Regioisomeric Compounds Research Articles

GC–MS and GC–IR of regioisomeric 4-N-bromodimethoxybenzyl derivatives of 3-trifluoromethylphenylpiperazine

The seven regioisomeric N-bromodimethoxybenzyl derivatives of 3-TFMPP were synthesized via reductive amination of the seven commercially available bromodimethoxybenzaldehydes. The capillary GC elution profiles for these compounds generally follow the degree of methoxy group substituent crowding on the aromatic ring. The electron ionization mass spectra show a series of major fragment ions common to all seven regioisomeric compounds. The base peak in the EI mass spectra for many of the seven regioisomers occurs at m/z 229 and is the result of contributions from two isobaric fragments, the trifluoromethylphenylpiperazine cation as well as the 79Br bromodimethoxybenzyl cation. Several low intensity ions are related to the specific regioisomeric substitution patterns for the bromodimethoxybenzyl moieties and provide some differentiation for this set of seven compounds. These unique ions allow the seven compounds to be divided into sub-groups and in some cases allow specific isomer identification from only the EI-MS data. The 950 cm−1 to 550 cm−1 lower portion of the fingerprint region in the vapor phase infrared spectra can be used to identify each of the bromodimethoxybenzyl regioisomers after EI-MS fragmentation patterns provide focus on the individual structural sub-groups of compounds in this study.

Syntheses and Room Temperature Phosphorescence Properties of Dibenzobenzodithiophenes and Dibenzothiophenes

Abstract A new family of heavy-atom-free room-temperature phosphorescent compounds, dibenzobenzodithiophenes (DBDTs) have been synthesized and characterized. The afterglow of the regioisomeric compounds has been investigated in a polymer matrix. Furthermore, it has been revealed that much simpler dibenzothiophenes display room-temperature phosphorescence in a polymeric matrix.

Synthesis and Structural Determination of Two New tri-Heterocyclic Regioisomeric Compounds, Precursors of Bi-Triazolic α-Amino Acids, via a Comparative Study using 1D NMR Spectroscopy

In this article, we describe the synthesis of two new triheterocyclic regioisomers, named 4-({4-[(1H-1,2,4-triazol-1-yl)methyl]-1H-1,2,3-triazol-1-yl}methyl)-4-ethyl-2-phenyl-4,5-dihydrooxazole and 4-({5-[(1H-1,2,4-triazol-1-yl)methyl]-1H-1,2,3-triazol-1-yl}methyl)-4-ethyl-2-phenyl-4,5-dihydrooxazole. The action of 1-(propargyl)-1H-1,2,4-triazole on 4-(azidomethyl)-4-ethyl-2-phenyl-4,5-dihydrooxazole, in a very small quantity of toluene, led after 48 hours at 120 °C to two regioisomers with an overall yield of 90%. The allocation of structures to these two regioisomers was carried out based on a comparative spectroscopic study using 1D NMR of the proton and carbon 13, as well as based on data from the literature concerning the cycloaddition reaction.

GC–MS analysis of N-(bromodimethoxybenzyl)-2-, 3-, and 4-methoxyphenethylamines: Inverse analogues of the psychoactive 25B-NBOMe drug

The substituted phenethylamine analogues in this study are derivatives of N-(2-methoxybenzyl)-4-bromo-2,5-dimethoxyphenethylamine (25B-NBOMe) having the reverse substitution pattern for the two aromatic rings. These compounds contain only a single methoxy substituent in the phenethylamine part, and a bromodimethoxy substitution pattern in the benzyl portion. The regioisomers were prepared with variations in the substitution pattern in both the bromodimethoxy substitution pattern of the benzyl part as well as the methoxy substitution pattern in the phenethylamine part. The nine regioisomeric compounds were prepared from the regioisomeric 2-, 3-, and 4- methoxyphenethylamines via N-reductive alkylation with the three regioisomeric 2,4,5-substituted bromodimethoxybenzaldehydes.The EI-MS spectra of these regioisomers gave two major bromine containing ions at m/z 229/231 (base peak) and 258/260 and two non-brominated fragments at m/z 91 and 121. The relative abundance of the m/z 91 was higher for the 2-methoxyphenethylamine substituted isomers and the relative abundance of the m/z 121 fragment was higher in the 4-methoxy substituted isomers. The gas chromatographic separation for the regioisomeric methoxyphenethylamines of each bromodimethoxybenzyl aromatic ring substitution pattern showed the 2-methoxyphenethylamine substituted isomer eluted first followed by the 3-substituted isomer and the 4-methoxyphenethylamine substituted isomer was the last to elute and the three bromodimethoxybenzyl regioisomers for the 2-methoxyphenethylamine subseries were resolved as the trifluoroacetamides. The EI-MS for the TFA derivatives of the 2-bromo-4,5-dimethoxybenzyl substituted isomer gave unique fragment ions resulting from displacement of bromine from the molecular ion. This fragmentation pathway was confirmed using the model compounds N-(2-, 3- and 4-bromobenzyl)phenethylamine trifluoroacetamides.

Vapor phase infrared identification of regioisomeric N-(dimethoxybenzyl)-4-iodo- and 4-bromo-2,5-dimethoxyphenethylamines

Vapor phase infrared spectroscopy provides data for the differentiation of the individual regioisomers of the six N-(dimethoxybenzyl)-4-iodo-2,5-dimethoxyphenethylamines and the six N-(dimethoxybenzyl)-4-bromo-2,5-dimethoxyphenethylamines. These compounds differ from the traditional N-(2-methoxybenzyl)-4-iodo- and 4-bromo-2,5-dimethoxyphenethylamines (25I- and 25B-NBOMe) by the addition of one methoxy group into the N-methoxybenzyl molecular framework. The vapor phase infrared spectra obtained directly as the compounds elute from the GC column provide data for the identification of any one of these regioisomeric compounds to the exclusion of the other five substances of mass spectral equivalence. The spectra are derived from the compounds in the free base form at temperatures preventing interference from water vapor, intermolecular interactions such as polymorphism or other related issues of salt form and/or relative crystallinity. Fragment ions in the electron ionization mass spectra of these compounds identify the nature of the halogen (I or Br) but not the position of substitution of the methoxy groups on the benzyl aromatic ring.These compounds are composed of two separate and distinct ring systems, the halogenated phenethylamines 4-iodo-2,5-dimethoxyphenethylamine and 4-bromo-2,5-dimethoxyphenethylamine and a second ring system consisting of the six positional isomers of dimethoxybenzylamine. Major absorption bands resulting from aromatic ring C–C and C–O stretching vibrations provide data for differentiation of the benzyl ring substitution pattern. Model compounds representing all the single ring systems provide significant structural correlation with the vapor phase infrared spectra for these regioisomeric NBOMe derivatives.

Vapor phase GC-IR identification of regioisomeric N-methoxybenzyl-4-substituted-2,5-dimethoxyphenethylamines (NBOMe)

The common NBOMe drugs of abuse, N-(2-methoxybenzyl)-4-iodo-2,5-dimethoxyphenethylamine (25I-NBOMe) and N-(2-methoxybenzyl)-4-bromo-2,5-dimethoxyphenethylamine (25B-NBOMe), can be differentiated from their corresponding 3- and 4-methoxybenzyl isomers by gas chromatography with vapor phase infrared spectroscopy. The mass spectra for these regioisomeric compounds are essentially identical providing only the identity of the halogen but no specific ions to identify the methoxy group position on the benzyl aromatic ring. The bands from single ring model compounds 2C-B, 2C-I, and all three positional methoxy substituted benzylamines were used to assign each vapor phase absorption band to either the halogenated 2,5 dimethoxybenzene ring or the methoxybenzylamine ring.A pair of aromatic ring stretching bands reflect the position of methoxy group substitution on the benzyl aromatic ring. The 1608 cm−1 band is specific for the two regioisomeric 4-methoxy-benzylamine isomers and this band occurs at 1593 cm−1 for the 2-methoxy isomer in both the 25I and 25B series and shifts to1597/1598 cm−1 for 3-methoxybenzyl 25I and 25B. Asymmetric aryl-O stretching frequencies shift with a change in methoxy substitution around the benzyl aromatic ring (Ring 2) and occur at 1237/1238 cm−1 for ortho, 1261 cm−1 for meta, and 1246 cm−1 for the para isomers. The overall shape and relative intensities of numerous bands in the vapor phase spectra provide clear identification for the individual methoxybenzyl isomers for the 25I-NBOMe and 25B-NBOMe series.

On the Two-Route Mechanism of the Reaction of 1-Alkenes with EtMgX Catalyzed by TaCl5

The reaction of 1-alkenes with C2D5MgBr in the presence of TaCl5 has been studied. Basing on the distribution of the deuterium label in the alkyl chain of the regioisomeric organomagnesium compounds, a tentative mechanism of their formation as key intermediates of 3-substituted tantalocyclopentanes has been proposed. The energy profiles of the reactions of carbomagnesation and β-reductive magnesaethylation of 1-alkenes have been obtained using the DFT method.

Water-Assisted Self-Aggregation of Benzimidazole and Triazole Adducts.

The manuscript revolves around an interesting observation of solidification of a solution of N-((1-((1-ethyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-1,2,3-triazole-4-yl)methyl)aniline (A6) in the NMR tube after around 12 h. Real-time images showed fibrillar and spherulitic growth with tip branching and side branching, which is thermoreversible. The compound under investigation is unique because it is synthesized to understand the anticancer activity with two pharmacophores, benzimidazole and triazole. Click chemistry is employed for in situ generation of triazole moiety on benzimidazole. Previously, benzimidazole-based compounds have shown self-aggregation-induced gel-like behavior because of hydrogen bonding and/or π–π stacking interactions. In the present case, NMR titrations with D2O addition showed two distinct changes in the chemical shift for methylene bridges (connecting benzimidazole and triazole ring) and ortho protons of the phenyl ring (attached to triazole ring). Interestingly, a single-crystal X-ray structure shows the absence of hydrogen bonds and π–π stacking while in the presence of only two distinct close contacts, completely correlating NMR data discussed in detail. A similar “molecular origin” for self-aggregation is observed in seven other flexible but regioisomeric compounds, which were designed and synthesized for inducing hydrogen bonding through the removal of N-ethyl group and insertion of aniline and/or fluoro group.

Spectroscopic differentiation and chromatographic separation of regioisomeric indole aldehydes: Synthetic cannabinoids precursors

The compounds in this study are the six regioisomeric 2-, 3-, 4-, 5-, 6- and 7-formyl indoles and the corresponding six regioisomeric N-n-pentylindole aldehydes. These compounds can serve as precursor chemicals and synthetic intermediates for a number of synthetic cannabinoid drugs. These two sets (the six regioisomeric indole aldehydes as well as the six regioisomeric pentylindole aldehydes) each have identical elemental compositions and differ in the position of attachment of the aldehyde group on the indole ring.The electron ionization mass spectra for the indole aldehydes were essentially identical. However, the vapor phase infrared spectra showed differences in the absorption frequencies for the NH and carbonyl groups based on intramolecular interactions. The associated NH absorption band occurs as low as 3467 cm−1 while the free band is as high as 3517 cm−1. The aldehyde carbonyl band for the indole aldehydes varies from 1713 cm−1 to 1686 cm−1. Substitution of the aldehyde group on the pyrrole ring for the N-n-pentylindole aldehydes yields lower carbonyl absorption bands. The EI mass spectra for the pentylindole aldehydes are identical with little information for differentiation among these six regioisomeric compounds. The six compounds were separated on a capillary column using gas chromatography and the elution order appears to be related to the steric crowding of the indole ring substituents.

GC-MS and GC-IR analysis of regioisomeric cannabinoids related to 1-(5-fluoropentyl)-3-(1-naphthoyl)-indole

The compounds in this study are the regioisomeric 2-, 3-, 4-, 5-, 6- and 7-(1-naphthoyl) substituted 1-(5-fluoropentyl)-indoles and the 3-(1-naphthoyl) substituted isomer in this series is also known as AM-2201. These compounds are structurally similar to JWH-018 except for the additional fluorine at the terminal end of the n-pentyl side-chain. These six regioisomeric compounds have the identical elemental composition (C24H22FNO) and differ in the position of attachment of the 1-napthoyl group on the indole ring. The electron ionization mass spectra showed similar major fragment ions with a molecular radical cation of significant abundance at m/z 359. The six compounds have similar fragment ions at m/z 127 and 155 for the naphthyl and naphthoyl cations. There is a prominent fragment ion at m/z 342 [M−17]+ in the EI-MS of 1-(5-fluoropentyl)-3-, 4-, 5- and 6-(1-naphthoyl)-indoles due to the loss of the hydroxyl group and this ion is most prominent in the 3-(1-naphthoyl) substituted isomer (AM-2201).The six compounds were separated using gas chromatography on a capillary column containing a trifluoropropylmethyl polysiloxane (Rtx-200) stationary phase. The elution order appears to be related to the steric crowding of the indole ring substituents. The 7- and 2-(1-naphthoyl) substituted isomers eluted first due to the possibility for maximum interactions between the naphthyol and alkyl side-chains.The vapor phase infrared spectra differentiate among these six compounds based on the position of the 1-naphthoyl group on the indole ring. The vapor phase spectra for these compounds are compared to the non-fluorinated analogues, JWH-018 and its regioisomeric equivalents.

Prediction of designer drugs: Synthesis and spectroscopic analysis of synthetic cathinone analogs that may appear on the Swedish drug market.

The use of hyphenated analytical techniques in forensic drug screening enables simultaneous identification of a wide range of different compounds. However, the appearance of drug seizures containing new substances, mainly new psychoactive substances (NPS), is steadily increasing. These new and other already known substances often possess structural similarities and consequently they exhibit spectral data with slight differences. This situation has made the criteria that ensure indubitable identification of compounds increasingly important. In this work, 6 new synthetic cathinones that have not yet appeared in any Swedish drug seizures were synthesized. Their chemical structures were similar to those of already known cathinone analogs of which 42 were also included in the study. Hence, a total of 48 synthetic cathinones making up sets of homologous and regioisomeric compounds were used to challenge the capabilities of various analytical techniques commonly applied in forensic drug screening, ie, gas chromatography-mass spectrometry (GC-MS), gas chromatography-Fourier transform infrared spectroscopy (GC-FTIR), nuclear magnetic resonance (NMR), and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Special attention was paid to the capabilities of GC-MS and GC-FTIR to distinguish between the synthetic cathinones and the results showed that neither GC-MS nor GC-FTIR alone can successfully differentiate between all synthetic cathinones. However, the 2 techniques proved to be complementary and their combined use is therefore beneficial. For example, the structural homologs were better differentiated by GC-MS, while GC-FTIR performed better for the regioisomers. Further, new spectroscopic data of the synthesized cathinone analogs is hereby presented for the forensic community. The synthetic work also showed that cathinone reference compounds can be produced in few reaction steps.

Correlation of vapor phase infrared spectra and regioisomeric structure in synthetic cannabinoids

The twelve 1-n-pentyl-2-, 3-, 4-, 5-, 6- and 7-(1- and 2-naphthoyl)-indoles each have the same substituents attached to the indole ring, identical elemental composition (C24H23NO) yielding identical nominal and accurate masses. These twelve isomers cover all possible positions of carbonyl bridge substitution for both indole (positons 2–7) and naphthalene rings (positions 1 and 2). Regioisomeric compounds can represent significant challenges for mass based analytical methods however, infrared spectroscopy is a powerful tool for the identification of positional isomers in organic compounds. The vapor phase infrared spectra of these twelve uniquely similar compounds were evaluated in GC-IR experiments. These spectra show the bridge position on the indole ring is a dominating influence over the carbonyl absorption frequency observed for these compounds. Substitution on the pyrrole moiety of the indole ring yields the lowest CO frequency values for position 2 and 3 giving a narrow range from 1656 to 1654cm−1. Carbonyl absorption frequencies are higher when the naphthoyl group is attached to the benzene portion of the indole ring yielding absorption values from 1674 to 1671cm−1.The aliphatic stretching bands in the 2900cm−1 region yield a consistent triplet pattern because the N-alkyl substituent tail group remains unchanged for all twelve regioisomers. The asymmetric CH2 stretch is the most intense of these three bands. Changes in positional bonding for both the indole and naphthalene ring systems results in unique patterns within the 700 wavenumber out-of-plane region and these absorption bands are different for all 12 regioisomers.

Differentiation of methylated indole ring regioisomers of JWH-007: GC–MS and GC–IR studies

The five regioisomeric methylated indole ring analogues of JWH-018 can be prepared directly from a common set of precursor materials. These five isomers include 2-methyl-1-n-pentyl-3-(1-naphthoyl)-indole (JWH-007) and its four regioisomeric analogues, 4-, 5-, 6- and 7-methyl substituted indoles. The EI-MS spectra show equivalent regioisomeric major fragments resulting from cleavage of the groups attached to the central indole nucleus. The characteristic [M−17]+ fragment ion at m/z 338 resulting from the loss of OH group is significant in the mass spectra of all the studied compounds except Compound 2 (JWH-007) which has two significant fragment ions at m/z 340 and m/z 270. Cations at m/z 298, 284, 228 and 200 result from fragmentation of the naphthoyl and/or n-pentyl groups. GC separations on a trifluoropropylmethyl polysiloxane (Rtx-200) provided excellent resolution of these compounds. The elution order appears to be related to the degree of crowding of indole ring substituents. The vapor phase infrared spectra in the range of 1700–700 cm−1 showed unique and characteristic absorption patterns for each of the five regioisomeric compounds which allowed for discrimination among the isomers in this set of cannabinoid compounds.

Facile Separation of Regioisomeric Compounds by a Heteronuclear Organometallic Capsule.

Owing to the often-similar physical and chemical properties of structural isomers of organic molecules, large efforts have been made to develop efficient strategies to isolate specific isomers. However, facile separation of regioisomeric compounds remains difficult. Here we demonstrate a universal organometallic capsule in which two silver centers are rigidly separated from each other by two tetranuclear [Rh4] pyramidal frustums, which selectively encapsulate a specific isomer from mixtures. Not only is the present heterometallic capsule suitable as a host for the encapsulation of a series of aromatic compounds, but also the receptor shows widely differing specificity for the various isomers. Direct experimental evidence is provided for the selective encapsulation of a series of para (p)-disubstituted benzene derivatives, such as p-xylene, p-dichlorobenzene, p-dibromobenzene, and p-diiodobenzene. The size and shape matching, as well as the Ag-π interactions, are the main forces governing the extent of molecular recognition. The encapsulated guest p-xylene can be released by using the solid-liquid solvent washing strategy, and the other guest molecules are easily liberated by using light stimulus.

GC–MS differentiation of the six regioisomeric dimethoxybenzoyl-1-pentylindoles: Isomeric cannabinoid substances

The six regioisomeric 1-pentyl-3-dimethoxybenzoylindoles can be differentiated by a combination of EI-MS and FT-IR spectra. The six regioisomeric 1-n-pentyl-3-(dimethoxybenzoyl)-indoles represent potential designer modifications in the synthetic cannabinoid drug category. The analytical properties and methods of regioisomeric differentiation were developed in this study. The base peaks in these six spectra allow these compounds to be subdivided into three groups of two compounds each, the m/z 334 ion is the base peak for the 2,4- and 2,6-dimethoxybenzoyl isomers (compounds 2 and 4), the 2,3- and 2,5-dimethoxybenzoylindole isomers (compounds 1 and 3) show the m/z 200 ion of base peak intensity and the 3,4- and 3,5-isomers (compounds 5 and 6) show the molecular ion as the base peak, m/z 351. The four isomers having a methoxy group substituted at the ortho position show a unique fragment ion occurring at [M-17]+. An interesting fragment ion at m/z 200 is significant in the 2,3 and 2,5 isomers and completely absent in the 3,4 and 3,5 isomers. Minor peaks for m/z 200 appear in the mass spectra of the 2,4 and 2,6-isomers.This set of regioisomeric compounds was well resolved by capillary gas chromatography on a dimethylpolysiloxane stationary phase. The elution order appears related to the degree of substituent crowding in the dimethoxybenzoyl group. FTIR spectra provide useful data for differentiation among these regioisomeric compounds. Infrared absorption spectral data provide distinguishing and characteristic information to individualize the regioisomers in this set of compounds.

Synthesis and Characterization of <sup>13</sup>C-labeled Alkenyl Succinic Anhydride (ASA) with Defined Double Bond Location

Alkenyl succinic anhydride (ASA) is one of the most prominent paper sizing agents worldwide. Commercial products start from isomerized C16-18 olefins with certain distribution of the double bond along the alkyl chain. This distribution is then found again in the product ASA which renders mechanistic studies on ASA binding to the cellulose surface difficult. For studies on ASA reactivity, olefins with defined double bond location (2-, 4-, 6-octadecene and 6-icosene) were synthesized according to Wittig protocols, and further reacted with 13C-labeled maleic anhydride to give ASA model compounds with defined double bond location and 13C-labeled carbonyl group. The olefinic products of the Wittig synthesis, rich in cis-isomers, afforded exclusively trans-configured compounds upon the enereaction with maleic anhydride. The reactions afforded four products, two regioisomeric compounds with different position of the double bond, each of which as threo- and erythro-isomer in different ratios. The products were comprehensively analytically characterized including a full NMR resonance assignment in the 1H and 13C domain. The model compounds are now used in combination with gel and solid-state NMR for studies on ASA reactivity towards cellulosic surfaces with a focus on the questions whether - and to what extent - covalent binding of ASA to cellulose can occur under conditions relevant to paper production and paper sizing. Keywords: Alkenyl succinic anhydride (ASA), attenuated total reflection infrared (ATR-IR) spectroscopy, ene reaction, isotopic labeling, nuclear magnetic resonance (NMR) spectroscopy, paper sizing, Wittig reaction.

A Novel and Highly Regioselective Synthesis of New Carbamoylcarboxylic Acids from Dianhydrides

A regioselective synthesis has been developed for the preparation of a series of N,N′-disubstituted 4,4′-carbonylbis(carbamoylbenzoic) acids and N,N′-disubstituted bis(carbamoyl) terephthalic acids by treatment of 3,3′,4,4′-benzophenonetetracarboxylic dianhydride (1) and 1,2,4,5-benzenetetracarboxylic dianhydride (2) with arylalkyl primary amines (A-N). The carbamoylcarboxylic acid derivatives were synthesized with good yield and high purity. The specific reaction conditions were established to obtain carbamoyl and carboxylic acid functionalities over the thermodynamically most favored imide group. Products derived from both anhydrides 1 and 2 were isolated as pure regioisomeric compounds under innovative experimental conditions. The chemo- and regioselectivity of products derived from dianhydrides were determined by NMR spectroscopy and confirmed by density functional theory (DFT). All products were characterized by NMR, FTIR, and MS.

GC–MS and GC-IRD studies on the six ring regioisomeric dimethoxybenzoylpiperazines (DMBzPs)

The dimethoxybenzoylpiperazines show mass spectra characteristic for this set of six regioisomeric substances and the position of ring substitution for the dimethoxy groups can be determined by vapor phase infrared methods. The dimethoxybenzoylpiperazines are characterized by several fragment ions unique to the mass spectra for this set of regioisomeric compounds. Ions at m/z 165 and 182 indicate the presence of the dimethoxybenzoyl and dimethoxybenzamide groups while low mass ions at m/z 56, 69 and 85 are characteristic of the piperazine ring in these isomeric compounds. The mass spectra for these regioisomeric dimethoxybenzoylpiperazines are almost identical and this method alone does not provide for the confirmation of identity of any one of the isomers to the exclusion of the other compounds.The perfluoroacyl derivatives of the six regioisomers were resolved by gas chromatography and their mass spectra showed some differences in relative abundance of fragment ions without the appearance of any unique fragments for specific confirmation of structure. Gas chromatography with infrared detection (GC-IRD) provides direct confirmatory data for the differentiation between the regioisomeric underivatized dimethoxybenzoylpiperazines.

Evaluation of Anti-nociceptive and Anti-inflammatory Activities of Novel Chalcone Derivatives.

Chalcone (1,3-diarylprop-2-en-1-one) derivatives have been introduced as selective cyclooxygenase-2 inhibitors. In the present study, anti-nociceptive and anti-inflammatory effects of eight novel compounds were evaluated in male mice and Wistar rats by using the writhing and formalin-induced paw edema tests respectively. The activities of the compounds were compared with celecoxib as a reference drug. Then, novel compounds were divided into two regioisomeric groups based on the position of the methylsulfonyl substitution. Compounds with substituents such as: 1) H, 2) Me, 3) F and 4) Cl at para position of the phenyl ring of (E)-3-(4-Methanesulfonylphenyl)-1-phenylprop-2 en-1-one were selected in the first group. The regioisomer compounds with 5) H, 6) Me, 7) F and 8) OMe substitutions at C-4 of phenyl ring of (E)-1-(4-Methanesulfonylphenyl)-3-phenylprop-2-en-1-one were chosen as second group. All compounds showed dose-dependent anti-nociceptive activity in writhing test. Interestingly, the potency of anti-nociceptive effect of compounds 1, 2, 5 and 6 were significantly higher than celecoxib. The regioisomeric compounds 1 and 5 with high anti-nociceptive effects, showed a significant dose-dependent anti inflammatory activity in the paw edema test as well. The results showed that compounds with no substituent or small size substituents at para position of the phenyl ring are the most potent compound in writhing test. Our results revealed that the introduction of a bulky group such as methoxy or chlorine at the vicinal aromatic chain of the derivatives decreases the anti-inflammatory/ anti-nociceptive effects. The comparison of estimated ED50 of each pair of the regioisomeric compounds indicates that the relative position of SO2Me to carbonyl moiety did not affect the potency.

Diverse Directions of Heterocyclizations Involving Derivatives of 5-Aminopyrazoles and N-Arylmaleimides

Heterocyclization reactions between derivatives of 5-aminopyrazoles and N-arylmaleimides were studied and it was established that several directions are possible. Cyclizations involving 1,3-unsubstituted 5-aminopyrazoles yielded mixtures of two regio-isomeric compounds, pyrazolo[1,5-a]pyrimidine-7-carboxamides and pyrazolo[3,4-b]pyridine-4-carboxamides. Reactions of 4-substituted 5-aminopyrazoles in boiling acetic acid or N,N-dimethyl-formamide in most cases gave pyrazolo[1,5-a]pyrimidine-7-carboxamides as the sole product. The treatment of 1-substituted 5-aminopyrazoles with maleimides possesses high selectivity only in N,N-dimethylformamide yielding pyrazolopyridines while in acetic acid the formation mixtures with pyrrolopyrazolones is observed. The key intermediates of the reaction studied were isolated and discussed.