines have been synthesised as potential prodrug systems for bioreductive activation. Thus 5-nitroquinoline underwent vicarious nucleophilic substitution at C-6 with bromoform anion to give, after hydrolysis and reduction, the quinoline-6-methanol. Introduction of chlorine at C-2 was followed by palladium-catalysed Suzuki coupling to install the 2-aryl substituent. A fluorescent model ‘drug’, 7-hydroxy-4-methylcoumarin was coupled to the 6-hydroxymethyl group, and its fragmentation upon reduction of the nitro group was investigated.     

Exploring the chemistry of penicillin as a beta-lactamase-dependent prodrug

The penam nucleus can be modified to behave as a beta-lactamase-dependent 'prodrug' by incorporation of a vinyl ester side chain at the 6-position. Enzyme-catalysed hydrolysis of the beta-lactam ring uncovers the thiazolidine-ring nitrogen as a nucleophile that drives a rapid intramolecular displacement on the side chain. Attachment of 7-hydroxy-4-methylcoumarin as the releasable group of this side chain generated a penicillin structure that can function as a fluorescence-based reporter substance/diagnostic for the presence of low levels of beta-lactamase enzyme in solution. Mechanistic details of the reaction pattern are documented and the scope and limitations of exploiting the structural modification are discussed.