- Anthelmintic activity of albendazole against liver flukes, tapeworms, lung and gastrointestinal roundworms
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A new derivative, albendazole, of the benzimidazole group of anthelmintics which is active against nematode, cestode and trematode species, was found.
- Theodorides,Gyurik,Kingsbury,Parish
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Read Online
- Scalable electrochemical reduction of sulfoxides to sulfides
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A scalable reduction of sulfoxides to sulfides in a sustainable way remains an unmet challenge. This report discloses an electrochemical reduction of sulfoxides on a large scale (>10 g) under mild reaction conditions. Sulfoxides are activated using a substoichiometric amount of the Lewis acid AlCl3, which could be regeneratedviaa combination of inexpensive aluminum anode with chloride anion. This deoxygenation process features a broad substrate scope, including acid-labile substrates and drug molecules.
- Kong, Zhenshuo,Pan, Chao,Li, Ming,Wen, Lirong,Guo, Weisi
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supporting information
p. 2773 - 2777
(2021/04/21)
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- Preparation method of albendazole
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The invention discloses a preparation method of albendazole, which comprises the following steps of: dissolving 4-propylthio-o-phenylenediamine in methanol, cooling, keeping the temperature at 0-5 DEGC, slowly dropwise adding cyanogen chloride for reaction under the condition of uniform stirring, and regulating and keeping the pH value at 4-5 in the process; heating to 35-45 DEG C after dropwiseadding is finished, carrying out heat preservation for 1-2 hours, then carrying out atmospheric distillation to recover methanol to obtain a solid-liquid mixed aqueous solution, and carrying out cooling, filtering and drying to obtain 6-propylthio-2-amino-1-hydrogen-benzo [d] imidazole; adding the obtained product into methanol, stirring, cooling, maintaining the temperature at 5-10 DEG C, slowlydropwise adding methyl chloroformate, and adjusting and maintaining the pH value at 6-7; after dropwise adding is finished, heating to 35-45 DEG C, keeping the temperature for 1-2 hours, distilling atnormal pressure to recover methanol, cooling to 15-20 DEG C, and performing filtering and drying to obtain an albendazole product. The method has the advantages of mild process conditions, low cost of used raw materials, water saving, strong reaction activity, good selectivity, high product yield and good product quality.
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- Electrophilic Chlorine from Chlorosulfonium Salts: A Highly Chemoselective Reduction of Sulfoxides
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Herein, we describe a selective late-stage deoxygenation of sulfoxides based on a novel application of chlorosulfonium salts and demonstrate a new process using these species generated in situ from sulfoxides as the source of electrophilic chlorine. The use of highly nucleophilic 1,3,5-trimethoxybenzene (TMB) as the reducing agent is described for the first time and applied in the deoxygenation of simple and functionalized sulfoxides. The method is easy to handle, economic, suitable for gram-scale operations, and readily applied for poly-functionalized molecules, as demonstrated with more than 45 examples, including commercial medicines and analogues. We also report the results of competition experiments that define the more reactive sulfoxide and we present a mechanistic proposal based on substrate and product observations.
- Acosta-Guzmán, Paola,Mahecha-Mahecha, Camilo,Gamba-Sánchez, Diego
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supporting information
p. 10348 - 10354
(2020/07/13)
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- Albendazole synthesis method
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The invention discloses an albendazole synthesis method. The albendazole synthesis method includes reacting ammonium thiocyanate with chlorine gas in a lower alcohol solvent to obtain chlorothiocyanate, reacting ortho-nitroaniline with the chlorothiocyanate in the lower alcohol solvent to obtain 4-thiocyano-2-nitroaniline, reacting the 4-thiocyano-2-nitroaniline with a sodium hydroxide solution toobtain 4-sodium sulfonate-2-nitroaniline, performing hydrochloric acid acidification to obtain 4-mercapto-2-nitroaniline, subjecting the 4-mercapto-2-nitroaniline and propylene to Markovnikov addition reaction to obtain 4-propylthio-2-nitroaniline, and reacting 4-propylthio-o-phenylenediamine with methylcyanocarbamate to obtain albendazole. The albendazole synthesis method has the advantages thata novel synthetic route is applied to prepare the albendazole, the defects of high impurity quantity and low yield in the current production process are overcome, the chlorothiocyanate is prepared toserve as an intermediate and then reacts with the ortho-nitroaniline, and impurities can be avoided effectively; the propylene is introduced for the addition reaction, raw materials are clean and free from pollution, introduction of highly toxic sodium cyanide is avoided, the total yield is high, and the albendazole synthesis method has a good industrialization prospect.
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- Microwave-Assisted Nickel-Catalyzed Synthesis of Benzimidazoles: Ammonia as a Cheap and Nontoxic Nitrogen Source
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An efficient and convenient Ni-catalyzed C-N bond formation for the synthesis of various benzimidazoles from various 2-haloanilines, aldehydes, and ammonia in a concise manner is reported. This protocol uses commercially available, nonhazardous, clean ammonia as a reaction partner instead of other nitrogen sources. Benzimidazoles, as the sole products, were obtained in high to excellent yields (up to 95%).
- Ke, Fang,Zhang, Peng,Xu, Yiwen,Lin, Xiaoyan,Lin, Jin,Lin, Chen,Xu, Jianhua
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supporting information
p. 2722 - 2726
(2018/12/14)
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- Synthesizing method of [5-(rosickyite)-1H-benzimidazole-2-radical]methyl carbamate
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The invention discloses a synthesizing method of [5-(rosickyite)-1H-benzimidazole-2-radical]methyl carbamate. The method comprises the following steps: 1) making methyl-benzimidazole-2-methyl carbamate, concentrated sulfuric acid and a nitrating agent to react for 2-10 h under the temperature of -10 to 2 DEG C to obtain 5-nitrobenzimidazole-2-methyl carbamate; 2) adding 5-nitrobenzimidazole-2-methyl carbamate, 1-bromopropane or 1-chloropropane, thiosulfate, alkali and copper salt to a solvent A; carrying out a reaction for 5-20 h to obtain albendazole; adding 5-nitrobenzimidazole-2-methyl carbamate, tri-n-propyltin chloride, sulphur, potassium fluoride, alkali and copper salt to a solvent B; stirring and carrying out a reaction for 5-20 h to obtain albendazole; or adding 5-nitrobenzimidazole-2-methyl carbamate, n-propylboronic acid, sulphur, alkali and copper salt to a solvent C; carrying out a reaction for 5-20 h to obtain albendazole. The synthesizing method is short in synthesizingroute, simple in synthesizing and separating, low in risk, environmentally friendly, and safe.
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- A preparing method of albendazole
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A preparing method of albendazole is disclosed. The method adopts 2-nitro-4-thiocyanatoaniline as a raw material, and includes salifying with an aqueous sodium hydroxide solution in an n-propanol solvent under nitrogen protection, reacting with bromopropane, and separating to obtain an n-propanol solution of 2-nitro-4-(propylthio)aniline, and therefore a problem that an impurity that is methyl 5-(methylthio)benzoimidazol-2-yl carbamate in products is high in content because steps of salifying in methanol with sodium sulfide and then reacting with bromopropane in processes at present is overcome. A technique of reducing the 2-nitro-4-(propylthio)aniline by utilizing hydrazine hydrate is adopted to replace a technique of reducing with sodium sulfide at present, thus overcoming a problem that sulfur-containing waste water is high in amount and difficult to treat in the sodium sulfide reduction technique. A methanol solution of methyl O-methyl isourea formate is adopted as a ring closing agent, thus overcoming a problem that waste water is high in amount in processes at present when cyanamide and an aqueous methyl formate solution are adopted as ring closing agents. The method is advantaged by a small waste water amount, capability of being environmental friendly, high product purity, and the like.
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- Method for preparing albendazole with chloropropane in place of bromopropane
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The invention discloses a method for preparing albendazole with chloropropane in place of bromopropane, and belongs to the technical field of synthesis of imidazole compounds. The method comprises the following steps of firstly, sequentially adding carbendazol, sodium thiocyanate and glacial acetic acid into a reactor, performing uniform stirring, raising the temperature to 35 DEG C, slowly and dropwise adding a hydrogen peroxide solution under a stirring state, and performing a reaction so as to obtain solid 5-sulfhydryl benzimidazole-2-carbaminic acid methylester; preparing a chlorobenzene Grignard reagent by using 1,2-bromofume Grignard reagent; and then adding a phase transfer catalyst namely benzyl triethyl ammonium chloride to the solid 5-sulfhydryl benzimidazole-2-carbaminic acid methylester, slowly and dropwise adding a tetrahydrofuran solution of sodium hydride under the stirring state, performing a reaction for 30 minutes, beginning to slowly and dropwise drop the chlorobenzene Grignard reagent under the stirring condition, and performing a reaction so as to obtain an albendazole product. According to the method disclosed by the invention, the chloropropane is used for replacing the bromopropane which is relatively higher in price, so that not only is the investment cost of reaction raw materials reduced, but also the yield and the purity of the albendazole are guaranteed to be increased.
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Paragraph 0010; 0024
(2017/07/01)
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- PROCESS FOR PREPARATION OF ALBENDAZOLE
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The present invention discloses a novel, cost-effective process for preparation of a benzimidazole carbamates compound. Specifically, it relates to the process for the preparation of anti-parasite bulk drug albendazole. The process comprises a) thiocyanating 2-nitroaniline of formula VI with ammonium thiocyanated in presence of a halogen to obtain 2-nitro-4-thiocyanoaniline of formula V; b)propylating 2-nitro-4-thiocyanoaniline of formula V with propylbromide in presence of n-propanol and a base in absence of a phase transfer catalyst to obtain 4-propylthio-2-nitroaniline of formula III; C) reducing the nitro group of 4-propylthio-2-nitroaniline prepared in step b) by reacting an aqueous alkali metal sulphide or an alkaline metal sulphide to obtain 4-propylthio-o-phenylenediamine of formula II; and d)condensing 4-propylthio-o-phenylenediamine of formula II with alkali or alkaline earth metal salt of methylcyano carbamate in presence of an acid to form Albendazole of formula I.
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- A PROCESS FOR PREPARATION OF ALBENDAZOLE
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The present invention discloses a novel, cost-effective process for preparation of a benzimidazole carbamates compound. Specifically, it relates to the process for the preparation of anti-parasite bulk drug albendazole. The process comprises a) thiocyanating 2-nitroaniline of formula VI with ammonium thiocyanated in presence of a halogen to obtain 2-nitro-4-thiocyanoaniline of formula V; b)propylating 2-nitro-4-thiocyanoaniline of formula V with propylbromide in presence of n-propanol and a base in absence of a phase transfer catalyst to obtain 4-propylthio-2-nitroaniline of formula III; C) reducing the nitro group of 4- propylthio-2-nitroaniline prepared in step b) by reacting an aqueous alkali metal sulphide or an alkaline metal sulphide to obtain 4-propylthio-o-phenylenediamine of formula II; and d)condensing 4-propylthio-o-phenylenediamine of formula II with alkali or alkaline earth metal salt of methylcyano carbamate in presence of an acid to form Albendazole of formula I.
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- Synthesis and hydrolytic stability studies of albendazole carrier prodrugs
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Three N-acyl (2, 3, and 4), two N-alkoxycarbonyl (5 and 6), and one N-acyloxymethyl (7) derivatives of albendazole (1) have been prepared and assessed as potential prodrugs. The determination of the aqueous solubility and partition coefficient, as well as the conversion of these derivatives to 1 in buffer solution, human plasma, and pig liver esterase were determined.
- Hernandez-Luis, Francisco,Hernandez-Campos, Alicia,Yepez-Mulia, Lilian,Cedillo, Roberto,Castillo, Rafael
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p. 1359 - 1362
(2007/10/03)
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- 2H-benzimidazoles (isobenzimidazoles). Part 10. Synthesis of polysubstituted o-phenylenediamines and their conversion into heterocycles, particularly 2-substituted benzimidazoles with known or potential anthelminthic activity
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Polysubstituted o-phenylenediamines were synthesised in moderate to high yield by reductive cleavage of the corresponding 2H-benzimidazole-2-spirocyclohexane with sodium dithionite in aqueous ethanol and converted into methyl benzimidazole-2-carbamates and 2-methylthio- and 2-trifluoro-methylbenzimidazoles with known or potential anthelminthic activity. 5-(Pyrimidin-2-ylthio)-benzimidazole and 11-(pyridin-2-ylthio)dibenzo[a,c]phenazine were synthesized too. Attempts to oxidise 1,3-dihydro-2H-4,9-diazanaphth[2,3-d]imidazole, prepared by condensation of 2,3-diaminoquinoxaline with cyclohexanone, to an analogue of the title system failed.
- Hazelton,Iddon,Suschitzky,Woolley
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p. 10771 - 10794
(2007/10/02)
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- 1,5-diphenyl-3-formazancarbonitril parasiticides
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The present invention is directed to the use of 1,5-diaryl-3 -formazancarbonitrile compounds for the control of parasites in vertebrate animals.
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- SYNTHESIS AND REACTIONS OF 2H-BENZIMIDAZOLE-2-SPIROCYCLOHEXANES : AN APPLICATION OF "UMPOLING"
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The title compounds are available through condensation of an o-phenylenediamine with cyclohexanone followed by oxidation of the resulting product with manganese dioxide.In this article we review their oxidation, reduction, and rearrangement reactions along with their reactions with nitrogen, oxygen, sulphur, and other nucleophiles.As well as the parent compound the reactions of the 5-chloro-, 5,6-dichloro-, 4,6-dibromo-, 5-phenylsulphonyl- and 5-methoxy-derivative are discussed in some detail.Some applications of the methodology developed, particularly to the synthesis of actual or potential benzimidazole anthelminthics, are given also.
- Iddon, Brian
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p. 673 - 701
(2007/10/02)
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- Process for preparing thio, dithio or carbonyl compounds
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A process is disclosed for the preparation of compounds of the Formula I wherein X is thio, dithio or carbonyl and R and R1 are defined hereinbelow which comprises reducing a compound of the Formula II wherein A is chlorosulfonyl or a group of the Formula STR1 with a sulfur compound comprising sulfur which is of the (+)4 oxidation degree and is converted into the (+)6 oxidation degree during the process or with a sulfur compound which is decomposed in acidic medium to a compound of the latter oxidation degree in the presence of a catalytic amount but not more than 0.5 mole--related to 1 mole of the starting material of the Formula II--of elemental iodine or a compound capable of delivering hydrogen iodide in acidic medium or a compound which can be reduced to hydrogen iodide in acidic medium with the sulfur compound used.
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- Process for the preparation of benzimidazole-thiol
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A new process is disclosed for preparing a compound of the formula (I) STR1 wherein R is C1 to C5 alkyl; which comprises reducing a compound of the formula (II) STR2 or salt thereof wherein A is --SO2 X, --SOH, --SOA1, or --SA1 group, X is chlorine or hydrogen; and A1 is a group of the Formula STR3 with the aid of aluminum activated with a catalytic amount of a metal and/or metal salt in a mixture of water, a mineral acid, and an aliphatic carboxylic acid having 1 to 3 carbon atoms at a temperature of 0° to 100° C., thereafter, optionally, the product is recovered from an acid medium at a pH range of 2 to 3 in crystalline form.
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- Process for preparing alkylthiobenzimidazoles
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The invention concerns a new process for the preparation of biologically active 2-[(alkoxycarbonyl)amino]-5-(alkylthio)-1H-benzimidazoles of the general formula (V) STR1 wherein R and R1 independently stand for alkyl having 1 to 3 carbon atoms.
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