cas 6066-49-5, 3-n-Butylphthalide | Articles data

Articles about 6066-49-5Total 56 be found

Article title
Article abstract
Author
Journal number and time
Download

Visible Light-Promoted Magnesium, Iron, and Nickel Catalysis Enabling C(sp3)-H Lactonization of 2-Alkylbenzoic Acids
A mild and practical C(sp3)-H lactonization protocol has been achieved by merging photocatalysis and magnesium (iron, nickel) catalysis. A diverse range of 2-alkylbenzoic acids with a variety of substitution patterns could be transformed into the corresponding phthalide products. Based on the mechanistic experimentation and reported prior studies, a possible mechanism for the benzylic oxidative lactonization reaction was proposed with the hypothetic photoactive ternary complex formed between the 2-alkylbenzoic acid substrate, magnesium ion, and bromate anion.
Li, Sasa,Su, Mincong,Sun, Jie,Hu, Kunjun,Jin, Jian
supporting information
p. 5842 - 5847
(2021/07/31)

Method for synthesizing butyl phthalide
The invention relates to a method for synthesizing butyl phthalide. The synthesis of butyl phthalide is realized through the reduction/lactonization cascade reaction of o-valeryl benzoate. Copper salt, silane and a phosphine ligand form a CuH reducing agent in an organic solvent, ketone carbonyl of o-valeryl benzoate is selectively reduced at the temperature of 0-40 DEG C, lactonization reaction is spontaneously performed under the reaction condition, and butyl phthalide is generated. The molar ratio of the copper salt to the phosphine ligand to silane to o-valeryl benzoate is (0.02-0.08): (0.02-0.08): (2-5): 1. According to the method, reaction under a high-temperature condition is not needed, and the yield is also obviously improved; no cadmium reagent or other reagents with high toxicity is used, so that the method is environment-friendly; the catalytic amount of CuH catalyst used in the method has the advantages of high yield and the like.
-
Paragraph 0027-0028

(2021/03/11)

Novel purification method of butylphthalide
The invention aims to provide a simple and easy-to-operate method for preparing high-purity butylphthalide. The method comprises the following steps: subjecting o-formylbenzoic acid to reacting with a Grignard reagent to prepare a reaction solution of butylphthalide, regulating the reaction solution to a certain pH value by using a specific acid at a certain temperature, extracting a product by using an organic solvent, and washing an organic phase by using an alkali so as to obtain high-purity butylphthalide. According to the method, silica gel column chromatography or a high-temperature and high-vacuum distillation method is not used; tedious multiple acid and alkali adjusting procedures for purifying butylphthalide is avoided; operation is simple and effective; and the method is suitable for industrial large-scale production.
-
Paragraph 0027-0038

(2021/06/26)

Butylphthalide ring-opening compound, pharmaceutical compound, and preparation methods, compositions and applications of butylphthalide ring-opening compound and pharmaceutical compound
The invention relates to the field of medicines, and in particular, relates to a butylphthalide ring-opening compound, a pharmaceutical compound and preparation methods and applications of the butylphthalide ring-opening compound and the pharmaceutical compound. The butylphthalide ring-opening compound has a structure represented by a formula (I), wherein R1 and R2 are the same or different and are independently selected from H, C1-C5 alkyl, C1-C5 hetero-alkyl and -SO2R6, and R6 is selected from H, C1-C5 alkyl, C1-C5 hetero-alkyl, an aromatic ring and a heterocyclic ring from a three-membered ring to an eight-membered ring; or R1 and R2 are connected to form a three-membered ring to an eight-membered ring; and X is C or N or is absent to form a five-membered ring or a six-membered ring. The compound can be fully absorbed by the human body by being combined with an active substance, and the biological activity of the active substance is further promoted. Particularly, after the compound is combined with edaravone, a compound with excellent biological activity can be obtained.
-
Paragraph 0122-0132

(2021/06/26)

α-Angelica lactone catalyzed oxidation of benzylic sp3C-H bonds of isochromans and phthalans
A metal-free organocatalytic system has been developed for highly efficient benzylic C-H oxygenations of cyclic ethers using oxygen as an oxidant. This oxidation reaction utilizes α-angelica lactone as a low cost/low molecular weight catalyst. The optimized reaction conditions allow the synthesis of valued isocoumarins and phthalides from readily available precursors in good yields. Mechanistic studies indicate that the reaction pathway likely involves a radical processviaa peroxide intermediate.
Das, Utpal,Deepake, Siddharth K.,Kumar, Pawan,Thatikonda, Thanusha
supporting information
p. 4046 - 4050
(2020/06/09)

Preparation method of high-purity butylphthalide
The invention relates to a preparation method of high-purity butylphthalide. The preparation method comprises the following steps: (1) preparing n-butyl magnesium bromide; (2) synthesizing 2-valerylbenzoic acid; (3) synthesizing butylphthalide; and (4) refining the butylphthalide. Due to the adoption of the technical scheme, the preparation method has the advantages that the n-butyl magnesium bromide is used as an initiator in the step (1), so that the initiation condition is mild, and the safety performance is improved; and the initiation temperature is 38-42 DEG C, and the reaction temperature is only 48-52 DEG C, so that the temperature is easy to implement in the mass production process; the 2-valerylbenzoic acid is used as the raw material, and carbonyl is reduced in a sodium borohydride aqueous solution mode, so that explosion easily caused by a solid feeding mode is avoided, and production safety is guaranteed; and the butylphthalide is refined in a reduced pressure distillationmode, so that the method is simple and easy to implement, and the purity of the obtained high-purity butylphthalide reaches 100%. The synthesis process of butylphthalide is stable, the preparation process is mild and controllable, and the method is suitable for batch production.
-
Paragraph 0035; 0037; 0047-0053

(2020/12/06)

Design, Synthesis and Antifungal Activities of 6-Substituted 3-Butylphthalide Derivatives against Phytopathogenic Fungi
In order to discover novel potential antifungal agents, a series of 6-substituted 3-butylphthalide derivatives were designed, synthesized and evaluated for their antifungal activities against nine phytopathogenic fungi. Preliminary bioassay tests showed that five 3-butylphthalide derivatives exhibited more potent antifungal activities than hymexazol at the concentration of 50 μg/mL. Especially, 3-butyl-6-nitro-2-benzofuran-1(3H)-one and 3-butyl-6-hydroxy-5-nitro-2-benzofuran-1(3H)-one had significant fungicidal activity against some phytopathogenic fungi. The EC50 of 3-butyl-6-nitro-2-benzofuran-1(3H)-one against FS, FO and FG were 6.6, 9.6 and 16.0 μg/mL, respectively. The EC50 of 3-butyl-6-hydroxy-5-nitro-2-benzofuran-1(3H)-one against BC, PO, VM, SS and AS were 6.3, 5.9, 10.0, 4.5 and 8.4 μg/mL, respectively. The preliminary structure–activity relationships (SARs) of all target compounds were also investigated.
Li, Yong,Luo, Zhongfu,Luo, Bilan,Lan, Qing,Fan, Judi,Xue, Wei,Miao, Jing,Li, Yi,Tang, Lei,Fan, Lingling
(2020/09/23)

Preparation method of butylphthalide
The invention discloses a of butylphthalide. The preparation method comprises the following steps: with phthalic anhydride as a starting material, carrying out condensation, hydrolysis, reduction andesterification reactions to obtain butylphthalide. According to the preparation method, reaction raw materials are easy to obtain, operation is simple, reaction conditions are relatively mild, requirements on equipment is low, crude drugs with a purity of more than 99.80% and meeting medicinal requirements can be obtained without rectification, and the preparation method is suitable for industrialproduction.
-
(2020/11/26)

Method for synthesizing 3 - n -butyl - l (3H)-isobenzofuranone (by machine translation)
The invention discloses a method for synthesizing 3 - n -butyl - l (3H)-isobenzofuranone, firstly mixing Grignard reagent with Lewis acid, adjusting pH to acidity by an acid reagent, extracting with an organic solvent, concentrating and removing an organic solvent to obtain 3 - n -butyl - l (3H)-isobenzofuranone. (by machine translation)
-
Paragraph 0060; 0061; 0063

(2020/07/24)

Study on the ArI-catalyzed intramolecularoxy-cyclization of 2-alkenylbenzamides to benzoiminolactones
A new intramolecularoxy-cyclization of 2-alkenylbenzamides catalyzed by ArI has been developed. This protocol is highlighted by its metal-free catalytic system and extremely short reaction time, providing efficient and straightforward access to various benzoiminolactones in good to excellent yields. Interestingly, a regioselective transformation occurred when using two different reaction systems. Mechanistic studies suggested thatmCPBA acts as both oxidant and ligand at the IIIIcenter, and the Lewis acid BF3accelerated ligand exchange and reductive elimination in the catalytic process.
Deng, Xiaojun,He, Wei,Huang, Xie,Ji, Nan,Liu, Huixia
p. 3654 - 3658
(2020/06/03)

Purification method of 3-n-butyl-1-(3H)-isobenzofuranone
The invention discloses a purification method of 3-n-butyl-1-(3H)-isobenzofuranone, which mainly comprises the following steps: mixing a 3-n-butyl-1-(3H)-isobenzofuranone crude product with water, andregulating the pH value to be alkaline by using an alkaline reagent; extracting with an organic solvent, collecting an organic phase, and removing the solvent. According to the purification method disclosed by the invention, a high-purity product can be obtained without high-temperature and high-vacuum distillation, so that the operation is simple, the raw materials are easy to obtain, the yieldis high, the cost is low, and the industrialization prospect is better.
-
Paragraph 0037-0046

(2020/07/24)

Method for preparing high-purity butyphthalide
The invention relates to a method for preparing high-purity butyphthalide. The method comprises the following steps: dissolving phthalaldehydic acid in an organic solvent, reacting with n-butyllithiumin a micro-channel reactor to generate a butyphthalide crude product, and carrying out aftertreatment to obtain the high-purity butyphthalide. The method overcomes the disadvantages that the yield for preparing the butyphthalide is low, the reaction temperature is high and the product color grade is high in existing phthalic acid method and valeric anhydride reaction; and moreover, the technicalproblems that magnesium ions are difficult to remove through aftertreatment and the high-purity butyphthalide is difficult for industrial production when the butyphthalide is prepared in the reactionof o-formoxyl benzoic acid and butyl magnesium bromide. The method is high in yield, the raw materials are easily obtained, and the prepared butyphthalide is high in purity and is applicable for industrial production.
-
Paragraph 0056; 0058-0059; 0052; 0054-0056; 0060; 0062-0063

(2019/07/29)

Rhenium-Catalyzed Phthalide Synthesis from Benzamides and Aldehydes via C-H Bond Activation
The [4 + 1] annulation of benzamides and aldehydes for phthalide synthesis was achieved via rhenium-catalyzed C-H activation, which demonstrates an unprecedented reaction pattern distinct from those of other transition-metal catalyses. The reaction also features readily available starting materials, a wide scope for both electro-rich and electro-deficient substrates, and the elimination of homoannulation byproducts.
Jia, Bing,Yang, Yunhui,Jin, Xiqing,Mao, Guoliang,Wang, Congyang
p. 6259 - 6263
(2019/09/06)

Palladium-Catalyzed Direct Oxidative Coupling of Iodoarenes with Primary Alcohols Leading to Ketones: Application to the Synthesis of Benzofuranones and Indenones
In the present study, a palladium-catalyzed direct oxidative acylation through cross-dehydrogenative coupling has been investigated, utilizing readily available primary alcohols as acylating sources. Overall, this oxidative coupling proceeds via three distinct transformations such as oxidation, radical formation, and cross-coupling in one catalytic process. This protocol does not involve the assistance of a directing group or activation of the carbonyl group by any other means. Furthermore, this reaction made use of no toxic CO gas as carbonylating agent; instead, feedstock primary alcohols have been utilized as acylation source. Notably, the synthesis of benzofuranones and indenones is enabled. This strategy was also applied to the synthesis of n-butylphthalide, fenofibrate, pitofenone, and neo-lignan.
Suchand, Basuli,Sreenivasulu, Chinnabattigalla,Satyanarayana, Gedu
p. 4832 - 4843
(2019/07/31)

Synthesis of 1,2-phenylenedimethanols by base-promoted reduction of isobenzofuran-1(3H)-ones with silane
An efficient method for preparation of substituted 1,2-phenylenedimethanols and aliphatic 1,4-diols that are valuable intermediates in organic synthesis, has been developed by the base-promoted reduction of isobenzofuran-1(3H)-ones and γ-lactones with silane under mild conditions. Compared with traditional procedures using stoichiometric amounts of metal hydrides and alkyl reductants, the present method avoids the use of sensitive reagents and is operationally simple and a broad variety of functional groups are tolerated.
Liu, Bin,Zhou, Xigeng
supporting information
p. 725 - 728
(2018/12/11)

Preparation method of butylphthalide and pharmaceutical intermediate thereof
The present invention provides a new pharmaceutical intermediate and a method for preparing butylphthalide by using the new pharmaceutical intermediate. According to the method, o-phthalic acid monoester as a raw material and valerate are subjected to ester condensation, o-pentanoylbenzoic acid is prepared through hydrolysis and decarboxylation, and reducing with sodium borohydride and ring closure are performed to obtain the product. According to the present invention, the method has characteristics of inexpensive and easily-available raw material, mild reaction condition, no high-temperaturereaction, no Grignard reaction, production energy consumption reducing, production cost reducing and operation safety improving.
-
Paragraph 0035

(2018/11/03)

A controllable bulk drug product and its preparation method
The present invention provides a butyl phthalide raw material drug product with the butyl phthalide content not less than 99.0%; the raw material drug is stable in quality, and can ensure the clinical curative effect and drug safety of a butyl phthalide preparation.
-
Paragraph 0086; 0091; 0092

(2018/12/13)

Simple method for preparing high-purify butyphthalide
The invention provides a simple method for preparing high-purity butyphthalide. The simple method includes subjecting carboxybenzaldehyde, as a starting material, and normal-butyl halogenated (brominated or chlorinated) Grignard reagent or n-butyllithium to reaction in organic solution to obtain a reaction solution; after the reaction, adding water solution into the reaction solution dropwisely, extracting or removing organic solvents by reduction vaporization to obtain 2-(1-hydroxy-amyl) benzoate solution, subjecting 2-(1-hydroxy-amyl) benzoate solution to extraction by organic solvents whileregulating the pH to obtain 2-(1-hydroxy-amyl) benzoic acid, dissolving 2-(1-hydroxy-amyl) benzoic acid in organic solvents, performing cyclization reaction, sequentially washing with saturated sodium bicarbonate solution and sodium chloride solution, drying, and then performing reduced-pressure distillation to obtain high-purity butyphthalide. The synthesis method is simple and convenient to operate as column chromatography, reduced-pressure rectification or frequent acidifying or alkalizing or frequent to purify samples by ring-opening or ring-closing reactions are omitted, and accordinglyis adaptable to industrialized production. By the simple method, colorless products with purity being or higher than 99% can be obtained without decoloration or purification.
-
Paragraph 0015; 0016; 0017; 0018; 0019; 0020

(2019/01/14)

Controlled photo-flow oxidative reaction (UV-FOR) platform for ultra-fast phthalide and API synthesis
An integrated photo-flow oxidative reaction (UV-FOR) platform approach is presented for the synthesis of phthalides. The current protocol is catalyst-free, and uses economical and abundant hydro-carbons and hydrocarbon derivatives such as benzoic acid, benzene, and xylene, as starting materials. The reaction is performed using oxygen as a green oxidant in a time- and labour-efficient manner. This integrated approach has been shown to be successful in making a UV-FOR platform suitable for the on-demand synthesis of phthalides and their further syntheses to 2-arylmethylbenzoic acids and arylogous Michael addition products under relatively mild conditions. The current protocol was further extended to the gram scale synthesis of an ischemic stroke-relevant active pharmaceutical ingredient (API), 3-N-butylphthalide (NBP), in a continuous flow process.
Aand, Dnyaneshwar,Karekar, Sanjeev,Mahajan, Bhushan,Pawar, Amit B.,Singh, Ajay K.
supporting information
p. 4584 - 4590
(2018/10/23)

Process for preparing butyphthalide
The invention relates to a process for preparing butyphthalide. A one-pot method is adopted, the process is easy to operate, and industrial production has remarkable advantages. The process comprisesthe following steps: making 1,2-dibromo-benzene serving as an initial material react with carbon dioxide ice under the action of n-BuLi to generate an intermediate; directly adding n-BuLi into an intermediate solution without quenching the reaction; making the mixture react with n-valeraldehyde; treating a reaction liquid with HCl; and performing column chromatography and purification to obtain the butylphthalide.
-
Paragraph 0015; 0016; 0017

(2018/07/10)

Ir-SpinPHOX Catalyzed Enantioselective Hydrogenation of 3-Ylidenephthalides
The first asymmetric hydrogenation of 3-ylidenephthalides has been developed using the IrI complex of a spiro[4,4]-1,6-nonadiene-based phosphine-oxazoline ligand (SpinPHOX) as the catalyst, affording a wide variety of chiral 3-substituted phthalides in excellent enantiomeric excesses (up to 98 % ee). The utility of the protocol has been demonstrated in the asymmetric synthesis of chiral drugs NBP and BZP precursor, as well as the natural products chuangxinol and typhaphthalide.
Ge, Yao,Han, Zhaobin,Wang, Zheng,Feng, Chen-Guo,Zhao, Qian,Lin, Guo-Qiang,Ding, Kuiling
supporting information
p. 13140 - 13144
(2018/09/21)

Preparation method of chiral phthalide derivative
The invention discloses a preparation method of a chiral phthalide derivative shown as Formula II. The preparation method of the chiral phthalide derivative comprises a step of causing hydrogenation reduction reaction as shown below between the compound shown as Formula I and hydrogen in an organic solvent under the action of an iridium complex so as to obtain the chiral phthalide derivative. Thepreparation method of the chiral phthalide derivative disclosed by the invention is free of involvement of alkali or additives, mild in reaction conditions, easy to operate, wide in reaction substrateapplication range, free of by-product formation, good in stereoselectivity, high in yield, high in synthesis efficiency, economical and environmentally friendly; and thus, the preparation method of the chiral phthalide derivative has good application prospects.
-
Paragraph 0141-0146

(2019/01/06)

Incorporation of carbon dioxide into phthalides: Via ligand-free copper-catalyzed direct carboxylation of benzoxasiloles
The direct carboxylation of benzoxasiloles with carbon dioxide proceeded smoothly under mild conditions using copper iodide as a catalyst to afford phthalides after an acid work-up. Broad substrate scope and application of this methodology for the synthesis of natural products highlight the synthetic utility of this protocol.
Nguyen, Thanh V. Q.,Rodríguez-Santamaría, José A.,Yoo, Woo-Jin,Kobayashi, Shu
supporting information
p. 2501 - 2505
(2017/07/17)

DL-3-n-butylphthalide-Edaravone hybrids as novel dual inhibitors of amyloid-β aggregation and monoamine oxidases with high antioxidant potency for Alzheimer's therapy
Considering the complex etiology of Alzheimer's disease (AD), multifunctional agents may be beneficial for the treatment of this disease. A series of DL-3-n-butylphthalide-Edaravone hybrids were designed, synthesized and evaluated as novel dual inhibitors of amyloid-β aggregation and monoamine oxidases. Among them, compounds 9a–d exhibited good inhibition of self-induced Aβ1-42aggregation with inhibition ratio 57.7–71.5%. For MAO, these new hybrids exhibited good balance of inhibition for MAO-A and MAO-B. In addition, all target compounds retained the antioxidant activity of edaravone, showed equal or better antioxidant activity than edaravone. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that compounds 9a–d would be able to cross the blood-brain barrier and reach their biological targets in the central nervous system. The promising results in all assays demonstrated that the strategy behind the designing of compounds was rational and favourable. Taken together, these preliminary findings suggested that the compounds with the strongest bioactivity deserves further investigated for pharmacological development in AD therapy.
Qiang, Xiaoming,Li, Yan,Yang, Xia,Luo, Li,Xu, Rui,Zheng, Yunxiaozhu,Cao, Zhongcheng,Tan, Zhenghuai,Deng, Yong
p. 718 - 722
(2017/02/10)

Ruthenium-Catalyzed Enantioselective Hydrogenation/Lactonization of 2-Acylarylcarboxylates: Direct Access to Chiral 3-Substituted Phthalides
Highly enantioselective tandem hydrogenation/lactonization of various 2-acylarylcarboxylates including 2-aroylarylcarboxylates were realized by using [RuCl(benzene)(S)-SunPhos]Cl as the catalyst under mild reaction conditions. Excellent enantioselectivities (up to 99.6 % ee) and activities (S/C=1000) were obtained. This convenient and practical method enables a direct access to a series of highly optically pure 3-substituted phthalides that are very important molecules as valuable pharmacological compounds and diversified synthons for medicinal chemistry. Moreover, a gram-scale reaction was performed to further demonstrate the practicality of this approach.
Lu, Bin,Zhao, Mengmeng,Ding, Guangni,Xie, Xiaomin,Jiang, Lili,Ratovelomanana-Vidal, Virginie,Zhang, Zhaoguo
p. 3989 - 3996
(2017/09/13)

Butyphthalide preparation method
The invention provides a butyphthalide preparation method which comprises the following steps: S1) utilizing raney nickel as a catalyst, performing hydrogenation reaction on butylidene phthalide in an alcohol solvent and reducing pressure to remove the solvent to obtain a first intermediate; S2) mixing the first intermediate, sodium hydroxide and water to react, then utilizing dichloromethane to wash a reaction system, then adding the alcohol solvent and performing acid adjusting reaction to obtain a second intermediate; S3) performing cyclization reaction on the second intermediate in an acid organic solvent to obtain butyphthalide. Compared with the prior art, the butyphthalide preparation method disclosed by the invention utilizes the alcohol solvent and the dichloromethane as reaction or extraction solvents; the alcohol solvent and the dichloromethane both can be effectively recycled and is low in cost, so that production cost is greatly reduced; through hydrolyzing purification and acid adjusting filtration purification, high-purity butyphthalide meeting a preparation requirement can be obtained in higher yield; the steps of reducing pressure and rectifying are avoided, and operation is simple.
-
(2017/10/13)

Preparation method for high-purity butyphthalide
The invention provides a preparation method for high-purity butyphthalide. The method comprises the following steps: S1) taking Raney nickel as a catalyst, performing hydrogenation reaction on butylidene phthalide in an alcohol solvent, removing the solvent at reduced pressure, thereby obtaining a first intermediate; S2) mixing the first intermediate with potassium hydroxide, tetrahydrofuran and water and reacting, and cooling and crystallizing after ending the reaction, thereby obtaining a second intermediate; and S3) performing cyclization reaction on the second intermediate in an acidic organic solvent, thereby obtaining butyphthalide. Compared with the prior art, the preparation method has the advantages that the alcohol solvent and tetrahydrofuran are taken as reaction solvents, can be effectively recycled and are low in cost, so that the production cost is greatly lowered; and meanwhile, the requirement for a refining tower of the production equipment is reduced through the hydrolysis refining, no repeated refining is required, and the energy is saved.
-
(2017/10/23)

Ligustrazine-butyphthalide combination compound, preparation method of ligustrazine-butyphthalide combination compound, and application of ligustrazine-butyphthalide combination compound to pharmaceuticals
The invention discloses a ligustrazine-butyphthalide combination compound, a preparation method of the ligustrazine-butyphthalide combination compound and an application of the ligustrazine-butyphthalide combination compound to pharmaceuticals. The ligustrazine-butyphthalide combination compound has the following structural formula I as in the description. The phthalic anhydride and the ligustrazine are taken as starting materials, bromization, nucleophilic addition, catalytic dehydration, ester hydrolysis, reduction and esterification reactions are conduced to prepare the ligustrazine-butyphthalide combination compound; a pharmaceutical composition takes the ligustrazine-butyphthalide combination compound as an active pharmaceutical ingredient and is a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, intermedium or a composition. The prepared ligustrazine-butyphthalide combination compound has an excellent effect of inhibiting in-vitro platelet aggregation (ADP) induced platelet aggregation, has a better in-vivo pharmacokinetics properties, and can be used for preventing and treating cardiovascular and cerebrovascular diseases, vascular senile dementia and the complications.
-
(2017/08/30)

High-content butylphenyl phthaleine composition and preparation method thereof
The invention provides a high-content butylphenyl phthaleine composition. The butylphenyl phthaleine pharmaceutical composition comprises the following components: active component butylphenyl phthaleine, wherein the butylphenyl phthaleine content is no less than 99.5%; impurity with amount of no greater than 0.5% by metering weight percentage sum of butylphenyl phthaleine, wherein after placing for 24 months under normal condition, the butylphenyl phthaleine content is no less than 99.0%; and the impurity with amount of no greater than 1.0% by metering the weight percentage sum of butylphenyl phthaleine.
-
Paragraph 0054

(2017/06/07)

Butylphthalide synthesis method and purification technology
The invention relates to a butylphthalide synthesis method. The method comprises the steps that methyl 2-formyl benzoic acid is adopted as a starting material, THF is adopted as a solvent to react with an n-butyl magnesium chloride Grignard reagent, and acid regulation is performed to prepare a butylphthalide product. The invention further relates to a technology for preparing high-purity butylphthalide. The obtained crude butylphthalide product is subjected to hydrolysis treatment by an alkaline substance, acid regulation is performed to separate out solids, and filtering is performed to obtain a butylphthalide midbody; the acid regulation and alkali regulation processes are executed repeatedly, and finally ring closure and decompression desolvation are performed to obtain high-purity butylphthalide. According to the synthesis method, low-flash diethyl ether is prevented from being adopted as a solvent, the purification technology is easy to implement, the reagent can be purchased in bulk easily, column chromatography product purification and reduced pressure distillation under high temperature and high vacuum degree are not needed, and industrial enlarged production is easy.
-
Paragraph 0065; 0066; 0072

(2017/05/26)

A method for preparing high-purity Butylphthalide (by machine translation)
The present invention provides a method for preparing high-purity phthalein, including A. The meso -3 the phthalide-butyl [...] crude product into the reaction bottle, the vacuum degree of the reduced pressure to system 1 the [...] 2mbar; heating, collect the 130 [...] 140 °C fraction to obtain racemic -3 the [...] butyl [...] ; B. The meso -3 the n-butyl [...][...] and methanol, are added to a reaction flask, stirring is dissolved, add the inorganic alkali methanol solution, heating to reflux the reaction, filtered, concentrated to remove methanol, by adding dichloromethane, agitating precipitated solid, filtering, drying to obtain the 1 [...] pentylimidazolium -2 the benzoate [...] ; C. The the 1 [...] pentylimidazolium -2 the salt benzoate [...] stirring to dissolve into the water, then adding a solution of hydrochloric acid in the reaction bottle, in the 35 [...] 45 °C stirring reaction of the temperature, of layering, oil phase are sequentially with sodium bicarbonate solution, washing, drying, filtering to obtain racemic -3 the phthalide-butyl [...] pure product. (by machine translation)
-
Paragraph 0054; 0055

(2016/12/26)

Palladium-Catalyzed Environmentally Benign Acylation
Recent trends in research have gained an orientation toward developing efficient strategies using innocuous reagents. The earlier reported transition-metal-catalyzed carbonylations involved either toxic carbon monoxide (CO) gas as carbonylating agent or functional-group-assisted ortho sp2 C-H activation (i.e., ortho acylation) or carbonylation by activation of the carbonyl group (i.e., via the formation of enamines). Contradicting these methods, here we describe an environmentally benign process, [Pd]-catalyzed direct carbonylation starting from simple and commercially available iodo arenes and aldehydes, for the synthesis of a wide variety of ketones. Moreover, this method comprises direct coupling of iodoarenes with aldehydes without activation of the carbonyl and also without directing group assistance. Significantly, the strategy was successfully applied to the synthesis n-butylphthalide and pitofenone.
Suchand, Basuli,Satyanarayana, Gedu
p. 6409 - 6423
(2016/08/16)

NOVEL SINGLE STEP ESTERIFICATION PROCESS OF ALDEHYDES USING A HETEROGENEOUS CATALYST
The present invention relates to a novel simple, efficient and single-step process for esterification of aldehydes using a heterogeneous catalyst with high yields. More particularly, the present invention relates to a novel simple, efficient and single-step process for esterification of aldehydes using Titanium superoxide with greater than 80% yields.
-
(2016/06/20)

Method used for preparing n-butylphathlide via one pot method
The invention belongs to the technical field of chemical synthesis, and more specifically relates to a method used for preparing n-butylphathlide via one pot method. The method comprises following steps: phthalic anhydride and valeric anhydride are subjected to a first step reaction under catalytic action of anhydrous sodium acetate, and generated n-pentanoic acid is collected via reduced pressure distillation; a sodium hydroxide solution of sodium borohydride is added into a reaction liquid for a second step of reaction; dichloromethane is used for extracting impurities; pH value is adjusted to be smaller than 7 with an acid for a third step of reaction, dichloromethane is used for extracting, and n-butylphathlide is obtained via concentration. The method is high in yield, low in cost, is safe, and is friendly to the environment.
-
Paragraph 0023

(2017/01/19)

Domino [Pd]-Catalysis: One-Pot Synthesis of Isobenzofuran-1(3H)-ones
An efficient domino [Pd]-catalysis for the synthesis of isobenzofuran-1(3H)-ones is presented. The strategy shows broad substrate scope and is amenable to o-bromobenzyl tertiary/secondary/primary alcohols. Significantly, the method was applied to the synthesis of antiplatelet drug n-butyl phthalide and cytotoxic agonist 3a-[4′-methoxylbenzyl]-5,7-dimethoxyphthalide.
Mahendar, Lodi,Satyanarayana, Gedu
p. 7685 - 7691
(2016/09/09)

Preparation method of high-purity n-butylphthalide
The invention belongs to the technical field of medicine, and relates to a method for easily and efficiently synthesizing n-butylphthalide. The method particularly comprises the following steps that in the presence of a copper iodide catalyst, o-cyanobenzaldehyde is reacted with a Grignard reagent of n-butyl bromide in solvent; hydrochloric acid is added for a reaction after the reaction in the first step is completed, standing layering is conducted, and an organic phase is obtained; the organic phase is washed through an aqueous hydrochloric acid solution, a sodium hydroxide aqueous solution is added, reflux is conducted through heating, standing layering is conducted after reflux is completed, and an aqueous phase is obtained; pH of the aqueous phase is adjusted to 3-4, a reaction is conducted through heating, solvent extraction is conducted after the reaction is completed, concentration and vacuum distillation are conducted on an obtained oil phase, and a finished product is obtained. According to the method for easily and efficiently synthesizing the n-butylphthalide, the raw materials are easy to obtain, the yield is high, the cost is low, industrialization is easy, the n-butylphthalide with the content of any individual impurity smaller than 0.1 percent can be obtained, and the purity is larger than 99.7 percent.
-
Paragraph 0018

(2016/10/08)

A PROCESS FOR THE SYNTHESIS OF CARBOXYLIC ACID DERIVATIVES
The present invention discloses one-pot synthesis of various carboxylic acid derivatives using copper catalyst and sodium cyanide as the cyanide source for bringing in carbonylative coupling in a single step.
-
Page/Page column 8-9; 15

(2015/05/19)

Titanium superoxide-a stable recyclable heterogeneous catalyst for oxidative esterification of aldehydes with alkylarenes or alcohols using TBHP as an oxidant
Titanium superoxide efficiently catalysed the oxidative esterification of aldehydes with alkylarenes or alcohols, under truly heterogeneous conditions, to afford the corresponding benzyl and alkyl esters in excellent yields. Mechanistic studies have established that this "one pot" direct oxidative esterification process proceeds through a radical pathway, proven by a FTIR spectral study of a titanium superoxide-aldehyde complex as well as spin trapping experiments with TEMPO. The intramolecular version of this protocol has been successfully demonstrated in the concise synthesis of 3-butylphthalide, an anti-convulsant drug.
Dey, Soumen,Gadakh, Sunita K.,Sudalai
p. 10631 - 10640
(2015/11/17)

Novel hybrids of 3-n-butylphthalide and edaravone: Design, synthesis and evaluations as potential anti-ischemic stroke agents
Abstract Fourteen hybrids (10a-g, 11a-g) of 3-n-butylphthalide (NBP) and edaravone (Eda) analogues have been designed and synthesized as potential anti-ischemic stroke agents. In vitro biological studies showed that compounds 10d and 10g exhibited more potent anti-platelet aggregation than ticlopidine (Ticlid), aspirin (ASP) and NBP. Compound 10g more significantly prevented H2O2-mediated neuronal cell (PC12) death than NBP, Eda or NBP together with Eda. Meanwhile, 10g also possessed potent radical scavenging effects on hydroxyl radical (·OH) and superoxide anion radical (·O2-). Our findings may provide new insights into the development of these hybrids, like 10g, for the intervention of ischemic stroke.
Sheng, Xiao,Hua, Kai,Yang, Chunyu,Wang, Xiaoli,Ji, Hui,Xu, Jinyi,Huang, Zhangjian,Zhang, Yihua
p. 3535 - 3540
(2015/08/06)

Cu-MEDIATED ANNULATION FOR THE EFFECTIVE SYNTHESIS OF 3-SUBSTITUTED PHTHALIDES
The present invention disclosed herein is a novel commercially feasible, one pot synthesis of library of 3-substituted phthalides of formula I via CuCN mediated oxidative cyclization in high yield. Formula I
-
Page/Page column 0118; 0119

(2015/02/25)

Copper(I) bromide-catalyzed carbonylative coupling of aryl halides with phenols, alcohols and amines using sodium cyanide as C1 source: A synthesis of carboxylic acid derivatives
A new carbon monoxide-free synthesis of carboxylate derivatives via carbonylative coupling of aryl bromides with phenols, alcohols, amines and acids in the presence of copper(I) bromide as catalyst and sodium cyanide in a stoichiometric amount has been developed. Its intramolecular version provides for the preparation of lactones (e.g., isochroman-1-ones and isobenzfuranones), imides, anhydrides and lactams in excellent yields (73-96%).
Prasad, Pragati K,Sudalai, Arumugam
supporting information
p. 2231 - 2238
(2014/07/21)

Transition-metal-free synthesis of (Z)-3-ylidenephthalides from 2-acyl-benzoic acids
We report a highly efficient method for the synthesis of (Z)-3-ylidenephthalides via intramolecular cyclization of readily available 2-acyl-benzoic acids mediated by TSTU at room temperature. Using this method, diversely substituted (Z)-3-ylidenephthalides have been generated in good to excellent yields. The application of the method is highlighted by gram-scale preparation of the antiplatelet drug n-butylphthalide.
He, Xinhua,Xue, Fengtian
supporting information
p. 1956 - 1958
(2014/03/21)

A concise synthesis of 3,4-fused spiro[isobenzofuran-3-ones], spiro[furo[3,4-b]pyridin-5(7H)-ones], 3-aryl-, and alkylphthalides
A synthetically useful protocol has been developed for the preparation of highly functionalized 3,4-fused spiro[isobenzofuran-3-ones], spiro[furo[3,4-b]pyridin-5(7H)-ones], 3-aryl-, and alkylphthalides. Reaction of 2-iodobenzoate esters and 2-iodopyridine carboxylate esters with i-PrMgCl·LiCl in the presence of cyclic ketones under standard Barbier reaction conditions affords 3,4-fused spiro[isobenzofuran-3-ones] and spiro[furo[3,4-b]pyridin-5(7H)-ones] in good to excellent yields. Step-wise addition of i-PrMgCl·LiCl to 2-iodobenzoate esters followed by trapping with various aldehydes yields 3-aryl and 3-alkylphthalides; whereas, under similar conditions access to 3-aryl and 3-alylazaphthalides is also possible. Extension of this methodology toward the preparation of 3-n-butylphthalide and chrycolide, a natural product isolated from the leaves and stems of Chrysanthemum coronarium, is also described.
Kuethe, Jeffrey T.,Maloney, Kevin M.
p. 5248 - 5258
(2013/06/27)

Cu-MEDIATED ANNULATION FOR THE EFFECTIVE SYNTHESIS OF 3-SUBSTITUTED PHTHALIDES
The present invention disclosed herein is a novel commercially feasible, one pot synthesis of library of 3-substituted phthalides of formula I via CuCN mediated oxidative cyclization in high yield. Formula I
-
Page/Page column 21

(2013/07/19)

Asymmetric synthesis and sensory evaluation of sedanenolide
The synthesis and sensory evaluation of enantiomeric sets of sedanenolide (1) and 3-butylphthalide (3) are described. The asymmetric synthesis was achieved via the intramolecular Diels-Alder reaction of chiral propargylester (5) which was prepared from optically active propargyl alcohol (4) and 2,4-pentadienoic acid. The sensory evaluation of these enantiomers revealed that there were distinct differences between their aroma character and odor threshold.
Oguro, Daichi,Watanabe, Hidenori
p. 1502 - 1505
(2011/11/04)

Design, synthesis and evaluation of nitric oxide releasing derivatives of 3-n-butylphthalide as antiplatelet and antithrombotic agents
Novel nitric oxide (NO) releasing derivatives (7a-7l) of 3-n-butylphthalide (NBP) were designed and synthesized. Compound 7e inhibited the adenosine diphosphate (ADP), thrombin (TH) and arachidonic acid (AA)-induced in vitro platelet aggregation, superior to NBP and aspirin, released moderate levels of NO, and improved aqueous solubility relative to NBP. Furthermore, 7e exhibited greater antithrombotic activity than NBP and aspirin in rats, and protected against collagen and adrenaline-induced thrombosis in mice. Therefore, NO-releasing NBP derivatives possessed potent antiplatelet aggregation and antithrombotic activity. Our findings may aid in the design of new therapeutic agents for the treatment of thrombosis-related ischemic stroke.
Wang, Xuliang,Li, Yang,Zhao, Qian,Min, Zhenli,Zhang, Chao,Lai, Yisheng,Ji, Hui,Peng, Sixun,Zhang, Yihua
experimental part
p. 5670 - 5681
(2011/09/15)

Synthesis and evaluation of nitric oxide-releasing derivatives of 3-n-butylphthalide as anti-platelet agents
Most ischemic stroke results from brain blood vessel blockage by platelet-mediated thrombus, and anti-platelet therapy has been demonstrated clinical benefits in the treatment of this disease. In the present work, novel nitric oxide (NO)-releasing derivatives of an anti-ischemic stroke drug 3-n-butylphthalide (NBP) were synthesized. Compounds 7a and 7c exhibited more potent anti-platelet activity than NBP and aspirin, and released a moderate amount of NO, which is beneficial in improving cardiovascular and cerebral circulation. These findings provide an alternative approach to the development of drugs more potent than NBP for the intervention of ischemic stroke.
Li, Yang,Wang, Xuliang,Fu, Rong,Yu, Wenying,Wang, Xiaoli,Lai, Yisheng,Peng, Sixun,Zhang, Yihua
scheme or table
p. 4210 - 4214
(2011/08/06)

Butylphthalide Self-Emulsifying Drug Delivery System, Its Preparation Method and Application
The present invention relates to a novel drug delivery and release system, i.e. Self-emulsifying Drug Delivery System (SEDDS), of butylphthalide, to a preparation process thereof, and to a use thereof in a pharmaceutical formulation. The drug delivery system comprises as essential ingredients 1% to 65% of butylphthalide and 10% to 65% of a emulsifying agent, together with various excipients as required depending on the desired dosage forms. The present invention significantly increases the contact area between butylphthalide and the mucous membrane of the gastrointestinal tract, and therefore improves the absorptivity of the drug.
-
(2009/01/24)

Synthesis, resolution, and antiplatelet activity of 3-substituted 1(3H)-isobenzofuranone
A series of 3-substituted-1(3H)-isobenzofuranone 6a-g and 7a-g were synthesized from phthalic anhydride. The compound 6a-g was resolved. The antiplatelet activities of these compounds were evaluated using in vitro experiment of platelet aggregation. The levels of antiplatelet activity were displayed as following sequence: l-isomer > dl-isomer > d-isomer, respectively. The alkylphthalide is more active than the corresponding alkenephthalide. All these compounds were less active than n-butylphthalide (NBP, 6c) and Aspirin (Asp).
Yang, Hua,Hu, Gao-Yun,Chen, Jun,Wang, Yi,Wang, Zhong-Hua
p. 5210 - 5213
(2008/02/11)

Solid-phase synthesis of isoindolinones and naturally-occurring benzobutyrolactones (phthalides) using a cyclative-cleavage approach
Starting from Merrifield resin, 2-formylbenzoic acids were immobilized on solid supports. Reactions between immobilized 2-formylbenzoic acids and different organometallic reagents (Grignard reagents, zinc reagents, allyl silanes via Sakurai type reactions) furnished secondary alcohols which cyclized depending on the metal counter ion and reaction conditions, forming benzoannelated lactones. Asymmetric synthesis was possible on the resin using chiral [2.2]paracyclophane ligands. While the reaction of immobilized ortho-carboxy benzaldehydes with primary amines at elevated temperatures yielded 3-hydroxyisoindolinones, a reaction at ambient temperature allowed imine formation, which underwent 1,2-addition-cleavage reaction with various nucleophiles, yielding isoindolinones with three points of diversity.
Knepper, Kerstin,Ziegert, Robert E.,Br?se, Stefan
p. 8591 - 8603
(2007/10/03)