A comparative study of conventional conditions versus microwave irradiation for the preparation of novel 1,2‐dihydro‐2‐imino‐7‐methyl‐1,6(6H)‐naphthyridin‐5‐ones

The synthesis of novel 1,6‐naphthyridines 6 with potential activity against tuberculosis is described using the reaction sequence 2←4←6. Depending on the ring N‐substitution of the 4‐alkylamino‐6‐methyl‐2(1H)‐pyridones 1 and 2 the electrophilic attack of the Vilsmeier reagent gives rise to the formation of the exocyclic N‐formyl derivatives 3 from 1 and the corresponding 3‐carbaldehydes 4 from 2. 1,2‐Dihydro‐2‐imino‐7‐methyl‐1,6(6H)‐naphthyridin‐5‐ones 6a‐j are prepared by the Knoevenagel reaction of 4 with CH‐acidic nitriles 5. These reactions are carried out using a comparative study of conventional conditions (room temperature or reflux) versus microwave irradiation.     

Differential response of terpenes and anthraquinones derivatives in Rumex dentatus and Lavandula officinalis to harsh winters across north-western Himalaya

Herbs adapted to diverse climates exhibit distinct variability to fluctuating temperatures and demonstrate various metabolic and physiological adaptations to harsh environments. In this research, Rumex dentatus L. and Lavandula officinalis L. were collected before snowfall in September–November to evaluate variability in major phytoconstituents to diverse seasonal regime. LC-MS was used for simultaneous determination of eight anthraquinone derivatives in R. dentatus, i.e. emodin, physcion, chrysophanol, physcion glucoside, endocrocin, emodin glucoside, chrysophanol glucoside and chromone derivatives and monoterpenes in L. officinalis i.e. (Z)-β-ocimene, (E)-β-ocimene, terpene alcohol, terpin-4-ol, acetate ester-linalyl acetate and bicyclic sesquiterpene (E)-caryophyllene. The correlation analysis confirmed significant variation in anthraquinone glucoside and terpene content within Rumex and Lavender, respectively, and altitude was established as the determinant factor in secondary metabolism of both herbs. The study concludes the propagation of herbs in bioclimatic belts which favour accumulation of major constituents and validate their greater pharmacological activity.     

On the Reaction of Some Saccharin Derivatives with Hydrazine and Other Nucleophils

 The reaction of methyl saccharin-2-acetate with hydrazine gave no 3-hydrazino derivative of saccharin as reported in literature, but yielded with ring opening the benzohydrazide derivative. The analogue reaction was observed when saccharin-2-(2-propionate) was reacted with hydrazine. Furthermore, using an excess of hydrazine, the ester group was transformed into the carbohydrazide too. All hydrazides were fully characterized as hydrazones by reactions with different ketones. The 3-thioxo compounds were prepared by reactions with P₂s₅, but the yield was improved by using Lawesson’s reagent. No attack at the ester group was observed. Finally, reactions of the saccharin-2-carboxylate with some amino acids gave substituted benzamides by attack at position 3 and ring opening. In none of the reactions of the saccharin derivatives with nitrogen nucleophiles a formal substitution of the 3-oxo group was observed.     

Mass spectral study of ring E of taraxasterol and compounds with similar ring substitution

The origin of the [M–69]⁺ and [M–111]⁺ signals in the mass spectrum of taraxasterol was studied through the use of C(18), (19), (21), (22) and/or (30) deuteriated derivatives. The generality of these signals for ring systems with an exocyclic methylene group and a methyl moiety on an adjacent carbon was verified with 2-methylmethylenecyclohexane, 1-methyl-2-methylene-trans-decalin, 1,10-dimethyl-2-methylene-trans-decalin and some of their deuteriated derivatives. The most plausible mechanism for the formation of the [M–69]⁺ ion appears to involve cleavage of both bonds allylic to the exocyclic methylene group with a 1,3-hydrogen transfer from the adjacent ring. Genesis of the [M–111]⁺ ion is more complicated but a five-membered allylic ion generated from ring D is proposed.     

Synthesis of purpurin-18 imide derivatives from chlorophyll-a and -b by modifications and functionalizations along their peripheries

The methyl pheophorbide-a and methyl pheophorbide-b were used as starting materials and converted to purpurin-18 ester by ring-opening and rearrangement reaction in their exocyclic ring. N-Substituted purpurin-18 imides were obtained from purpurin-18 ester through amidation reaction of six-membered cyclic anhydride. Further chemical modifications along their peripheries were carried out by a variety of common reactions, including electrophilic substitution, Wittig reaction, allomerization and Vilsmeier reaction, to afford the title compounds with long-wavelength absorption. The structures of all new chlorins were characterized by elemental analysis, IR, UV–vis and ¹H NMR spectra.     

An unusual labilization of a 4-(trifluoromethyl)thiazole

N-Chloro-4-(trifluoromethyl)-5-thiazolyl-N',N'-diethylurea 5 has been found to undergo a facile labilization of the trifluoromethyl group under mild conditions. The reaction relies on the assistance of the nitrogen substitution at the 4-position of the thiazole ring. Treatment of 5 with triethylamine and either methanol or methanethiol replaced the trifluoromethyl group with a methyl ester or a trimethylorthothio ester respectively at room temperature. Combination of 5 with diethylamine led to an unusual thiazolidine with two exocyclic double bonds, 8 .     

Synthesis and antibacterial activity of emodin and its derivatives against methicillin-resistant Staphylococcus aureus

Synthesis of the antibacterial emodin was improved using Friedel-Crafts acylation as a key step leading to 37% overall yield. In addition, 21 analogues were synthesized by structural modification of the hydroxyl and methyl groups, as well as the aromatic ring of emodin. Antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and cytotoxicity against noncancerous Vero cells were evaluated. A structure-activity relationship (SAR) study indicated that the hydroxyl groups and the methyl group in the emodin skeleton were crucial for anti-MRSA activity. Furthermore, the presence of an iodine atom or ethylamino group on the aromatic ring enhanced the anti-MRSA activity with higher selectivity indices, while derivatives containing bromine, chlorine atoms or quaternary ammonium salt were as active as emodin. The quaternary ammonium group on the aromatic ring also led to non-cytotoxicity against Vero cells.     

On the Reaction of Some Saccharin Derivatives with Hydrazine and Other Nucleophils

Summary.  The reaction of methyl saccharin-2-acetate with hydrazine gave no 3-hydrazino derivative of saccharin as reported in literature, but yielded with ring opening the benzohydrazide derivative. The analogue reaction was observed when saccharin-2-(2-propionate) was reacted with hydrazine. Furthermore, using an excess of hydrazine, the ester group was transformed into the carbohydrazide too. All hydrazides were fully characterized as hydrazones by reactions with different ketones. The 3-thioxo compounds were prepared by reactions with P₂s₅, but the yield was improved by using Lawesson’s reagent. No attack at the ester group was observed. Finally, reactions of the saccharin-2-carboxylate with some amino acids gave substituted benzamides by attack at position 3 and ring opening. In none of the reactions of the saccharin derivatives with nitrogen nucleophiles a formal substitution of the 3-oxo group was observed. Corresponding author. E-mail: ottohh@pharmazie.uni-greifswald.de Received July 4, 2002; accepted August 1, 2002 Published online February 20, 2003     

Study on the Methyl Migration of 10-Methoxy-5,10-dihydrophenophosphazine 10-oxide

The title compound (1) was treated with NaH at room temperature in anhydrous DMF to give a sodium salt (containing nitrogen anion)which could shift the methyl group from oxygen to nitrogen atom to form N-methyl phosphinic acid as the reaction temperature was increased to 120 ℃.Three nitro derivatives containing 5,10-dihydrophenophosphazine ring system were prepared for the investigation on the above reaction mechanism which would be possible regarded as a special inter-molecular substitution.viz.,the nucleophilic nitrogen anion from one molecule of 1 attacked the cabon atom of the O-methyl of another 1.In addition,the chemical structures of seven compounds containing 5,10-dihydrophenophosphazine ring system involved in the experiment were confirmed by IR,^1 H NMR,^31P NMR and mass spectroscopy.     

Amide acetals in the synthesis of pyridothienopyrimidines

Methyl 3-amino-4-arylaminothieno[2,3-b]pyridine-2-carboxylates containing various substituents in the benzene ring were synthesized by the Thorpe-Ziegler reaction of 4-arylamino-2-chloropyridine-3-carbonitriles with methyl thioglycolates. The influence of the substituent in the benzene ring, acetal structure, the solvent and the process temperature on the reactions of obtained compounds with amide acetals was studied. It was established that reactions with dimethylacetamide dimethylacetal in toluene smoothly results in amidine derivatives, viz., methyl 4-arylamino-3-[1-(dimethylamino)ethylidene]aminothieno[2,3-b]pyridine-2-carboxylates, regardless of the substituent in the benzene ring. Analogous reaction of p-fluoroderivative with dimethylacetamide dimethylacetal in refluxing anhydrous ethanol leads to intramolecular cyclocondensation to produce substituted pyridothienopyrimidines, viz., 5H-1-thia-3,5,8-triazaacenaphthenes, in good yields. Amidine derivatives were the major products in the case of the coupling of aminothienopyridines with dimethylformamide dimethylacetal under the same conditions. A new approach to the synthesis of substituted pyridothienopyrimidines, viz., 3H-1-thia-3,5,8-triazaacenaphthylenes, based on the prolonged heating of methyl 4-arylamino-3-[1-(dimethylamino)ethylidene]aminothieno[2,3-b]pyridine-2-carboxylates in the excess of acetic anhydride was elaborated. Putative mechanisms of the processes concerned are given.     

High-performance thin layer chromatography method for quantitative determination of four major anthraquinone derivatives in Rheum emodi

A high-performance thin layer chromatographic (HPTLC) method for the rapid and simple quantification of the four major anthraquinone derivatives i.e. physcion, chrysophanol, emodin and chrysophanol glycoside in Rheum emodi is described. HPTLC of anthraquinone derivatives was performed on pre-coated RP-18 F254S HPTLC plates. For achieving good separation, the mobile phase of methanol-water-formic acid (80:19:1, v/v/v) was used. The densitometric determination of anthraquinone derivatives was carried out at 445 nm in reflection/absorption mode. The calibration curves were linear in the range of 20-100 ng for physcion, 80-400 ng for chrysophanol and emodin, and 200-1000 ng for chrysophanol glycoside. The method was found to be reproducible and convenient for quantitative analysis of anthraquinone derivatives in the methanolic extract of rhizomes of R. emodi collected from three different locations of Western Himalaya, India.     

Condensation of isophorone and isophorone oxime with amines and aldehydes

Mannich condensations of isophorone (3,5,5-trimethylcyclohex-2-en-1-one) with paraformaldehyde and dimethylamine, benzylamine, and piperidine hydrochlorides were studied. The reactions were not selective, and they involved both activated methylene group and vinylic carbon atom, as well the exocyclic methyl group at the double bond. The corresponding isomeric amino ketones were formed in comparable amounts (42, 30, and 28%). The E and Z isomers of isophorone oxime reacted with paraformaldehyde and dimethylamine hydrochlride to give mixtures of analogous Mannich condensation products, but the fraction of the addition product at the carbon atom spatially close to the oxime hydroxy group was larger. Under analogous conditions, the reaction of isophorone with aromatic amines and aromatic aldehydes gave products of two-component condensation of isophorone with aldehydes, and the reactions involved exclusively the activated methylene group in the initial enone with formation of the corresponding trans,trans-isomeric 7-arylmethylidene derivatives.     

New 1,2,3‐triazolo[4,5‐d]1,2,4‐triazolo[3,4‐b]pyridazine derivatives II

New tricyclic 1,2,3‐triazolo‐1,2,4‐triazolo‐pyridazine derivatives, bearing a methyl substituent on the 1,2,3‐triazole ring, were prepared as potential biological agents. N‐Methylation of dimethyl 1,2,3‐triazole‐4,5‐dicarboxylate allowed synthesis of the isomeric 1‐methyl‐4,7‐dihydroxy and 2‐methyl‐4,7‐dihydroxy triazolo‐pyridazines 4a and 4b which, by a chlorination reaction, gave the corresponding 1‐methyl‐4‐chloro‐( 6a ), 1‐methyl‐7‐chloro‐ ( 6b ) and 2‐methyl‐4‐chloro‐ ( 9 ) substituted 1,2,3‐triazolo‐pyridazines. The nucle‐ophilic substitution with hydrazine hydrate and the suitable cyclization to form the 1,2,4‐triazole ring, provided the expected tricyclic isomeric derivatives 8a, 8b and 11 respectively. The p‐methoxybenzyl substituent, introduced as a leaving group to obtain either v‐triazolo‐pyridazine or v‐triazolo‐s‐triazolo‐pyri‐dazine derivatives unsubstituted on the 1,2,3‐triazole ring, appeared inadequate. Some compounds underwent binding assays toward the adenosine A₁and A_2A receptors.     

Isolation and identification of anthraquinones of Caloplaca cerina and Cassia tora

Five hydroxyanthraquinone derivatives physcion, emodin, fallacinal, teloschistin, and 1,3-dimethoxy-8-hydroxy-6-methyl-9,10-anthraquinone were isolated from the lichen Caloplaca cerina growing in Serbia. Three anthraquinone derivatives, namely physcion, emodin, and rhein were isolated and identified from the Thai medicinal plant Cassia tora. Presented at the 33rd International Conference of the Slovak Society of Chemical Engineering, Tatranské Matliare, 22–26 May 2006.     

An Efficient Route to Emodic Amine and Analogous O-Methyl Protected Derivatives Starting from Emodin

Emodic amine could be synthesized in a five-step approach in excellent overall yield by following a modified Curtius rearrangement strategy, starting from the naturally occurring emodin. This unique emodin derived 6-amino substituted polyhydroxylated anthraquinone may serve as a promising synthon for a new class of amino functionalized photodynamically active hypericin derivatives. In addition, the partially O-methyl protected 6-amino- and 6-carboxy-anthraquinones could be synthesized in high yields via selective O-methyl ether cleavage from the corresponding tri-O-methyl derivatives.     

NMR Characterization of Substituted Aromatic Poly (Ether Sulofone)s

Abstract

The synthesis of a variety of substituted bisphenol A polysulfones, including nitro, amino, aminomethyl, ethyl, and methyl derivatives, is described. Nuclear magnetic resonance (NMR) (both proton and carbon, and several 2-D experiments) data confirm conclusions on the substitution site based on arguments on inductive effects in the phenyl rings. The proton ortho to the oxygen in the bisphenol A (BPA) residue is replaced in electrophilic substitution reactions. The degree of substitution was also calculated from the NMR results. The ethyl and methyl derivatives were expected, from the starting reactants, to each have a BPA ring substituted. The NMR data showed that, on the average, this is true. The nitro derivative also has substitution in every BPA ring, while the amino and aminomethyl derivatives have only intermittent BPA rings substituted. Measured degrees of substitution (DS) varied from 0.11 to 2.25.     

An Efficient Route to Emodic Amine and Analogous <Emphasis Type="Italic">O</Emphasis>-Methyl Protected Derivatives Starting from Emodin

Summary. Emodic amine could be synthesized in a five-step approach in excellent overall yield by following a modified Curtius rearrangement strategy, starting from the naturally occurring emodin. This unique emodin derived 6-amino substituted polyhydroxylated anthraquinone may serve as a promising synthon for a new class of amino functionalized photodynamically active hypericin derivatives. In addition, the partially O-methyl protected 6-amino- and 6-carboxy-anthraquinones could be synthesized in high yields via selective O-methyl ether cleavage from the corresponding tri-O-methyl derivatives.     

Synthesis of the Naphthalenone,Dihydroquinoline, and Dihydrofuran Derivatives

The reactions of enaminones with dimethyl diazomalonate were investigated in the presence of copper(II) acetylacetonate. From the reaction of (E)‐3‐[methyl(phenyl)amino]‐1‐phenylprop‐2‐en‐1‐one ( 6c ), dimethyl 2‐[methyl(phenyl)amino]‐4‐oxonaphthalene‐1,1‐(4H)‐dicarboxylate, was unexpectedly obtained as the major product. Quinoline derivatives were formed as the major products in the case of N‐methyl‐p‐anisidino and N‐methyl‐p‐toluidino enaminones. The reactions of acetyl enaminones were also realized, and quinoline derivatives were isolated as the major products. 3H‐ and 5H‐dihydrofurans were also formed as side products in these reactions. These results differ from those reported earlier on the reactions of tertiary enaminones with carbenes/metal carbenes.     

Effect of the Structure of 1- and 3-Methylpyrimidin-4-ones on the Rate of Nucleophilic Substitution of the 2-Methylsylfanyl Group

Rate constants for substitution of the 2-methylsulfanyl group in 1- and 3-methyl-2-methylsulfanyl-pyrimidin-4-ones and their 5-fluoro analogs were measured in the reaction with butylamine, alkaline hydrolysis, and methanolysis. The rate of substitution in 1-methyl isomers having a zwitterionic structure is greater by a factor of ~2 than the rate of substitution in 3-methyl isomers with conjugated double bonds in the ring. The presence of a fluorine atom in position 5 accelerates nucleophilic substitution in 1-methyl isomers, while 5-fluoro-3-methyl-2-methylsulfanylpyrimidin-4-ones react at a lower rate than their 5-unsubstituted analogs. According to the NMR data, the reactions involve formation of a tetrahedral intermediate. Anchimeric effect of the methyl group on N¹ hampersattack by basic reagent on the C⁶atom.     

Kinetics and products of the reactions of ozone with toluene and its derivatives in acetic anhydride

The reactions of ozone with toluene and its derivatives in acetic anhydride were studied. It was found that competing parallel reactions of ozone with the aromatic ring and substituents occurred in the ozone-arene-acetic anhydride system. The ratio between these reaction paths depended on the arene structure and reaction conditions. The selectivity of the oxidation of toluene and its derivatives at the methyl group varied from 0 to 40%. The fraction of aromatic products decreased as the number of methyl groups at the ring was increased. Tri- and tetramethylbenzenes were oxidized only at the aromatic ring. The stability of an aromatic system increased upon the introduction of electron-acceptor substituents into the benzene ring. Aminotoluenes and hydroxytoluenes were oxidized with ozone mainly at the NH₂ and HO groups; however, as in the case of toluene, the aromatic ring and methyl group became the main directions upon their acylation. The oxidation of the methyl group in acetic anhydride in the presence of sulfuric acid was finished at the step of the formation of the acylated derivatives of benzyl alcohols and benzaldehydes, which are resistant to the action of ozone.