Letters in Organic Chemistry - Volume 13, Issue 4, 2016

Background: Several crysene derivatives have been prepared using different protocols; however some require special reagents and conditions. The aim of study involved the synthesis of two crysene derivative using androsterone and estrone as chemical tool. Methods: Crysene derivatives were prepared by a series of reactions that involve; 1) Synthesis of two isoquinolinone derivatives by reaction of androsterone or estrone with p-nitrobenzoyl azide using imidazole as catalyst; 2) Reaction of the isoquinoline derivatives with ethylenediamine to form two chrysenol using boric acid as catalyst; 3) Synthesis of chrysene-carbaldehyde derivatives via oxidation of hydroxyl groups from chrysenol derivatives with DMSO; 4) Reaction of chrysene-carbaldehyde derivatives with phenylpropanone to form two chrysene-phenylpropenone analogs; 5) Preparation of chrisene-allylic alcohol derivatives by reaction of chrysene-phenylpropenones with benzaldehyde using imidazole as catalyst; 6) Synthesis of two chrisene-dione derivatives through oxidation of chrisene-allylic alcohols with DMSO; 7) Reaction of the chrisene-diones with ethylenediamine for preparation of two diazepin-chrisene derivatives using boric acid as catalyst. The chemical structure of compounds was determined by spectroscopic and spectrometric methods. Results: The 1H NMR spectrum for the chrysene derivatives showed signals at 4.50-4.76 ppm for azepine rings and at 6.50 and 7.46-8.36 ppm for phenyl groups. Conclusion: In conclusion, in this work were prepared two crysene derivatives using several chemical techniques, which are simple procedures and very ease of workup.

Background: A series of novel 2-methoxy-N-phenyl-6-(5-phenyl-1,3,4-oxadiazol-2- yl)pyridin-3-amine (6a-i) have been synthesized from bromo methoxy picolinicacid as starting material. Finally, oxadiazole was coupled with various anilines using buchwald coupling reactions to give the target compounds. The newly synthesized compounds were evaluated for their efficacy as antimicrobial agents against various Gram-positive and Gram-negative strains of bacteria and fungal strains. Compounds 6h and 6i possessing trifluoromethyl groups at second and fourth positions of the aniline ring exhibited selective inhibition against S. aureus. Amongst these compounds 6c was found to be the most potent against Bacillus subtilis and Candida albicans. Moreover, other compounds also found to be potential antibacterial agents in comparison to the standard drugs. Methods: On the basis of the above findings and in continuation of our search on 1,3,4-Oxadiazole derivatives with potential biological activity, we have synthesized new molecules based on 1,3,4-Oxadiazole ring system by incorporating methoxy pyridine moiety. Results: The synthetic route for the synthesis of title compounds were started with using commercially available acid. In the first place Esterification of starting meterial followed by treating with hydrazine hydrate afforded the compound, which upon reaction with benzoylchloride in the presence of POCl3 furnished oxadiazloe derivatives. Finally, the key intermediates 1,3,4-oxadiazole were coupled with various anilines using buchwald reaction gave the final compounds. The chemical structures of all the newly synthesized compounds were confirmed by their 1H NMR, 13C NMR, mass spectral data and elemental analysis. Further these compounds have been screened for their antibacterial, antifungal and nematicidal activities. Conclusion: Synthesis and screening of antibacterial and antifungal activities for a novel series of 1,3,4-Oxadiazole conjugates have been investigated. All the compounds have shown mild to potent inhibitory activity against B. subtilis and exhibited mild to moderate antibacterial activities against the other tested organisms. Compounds 6c and 6e were found to be the most active against most of the tested organisms. Some of the compounds have shown significant antibacterial activity in comparison to the controls.

An environmentally benign protocol for the synthesis of some new 3, 4-dihydropyrimidin- 2-(1H)-ones and thiones promoted by p-Toulene Sulfonic Acid (PTSA) efficiently catalyzes the three component condensation reaction of formylchromone, substituted acetophenones and urea/thiourea under microwave irradiation (MWI). Compared to the classical Biginelli reaction conditions, this new methodology consistently has the advantage of giving good yields, require less reaction time, mild conditions with simple workup procedure. Newly synthesized compounds show moderate to good antimicrobial properties against some gram positive and gram negative bacteria. Background: During recent years, dihydropyrimidinones have emerged as a vital compound with diverse biological and pharmacological applications. P. Biginelli in 1893 was the first chemist to report the three component condensation, using ethylacetoacetate with different aldehydes and urea for the synthesis of dihydropyrimidine under acidic condition. However, serious drawback of this reaction has been the low yields obtained in the case of substituted aromatic and aliphatic aldehydes. Several improved procedures for the synthesis of dihydropyrimidines have been recently reported to enhance the efficiency of the Biginelli reaction, using various catalysts. Inspite of their potential utility many of the existing methods suffer from some drawbacks, such as the use of strong acidic conditions, long reaction times, tedious workup procedures, posing environmental hazards, and low yield of the products. The present work describes a novel approach toward the solvent-free one-pot synthesis of some novel dihydropyrimidine derivatives using formylchromone, substituted acetophenones and urea/thiourea under Microwave Irradiation (MWI) as well as by conventional method using p- toulene sulfonic acid (PTSA) as catalyst. Objective: To develop an environment friendly method to get high yield and purity for the one-pot synthesis of some novel 3,4-Dihydropyrimidine derivatives. Also, incorporation of various functional groups along with other heterocyclic ring like chromone nucleus has been introduced to increase the efficacy of antimicrobial properties. Methods: Conventional Method: A mixture of 2.24g (0.01mol) 4-Oxo-4-H-benzo[h]chromene-3-carbaldehyde (1) was refluxed for 12-14 h with substituted Acetophenones (0.01mol) (2a: 1.2 mL), m-Nitroacetophenone (2b:1.65 g), p-Chloro acetophenone(2c:1.54 g), p-Hydroxy acetophenone, (2d:1.36 g), p-Bromo acetophenone (2e:1.99 g) and p- Nitroacetophenone(2f:1.65 g) and (0.01mol) of urea(0.60 g)/ thiourea(0.76 g) (3) in presence of p-toulene sulphonic acid (PTSA) (7-10 mol %, 13.3-19 g) as catalyst in 1,4 dioxane (30 mL). After the completion of reaction, the reaction mixture was poured into the cold water, filtered, washed with water, dried and was recrystallized using ethanol: acetic acid (2:1). Microwave Irradiation Method: A mixture of 0.22 g (1 mmol) 4-Oxo-4-H-benzo[h]chromene-3-carbaldehyde (1), substituted acetophenones(1 mmol) (2a:0.12 mL), m-Nitro acetophenone(2b:0.165 g), p-Chloro acetophenone(2c:0.154 g), p- Hydroxy acetophenone(2d:0.136 g), p-Bromo acetophenone(2e:0.199 g) and p- Nitro acetophenone(2f:0.165 g) and (1 mmol) of urea (0.06 g)/ thiourea (0.076 g) (3) in presence of p-toulene sulphonic acid (PTSA) (1-3 mol %, 1.9-6.7 g) was irradiated at 300 W, 120°C for 15-20 min to get 4-(4-Oxo-4H-benzo[h]chromen-3-yl)-6-substituted phenyl-3,4- dihydropyrimidin-2(1H)-one. After the completion of reaction, the reaction mixture was poured into the cold water, filtered, washed with water, dried and was recrystallized using ethanol: acetic acid (2:1). Results: 4-(4-Oxo-4H-benzo[h]chromen-3-yl)-6-substituted phenyl-3,4-dihydropyrimidin-2(1H)-one: 4(a-f) and 3-(6- Substituted phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4yl)-4H-benzo[h]chromen-4-one 5(a-f) were obtained by one-pot three component condensation of 4-Oxo-4-H-benzo[h]chromene-3-carbaldehyde(1), substituted acetophenones 2(a-f) and Urea / Thiourea (3) in presence of p-toulene sulphonic acid (PTSA) as a catalyst under microwave irradiation in solventfree condition. The present method has given excellent yields as compared to conventional method (Table 1). The schematic representation has been shown in Scheme 1. Under these conditions, the time for completion of reaction has been reduced dramatically and completed within 15-20 min as compared with the conventional method consuming 12-14 h to get the desired product. Different substituted acetophenones have been employed in this reaction successfully which showed large scope of this reaction for the synthesis of dihydropyrimidine derivatives. The newly dihydropyrimidines were synthesized by corresponding acetophenones, 4-Oxo-4-H-benzo[h]chromene-3-carbaldehyde and urea/thiourea in 1,4-dioxane using conventional method as well as by green approach under microwave irradiation in solvent free conditions (Scheme 1). The percentage yield has been found to be drastically increased in case of solvent free condition under microwave irradiation. Synthesized compounds have been characterized on the basis of various spectroscopic techniques such as FTIR, HRMS, 1H and 13C NMR. HRMS of the compounds 4c and 5c showed two peaks of M+ Na in a ratio of 3:1 and confirmed the existence of chloro group. Similarly compounds, 4e and 5e showed two peaks of M+ Na peak in a ratio of 100:97.3 nearly 1:1 ratios which confirmed the existence of bromo group. 1H and 13C NMR also gave various corresponding peaks confirming the formation of various DHPMs. To investigate and evaluate the catalytic efficacy of different Lewis acids in this reaction, some other combinations have also been tried (Table 2). It is clear from these data (Table 2) the catalyst PTSA used in this reaction has been found to be most effective in synthesis of dihydropyrimidines with a better yield of the products in a very short reaction time. Other catalysts such as AlCl3.6H2O and ZnCl2 did not give the desired product. This protocol is practically general and several functionalities like nitro, chloro, hydroxyl and bromo were not affected during the course of reaction and were of special interest in the synthesis of dihydropyrimidines in a single step with high yield. An amount of (1-3 mol %) PTSA was found to be very effective under MWI and the use of less than that was not optimal. All the synthesized dihydropyrimidine derivatives 4(a-f) and 5(a-f) were tested for their in vitro antibacterial study against different strains of bacterial species such as S.aureus, B.subtillis, E.coli and K.aerogenes using well diffusion method. Antibacterial results have been summarized in (Table 3), which indicated that the most of the synthesized compounds exhibited moderate to good antibacterial properties against all bacterial strains and compared with standard drug Amoxicillin. Compounds 4b, 4c, 4d, 4e and 5f have exhibited excellent activity against E.coli species. Similarly compounds, 5b and 5f have showed excellent activity against S.aureus and compound 4e showed good activity against B.subtilis. All these compounds showed their activity at the concentration of 100μl. Remaining compounds exhibited moderate antibacterial activity as compared to the standard drug (Amoxicillin). Conclusion: In the course of our study an environment friendly, solvent-free, mild and efficient protocol for the synthesis of some new dihydropyrimidinones and thiones catalyzed by PTSA in MWI have been found to be of several advantages. It may be of high interest for a synthetic chemist for its simple and environmentally safe procedure. It has an easy workup with mild conditions, solvent-free, short reaction times (15-20 min) and produced excellent yields (80-95%). Furthermore, this series may provide new classes of biologically active compounds. The newly synthesized DHPM’s showed moderate to good antimicrobial properties. Therefore, we expect our protocol will find its way to endow the requirements of pharmaceutical industries and institutions towards the invention of broad range of dihydropyrimidones and open a new pathway in the field of green chemistry which is the need of hour.

Background: Thiazoles and their derivatives are attracting continuing interest over the years because of their varied biological activities. Thiazole and in particular the 2-amino thiazole moiety has been incorporated into a wide variety of therapeutically interesting candidates including antibacterial, anti-HIV, hypertension, anti-inflamenmatory, anti-viral and anticancer agents. Methods: Several methods for the synthesis of thiazole derivatives have been developed. The most widely used method being the Hantzch’s synthesis. In this paper, we describe an efficient one-pot method for the synthesis of some thiazolidin-2-ylidene benzamide and aminothiazole derivatives via condensation of 3-aminopyridine or 2- aminopyridine with phenacyl bromide and benzoyl isothiocyanates. Results: The reaction of 3-aminopyridine, benzoyl isothiocyanates, and phenacyl bromide in the presence of triethylamine yields thiazolidin-2-ylidene benzamides, which upon heating in acetic acid produce pyridyl aminothiazole derivatives. Also the pyridyl aminothiazole derivatives were obtained by the reaction of 2-aminopyridine with benzoyl isothiocyanates and phenacyl bromide in the presence of triethylamine. The molecular structures of the 4-chloro-N-(4-hydroxy-4-phenyl- 3-(pyridin-3-yl)thiazolidin-2-ylidene)benzamide, phenyl(4-phenyl-2-(pyridin-3-ylamino)thiazol-5-yl)methanone and (4- phenyl-2-(pyridin-2-yl amino)thiazol-5-yl)(o-tolyl)methanone, have been fully determined by means of single crystal Xray diffraction methods. Conclusion: In summary, present study reports one-pot synthesis of thiazolidin-2-ylidene substituted benzamide and pyridyl aminothiazole derivatives via condensation of 3-aminopyridine or 2-aminopyridine with phenacyl bromide and substituted benzoyl isothiocyanates. The single crystal X-Ray diffraction analysis reveals unequivocally the exact identity of the compounds.

Background: Structural distortions due to hyperconjugation in organic molecules, like norbornenes, are well captured through X-ray crystallographic data, but are sometimes difficult to visualize especially for those applying chemical knowledge and are not chemists. Methods: Crystal structure from the Cambridge database were downloaded and converted to .stI format. The structures were then printed at the desired scale using a 3D printer. Results: Replicas of the crystal structures were accurately reproduced in scale and any resulting distortions were clearly visible from the macroscale models. Through space interactions or effect of through space hyperconjugation was illustrated through loss of symmetry or distortions thereof. Conclusion: The norbornene structures exhibits distortion that cannot be observed through conventional ball and stick modelling kits. We show that 3D printed models derived from crystallographic data capture even subtle distortions in molecules. We translate such crystallographic data into scaled-up models through 3D printing.

Background: Marrubium vulgare is used in traditional medicine in some countries such as Jordan in the treatment of diabetes and wounds. The plant is reported to possess vasorelaxant, antihypertensive, analgesic, anti-inflammatory and antioxidant properties. Earlier phytochemical investigations of M. vulgare led to the characterization of the diterpene marrubiin (2) which is the major constituent of the plant [8], and exhibits potent antinociceptive properties and vasorelaxant activity, marruboside and marrubic acid. The aim of this work is to isolate and identify new compounds from Jordanian M. vulgare. Method: The crude ethanolic extract of air- dried defatted whole plants was partitioned into aqueous methanol (MA), butanol (MB) and hexane extracts. The aqueous methanol and butanol extracts were chromatographied on a silica gel columns. Each fraction was purified by a combination of CC, TLC and/ or recrystalization using suitable solvent systems to produce 10 compounds. NMR, MS, and UV spectral analyses were used for structure elucidation of the isolated compounds. Results: The methanol extract yielded eight pure compounds, which were identified as the new compound apigenin7-O- (3",6"- E-p-dicoumaroyl)-β-glucoside 1 and the known compounds marrubiin 2, the major constituent of Marrubuim vulgare, pectolinarigenin 3, apigenin-7-methyl ether 4, labd-13(14)-en-9a, 15, 16-triol 5, apigenin 6, β-sitosteryl glucoside 7, apigenin-7-O-(6"-O- E-p-coumaroyl)-β-glucoside 8. In a similar manner, the butanol extract (MB) was treated as mentioned with the (MA) extract and the resulting fraction afforded the two known compounds: luteolin-7-O-glucoside 9 and acteoside 10 which is reported for first time from Marrubium vulgare. Conclusion: The treatment of the air- dried defatted whole plant of Marrubium vulgare led to the isolation of ten pure compounds, two of them were isolated for the first time from this plant: apigenin7-O-(3",6"- E-p-dicoumaroyl)-β- glucoside 1and acteoside 10.

Background: Cancer is a major health problem worldwide, the relative mortality rate caused by cancer is still very high in developed countries. Although the remarkable success has been achieved: more than 15 small molecule anticancer agents have been approved by the U.S. Food and Drug Administration (FDA) in clinics and dozens are currently in clinical trials, cancer chemotherapy is still highly inadequate, and it is essential to find novel structures, low side effect and more potent anticancer agents. Metronidazole derivatives exhibited widely biological activities, such as: antibacterial, antiinflammatory, anti-parasitic, α-glucosidase inhibition, antitubercular, antimycobacterial, antimicrobial, and anticancer activity. Based on our previous research, we synthesized a series of metronidazole derivatives in current work for the development of anticancer agents. Methods: The target compounds were prepared by the reaction of metronidazole with the R-substituted-pyridine-carboxyl acid in dry THF, catalyzed by DCC, HOBt/DMAP. And then, the in vitro anticancer efficacy against A549, HCT116 and MCF-7 cell lines was evaluated, and the anticancer efficacy was comparable with the reference drug gefitinib. Results: The structures of the target compounds were fully characterized using NMR, MS and XRD. The biological evaluation showed that all compounds exhibited good anticancer activity against A549, HCT116 and MCF-7 cell lines. Conclusion: From these biological results, we can get some rules: (1) The derivatives of carboxyl group at the 3-position of pyridine ring are much stronger than others (carboxyl group at the 4-position and 2-position of pyridine ring); (2) Introduction of the large volume group at the pyridine ring will improve the anticancer efficacy too much. This guidance helps us to design and synthesize more metronidazole derivatives for development of anticancer agents.

Background: Benzodiazaphosphorines have many biological activities such as fungicidal and antitumor. In this work we are interested to synthesize them in order to test their activities in future work. The probable mechanism of obtained benzodiazaphosphorines is discussed. Methods: The obtained benzodiazaphosphorines were characterized using FT-IR, NMR 1H and 13C spectroscopy and elemental analysis. Results: A series of new benzodiazaphosphorines products synthesized were purified by crystallization and obtained with good yields. Conclusion: In this paper we have synthesized a series of benzodiazaphosphorine and benzodiazaphosphorine sulfide which are identified using FT-IR, NMR spectroscopy and elemental analysis. The prepared compounds will be subsequently studied in order to tested their biological activities

Background: With growing interest in developing environmentally friendly reactions and atom-economic processes in recent years, the utilization of water as a solvent has attracted a great deal of attention. This is not only for its low-cost, safe and environmentally benign nature, but also the unique properties of water in promoting reactions. Moreover, it may afford new access to the compounds that required harsh reaction conditions under traditional approaches. The aldol reaction is one of the most useful and widely employed methods for carbon - carbon bond formation in organic synthesis. Aldols can be acted as the raw materials used for the production of lubricants, surface coatings, synthetic resins and the important intermediates in the synthesis of polyols. Methods: p-nitrobenzaldehyde (100 mg), acetone (1.5 ml) and water (2 ml) was added into a round bottom at N2 atmosphere. The suspension was stirred vigorously at 50°C for 48 h. Then the reaction mixture was diluted with brine (10ml) and extracted with 3 × 15 ml ethyl acetate. The organic layer was dried over anhydrous MgSO4. Then the ethyl acetate solution was filtered and evaporated in vacuum. The crude mixture was purified by flash column chromatography on silica gel using petroleum/ ethyl acetate (2/1) as the eluent to give the desired aldol product in 92.0%. All the compounds were spectroscopically characterized (IR, 1H NMR). Results: In the examination of electron-withdrawing groups, a pronounced steric effect was more evident in the ortho position than other positions of nitrobenzaldehydes. The electronic effect influenced the reactions dramatically. No reaction progress was detected when p-methyl benzaldehyde was employed in the identical reaction condition. With increase of carbon number of ketones the yields decreased noticeably, although the temperature was elevated to reflux situations. This was partially for the increase of substrate’s steric bulk. When the acetyl benzene was used as substrate, the reaction gave poor yield. Compared to acetone, cyclic ketones reacted more slowly in reactions. When cyclic ketones were used as substrate at 50°C, only trace amounts of the desired product were obtained. Luckily, when increasing the reaction temperature to reflux conditions, for cycloheptanone, cyclohexanone and cyclopentanone, the yields reached to 86.1%, 91.4% and 56.1% respectively. The decrease was possibly due to the influence of ring strain. More interestingly, an excellent yield was obtained when 4-methylcyclohexanone was used in the reaction. In addition, nicotinaldehyde was used to react with cyclohexanone and afforded the target product in a good yield. Conclusion: In summary, a new methodology has been developed using water as solvent and promoter that is associated with non-flammable, non-toxic reaction medium, mild conditions, easy operation and good yields. The attractive function of water in aldol reaction was observed compared with many organic solvents. The approach was expanded successively to a wide range of substrates, especially cyclic ketones.

Background: Traditional Chinese medicines have attracted increasing interest as potential sources of novel drugs with a wide range of biological and pharmacological activities. The leaves of Antidesma acidum Retz. were used in traditional medicine for treatment of stomachache of children, digestion related issues and diabetes. Moreover, phytochemical investigations of this plant confirmed the presence of alkaloids, triterpenes, and flavonoids. Methods: Using chromatographic methods to isolate compounds from the methanol extract of the leaves of A. acidum. The cytotoxic activities of compounds were evaluated by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, compounds showed significant cytotoxic activity were chosen for further study apoptosis characteristics. Results: Five carbazole alkaloids, clauszoline B (1), clauszoline H (2), mukonal (3), 7-methoxymukonal (4), and heptaphyline (5) and three coumarin derivatives, 5-demethyltoddaculin (6), xanthoxyletin (7), and alloxanthoxyletin (8) were isolated from the leaves of Antidesma acidum. Compounds 1 and 4 exhibited the significant cytotoxic activity on HL-60 with the IC50 values of 4.8±0.2 and 8.0±0.9 μM, respectively. These compounds did not inhibit the growth of HEL-99 normal cell line. The further test indicated compound 1 induced apoptosis via alteration of expression of apoptosis-related proteins and decreased phosphorylation of AKT in HL-60 cells. Conclusion: The results suggested that the constituents from Antidesma acidum may contain effective compounds which can be used as anticancer agents.

Backgroung: A new bile acids conjugates have been obtained from 3α-bromoacetoxy derivatives of lithocholic, deoxycholic and cholic acids with salicylic, acetylsalicylic or nicotinic acids. These new conjugates were confirmed by spectroscopic (1H-, 13C NMR, FT-IR) analysis, mass spectrometry (ESI-MS) and semiempirical methods (PM5) as well as in silico (PASS) studies. Methods: This work reports an original synthesis and physicochemical properties of new conjugates of bile acid derivatives with salicylic (SA), acetylasalicylic (ASA) or nicotinic (NA) acids. The 3α- bromoacetates of bile acids were prepared with good yield according to the literature procedures. The structures of all synthesized compounds were determined from their 1H- and 13C-NMR, FT-IR as well as ESI-MS spectra. Moreover, PM5 calculations were performed on all the products. Additionally, in silico studies PASS (Prediction of Activity Spectra for Substances) were performed for all compounds. Results: The direct alkylation reaction of the carboxylate ions from SA, ASA or NA with methyl litocholate 3α- bromoacetate, methyl deoxycholate 3α-bromoacetate and methyl cholate 3α-bromoacetate with a catalytic amount of 1,8- diazabicyclo[5.4.0]undec-7-ene (DBU) in dry toluene is reliable and simple. This esterification method enables to obtain stable esters with very good yields and without any decomposition, e.g. decarboxylation or other degradation processes. The most frequently predicted types of biological activity (than 90%) are: cholesterol antagonist, antihypercholesterolemic, alkenylglycerophosphocholine hydrolase inhibitor and hypolipemic. The synthesised steroidal conjugates were characterised by 1H and 13C NMR as well as FT-IR spectroscopy. The lowest HOF values were observed for cholic acid derivatives. The number of hydroxyl groups in the bile acid skeleton lowers the value of the determinant of HOF. In addition HOF lowest values observed for conjugates with aspirin. This can be explained by reducing the reactivity of the phenol group of salicylic acid. Hydrogen bonding between hydroxyl group of cholic acid and carbonyl group of aspirin also reduces HOF. This fact can be explained by reduction of electrostatic and steric interactions between the steroid skeletons. Conclusion: In conclusion, nine new conjugates of bile acids were prepared from methyl litocholate 3α-bromoacetate, methyl deoxycholate 3α-bromoacetate and methyl cholate 3α-bromoacetate with a salicylic acid (SA), acetylsalicylic acid (ASA), as well as nicotinic acid (NA) with catalytic amount DBU in dry toluene at 95°C for 24 hours. All new compounds were characterized by 1H NMR, 13C NMR, FT-IR as well as ESI-MS. Molecular structure of all conjugates was performed by PM5 semiempirical method. Additionally, analyses of the biological prediction activity spectra for conjugates of bile acids with SA, ASA and NA prepared herein are examples of in silico studies of chemical compounds. Estimation of the pharmacotherapeutic potential has been accomplished for the synthesized compounds on the basis of Prediction of Activity Spectra for Substances (PASS). Given the a combination of two types of biologically active compounds these conjugates may find applications in medicinal chemistry, biology, and in pharmacology.

Background: Pyrazole is a simple aromatic ring an organic compound of the heterocyclic series that characterized five-membered ring structure which comprises located adjacent two nitrogen atoms and three carbon atoms. In recent years interest in the pyrazole chemistry excessively has increased due to many a wide range of properties. Because they have a wide range of specific properties such as biological activities, pharmaceutical i.e., Pyrazoles were also applied successfully in many fields; medicine, agricultural, industry, pharmaceutical chemistry so that pyrazole chemistry was quite an interesting area of research for the synthesis of their derivatives and investigates new methods. Methods: Research and online content related to synthesis pyrazole and electrophilic cyclization of molecules are reviewed. Excerpts are used to illustrate key themes about chemistry of organic substances bearing pyrazole group. All the solvents and chemical materials were purchased. All the reagents were used directly without purification. Results: The new substitute α,β-alkynic hydrazones was prepared by heating directly from thiophene-2-acetyl chloride and terminal alkyne via a palladium-catalyzed coupling reaction then a series of the new substituted pyrazole derivatives were converted via electrophilic cyclization by catalyst and characterizations of each compound were indicated by the help of spectral data. Conclusion: The new different substitute pyrazoles were synthesized via copper mediated electrophilic cyclization. Firstly, the various hydrazones derivatives were carried out by the condensation reactions of the propargyl ketone that prepared from phenyl acetylene and acyl chloride with hydrazines. The various pyrazoles contain that thiophene were obtained by electrophilic cyclization copper(I) iodide and the various hydrazones. In addition, synthesized of substitute pyrazoles may be apply the other fields because of their diverse and potent biological properties. For this reason, the syntheses of different pyrazole compounds are becoming more importance.

Background: The indole ring system and 4H-Pyran derivatives are significant components in many drugs and pharmaceutical agents and spirooxindole containing both indole and pyran rings have been shown to possess a wide biological and pharmaceutical properties. Methods: We synthesized new derivatives of spirooxindole by a three-component reaction of isatin derivatives, malononitrile (or ethyl cyanoacetate) and beta-dicarbonyl compounds in the presence of catalytic amount of N-Phenylpiperazine (NPP) as an organocatalyst. Results: A series of novel derivatives of spirooxindole with potential biological properties were synthesized by a threecomponent reaction in the presence of catalytic amount of N-Phenylpiperazine (NPP) as an organocatalyst. NPP as an efficient catalyst can be easily handled and removed from the reaction mixture by simple filtration. Compared with the other catalysts, NPP, not only produce equal or better results in terms of reaction time, but also give good to excellent yield of products, thus we introduce it as an efficient catalyst in Knoevenagel condensation and Michael addition reaction. Conclusion: We have described a novel and efficient catalytic method for the synthesis of spirooxindole derivatives. Mainly, valuable features of this method include the excellent product yields, broader substrate scope, high reaction rates and easy workup procedure, which make it a useful and attractive process for the synthesis of these important compounds.