Catalystfree synthesis of benzodiazepines and benzimidazoles. Benzodiazepines are widely used drugs for several indications. The product was then analyzed using thin layer chromatography tlc and melting point determination. Silica gel was found to be an effective support for the synthesis of 1,5.
Different benzodiazepine drugs have different side groups attached to this central structure. The catalytic activity of developed nanocatalyst was investigated for the synthesis of 1,4 benzodiazepines derivatives via the threecomponent condensation of ophenylenediamine 2, dimedone 33 and various aldehydes under solvent free conditions. A novel, facile and efficient methodology for the synthesis of 1,5benzodiazepines by the reaction of chalcone with 1,2phenylenediamine with the mediation of sulfurdoped graphene is described. An efficient and simple environmentfriendly method for the preparation of substituted 1,5benzodiazepines as biologically interesting compounds under heterogenous catalyst is described. In the green circles are benzene rings and in the red circle is a diazepine ring, with the whole 1,4benzodiazepine system being in the blue ring the 1 and 4 denote the position of the nitrogen atoms in the ring. The present protocol features mild reaction conditions, high yields and feasibility of large. In all the cases, the reactions are highly selective and are completed within h. Design and synthesis of novel benzodiazepines stephanie lee macquarrie abstract bivalent drug design is an efficient strategy for increasing potency and selectivity of many drugs. Synthesis of spiroindolo1,5benzodiazepines from 3acetyl coumarins for use as possible antianxiety agents. Synthesis the synthesis strategy for constructing the annulated pyrrolo1,4benzodiazepines derivatives 16 is shown in scheme 1. Importantly, benzodiazepines are finding resurgence in medicinal chemistry with new indications such as anticancer therapeutics. Synthesis of 1,5benzodiazepine and its derivatives by condensation reaction using hmcm22 as catalyst. Synthesis and anticonvulsant activity of various mannich. Jan 15, 2012 benzodiazepines augment the effects of gabagaba is the main inhibitory neurotransmitterin the brain.
Synthesis of spiroindolo1,5 benzodiazepines from 3acetyl coumarins for use as possible antianxiety agents. Withdrawing benzodiazepines dont stop bzds abruptly due to risk of withdrawal seizures strategy 2 substitute and taper principles of addiction medicine. Benzodiazepine metabolism active metabolite desmethyldiazepam oxazepam conjugation glucuronidation urinary excretion diazepam temazepam amino metabolite desmethyl metabolite amino metabolite flunitrazepa m clonazepam alprazolam a hydroxymetabolites nitrazepam metabolites lorazepam alprazolam. An efficient and simple environmentfriendly method for the preparation of substituted 1,5 benzodiazepines as biologically interesting compounds under heterogenous catalyst is described. Synthesis, anticonvulsant, sedative and anxiolytic activities. Reaction of 1,4benzodiazepinic nnitrosoamidines, used as synthetic equivalents of imidoyl chlorides, with the monoanion of tosylmethyl isocyanide is described. Benzodiazepines have a various behavioral effects in addition to their anxiolytic action.
Application of chalcone in synthesis of new heterocycles. This simple and efficient method furnishes the corresponding 1h1,5 benzodiazepines and 1,2disubstituted benzimidazoles in good yields by the condensation of ophenylenediamine with several ketones and aldehydes, respectively. Solventfree syntheses of 1,5benzodiazepines using hy. A study of some of the reactions involved in the synthesis of. These systems can be derivatized to the corresponding trisubstituted 1,4 benzodiazepines by alkylation or acylation of the imidazole ring. May 28, 2012 during our studies on the application of silica resin with acid functional moieties, we found that sio 2 h 2 so 4 mixture is a simple and efficient catalyst for solvent free synthesis of 1,5 benzodiazepines under microwave irradiation, as it was followed in figure 1. Graphite oxide go, an attractive metal free carbocatalyst, was employed as a green and highly efficient catalytic system for the synthesis of 1,5benzodiazepines.
Benzodiazepines constitute an important class of biologically active compounds and their synthesis has been receiving much attention in the field of medicinal and pharmaceutical chemistry owing to their application as anticonvulsant, antiinflammatory, analgesic, hypnotic, and sedative agents and to their hypnotic activity 16. Benzodiazepines bzd, bdz, bzs, sometimes called benzos, are a class of psychoactive. A study of some of the reactions involved in the synthesis. We described herein the use of glycerol as solvent in the catalyst free synthesis of benzodiazepines and benzimidazoles. Pdf highly efficient zinc oxide nanoparticles catalyzed. An efficient, recoverable and reusable solid acid catalyst for the solventfree synthesis of benzodiazepines volume. Benzothiazepines and benzodiazepines on inorganic supports. An update on the synthesis of pyrrolo1,4benzodiazepines mdpi. The process gives entry to 34tosylimidazo1,5a1,4 benzodiazepines, compounds which have not been described yet in the literature. From the general scheme as given above its synthesis preparation has a common strategy wherein, triazol ring formation is a common step. We herein report a simple efficient method of oxidative heterocyclization reaction of 2hydrazino1,4benzodiazepines with various aldehydes in presence of dib diacetoxyiodobenzene. The first such drug, chlordiazepoxide librium, was discovered accidentally by leo sternbach in 1955, and made available in 1960 by hoffmannla roche, which, since 1963, has also marketed the benzodiazepine diazepam.
The advantages of this protocol are operational simplicity, nontoxicity, low cost, easy recovery, and an environmentally benign nature. During our studies on the application of silica resin with acid functional moieties, we found that sio 2 h 2 so 4 mixture is a simple and efficient catalyst for solventfree synthesis of 1,5benzodiazepines under microwave irradiation, as it was followed in figure 1. A general method is provided for the synthesis of substituted 2,3dihydro5phenyl1h1,4 benzodiazepines by the reaction of bistrifiated2,5dihydroxy benzophenones with 1,2bisaminoethanes, followed by displacement of the 7trifloxy group. Pdf a simple and versatile method for the synthesis of 1,5benzodiazepines is via. The purpose of this experiment was to synthesize the heterocycle benzodiazepine from orthophenylenediamine and acetone. Benzodiazepines all benzodiazepines have a benzene ring attached to a diazepine ring. Pdf on nov 5, 2018, elisabet batlle and others published 1. This simple and efficient method furnishes the corresponding 1h1,5benzodiazepines and 1,2disubstituted benzimidazoles in good yields by the condensation of ophenylenediamine with several ketones and aldehydes, respectively in addition, glycerol can be easily re. A simple and versatile method for the synthesis of 1,5benzodiazepines is via condensation of ophenylenediamines opda and ketones in the presence of catalytic amount of hmcm22 using acetonitrile as solvent at room temperature. Nov 14, 1995 a general method is provided for the synthesis of substituted 2,3dihydro5phenyl1h1,4 benzodiazepines by the reaction of bistrifiated2,5dihydroxy benzophenones with 1,2bisaminoethanes, followe. Benzodiazepines have recently received considerable attention because of their promising biological activities such as anticonvulsant, antioxidant, anthelmintic and antibacterial activiti es 3,4. Benzodiazepines augment the effects of gabagaba is the main inhibitory neurotransmitterin the brain. Catalystfree synthesis of benzodiazepines and benzimidazoles using glycerol as recyclable solvent.
Synthesis of new amino1,5benzodiazepine and benzotriazole. The mixture was stirred for 30 minutes and turned a. Recent advances in synthesis and medicinal chemistry of. Diazepam, first marketed as valium, is a medicine of the benzodiazepine family that typically produces a calming effect. They exert their action only in the presence of gaba for this reason they arecalled positive allosteric modulators pams. While amines may undergo multiuple methylations to form quaternary ammonium salts, the nitrogen atom being akylated in the diazepam synthesis is an amide. It may also be used to cause memory loss during certain medical. The benzodiazepine moiety formulaa required for synthesis can be prepared from corresponding suitable benzophenone derivatives which is. Due to adverse effects associated with the longterm use of benzodiazepines, withdrawal from benzodiazepines, in general, leads. Benzodiazepines benzimidazoles abstract we described herein the use of glycerol as solvent in the catalystfree synthesis of benzodiazepines and benzimidazoles. Other than their biological importance, benzodiazepines are valuable synthons for the preparation of fused ring compounds, such as.
Synthesis, anticonvulsant, sedative and anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, benzodiazepine withdrawal syndrome, muscle spasms, trouble sleeping, and restless legs syndrome. Benzodiazepines bzd, bdz, bzs, sometimes called benzos, are a class of psychoactive drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. Some heterocycles containing benzodiazepines moiety were reported to possess anti inflammatory17, antiviral18, antihiv119, antimicrobial20 and antitumor21 activities. Pyrrolo1,4benzodiazepines are tricyclic compounds that are considered privileged structures since they possess a wide range of biological activities. Modified synthesis and characterization of benzodiazepines. Synthesis of new amino1,5benzodiazepine and benzotriazole derivatives from dimedone norah bennamane, rachedine kaoua, lamouri hammal and bellara nedjarkolli laboratory of applied organic chemistry, university of sciences and technology houari boumediene, bp 32, elalia, algiers, algeria. Replacement of the nnitrosoamidine moiety through treatment with the nucleophiles acetylhydrazine, aminoacetaldehyde dimethylacetal and 1amino2propanol, followed by an acidcatalyzed cyclization step, afforded triazolo and imidazobenzodiazepines 1, 6, and 7, respectively.
We described herein the use of glycerol as solvent in the catalystfree synthesis of benzodiazepines and benzimidazoles. Pdf solvent free oxalic acid catalyzed synthesis of 1,5. Sem, tga, xps and raman tests were used to investigate the morphology, thermal behavior and surface properties of the synthesized graphene. The onepot multicomponent condensation of ophenylenediamine. This process offers an easy and efficient synthesis of substituted 1,5benzodiazepines in high yields. Environmentally clean solvent free processes we have made an attempt to synthesize novel substituted benzodiazepines derivatives by using both microwave assisted as well as conventional synthetic methods.
Benzodiazepines are one of the most commonly prescribed medications to treat anxiety, insomnia, and other conditions in the united states. The use of benzodiazepines bzds in the treatment of posttraumatic stress disorder ptsd is both common and controversial. The process gives entry to 34tosylimidazo1,5a1,4benzodiazepines, compounds which have not been described yet in the literature. Due to their diverse spectrum of biological activities, they were considered as privileged structures in medicinal. A general method is provided for the synthesis of substituted 2,3dihydro5phenyl1h1,4benzodiazepines by the reaction of bistrifiated2,5dihydroxy benzophenones with 1,2bisaminoethanes. Benzodiazepines have recently received considerable attention because of their promising biological activities such as anticonvulsant. An update on the synthesis of pyrrolo1,4benzodiazepines. Thus, acute sedative effects are beneficial when treating sleep disorders but are viewed as a. Rahway, usa were tasked with developing an efficient synthesis of a benzodiazepinebased molecule.
Benzodiazepine drugs are substituted 1,4 benzodiazepines, although the chemical term can refer to many other compounds that do not have useful pharmacological properties. The first benzodiazepine, chlordiazepoxide librium, was synthesized in 1955 by. Considering all the service members returning from afghanistan and. Benzodiazepines bzds represents one of the important and highly explored class of sevenmembered aromatic heterocycles containing two ring nitrogen that are critical for numerous applications in the pharmaceutical industry and organic synthesis of complex molecules. Diazepam synthesis iv by psycho chemist7,8,9 2methylamino5chlorobenzophenone dissolve 400 g sodium hydroxide in 4 l ethanol and in a seperate flask, 1. We herein report a simple efficient method of oxidative heterocyclization reaction of 2hydrazino1,4 benzodiazepines with various aldehydes in presence of dib diacetoxyiodobenzene. Mar 16, 2014 1,5benzodiazepines are synthesized from 1,2diamines and ketones catalyzed by hy zeolite at 50 c under solventfree conditions.
Due to adverse effects associated with the longterm use of benzodiazepines, withdrawal from benzodiazepines, in general, leads to improved physical and mental health. The first encounter with these molecules was the isolation of anthramycin from cultures of streptomyces, followed by determination of the xray crystal structure of the molecule and a study of its interaction with dna. Synthesis of 1,5benzodiazepine and its derivatives by. The reaction was optimized for concentration, solvent, temperature, and reaction time. These systems can be derivatized to the corresponding trisubstituted 1,4benzodiazepines. Benzodiazepines patterns of use bzds are one of the most prescribed drugs 4% of all prescriptions from general practitioners are for benzodiazepines bzds predictors for bzd prescription include. Pdf synthesis of 1,5benzodiazepine and its derivatives by. Interestingly, the sideeffect profile of the acute effects of benzodiazepines varies depending upon the specific therapeutic goal 17.
Solvent free oxalic acid catalyzed synthesis of 1,5benzodiazepines article pdf available in journal of the chilean chemical society 584. We devised a strategy to prepare agonistbenzodiazepine heterodimers that could simultaneously bind to agonist and bzd sites of the gabaar. Synthesis of 72hydroxyphenyl2phenyl4,6dihydropyrazolo4,3b1,4diazepin52hones and 42. The method is applicable to both cyclic and acyclic ketones without.