New heteroaromatic compounds—XIII Reactions of 10-substituted 9-ethoxycarbonyl-10:9-Borazarophenanthrenes

10-Ethoxycarbonyl derivatives of 10:9-borazarophenanthrenes have been prepared by reaction of the 10-lithio derivatives with ethyl chloroformate. Unlike the parent compounds they are rapidly oxidized by air to products in which the BN bond is broken. These reactions suggest that the stability of the present compounds to oxidation and hydrolysis must be due to resonance stabilization. A measurement of the dipole moment of 10-methyl-10:9-borazarophenanthrene by Professor R. Huisgen and his collaborators is reported.     

Synthesis and Diazotization of Diethyl 6-Amino-2-Hydroxyazulene-1,3-Dicarboxylate and Its 2-Acetoxyl Derivative

Diethyl 6-amino-2-hydroxyazulene-1,3-dicarboxylate ( 6a ) and 2-acetoxyl derivative ( 6b ) were synthesized by reduction of the 6-azido derivatives ( 5a,b ) with zinc/acetic acid in excellent yields. 5a and 5b were prepared by azidation of diethyl 2-acetoxy-6-bromoazulene-1,3-dicarboxylate (4). Diazotization of 6a with sodium nitrite in the presence of concentrated sulfuric acid in dioxane gave diethyl 2-hydroxy- ( 7a ), 2,6-dihydroxy- ( 8a ), and 2-hydroxy-6-[2-(2-hydroxyethoxy)ethoxy]-azulene-1,3-dicarboxylates ( 9a ), in 5, 35 and 20% yields, respectively. Similar reaction of 6b gave the corresponding acetates 7b, 8b , and 9b , compounds of the same type from 6a . No evidence for the formation of 6-diazo-1,3-diethoxycarbonyl-2(6H) azulenone ( 2b ) was obtained in the employed reaction conditions.     

Synthesis and electrophilic substitutions of novel pyrazolo[1,5-c]-1,2,4-triazolo[4,3-a]pyrimidines

5-Aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimidines 1 were used as precursors for the preparation of a new series of 5-aryl-8-phenylpyrazolo[1,5-c]-1,2,4- triazolo[4,3-a]pyrimidines 2. The reactions of 2 with certain electrophilic reagents gave the respective 6-substituted derivatives 3-5 rather than the 7-isomeric products. Formylation of the key compounds 1 with ethyl formate yielded the formyl derivatives 6. Furthermore, boiling of compounds 1 with acetic acid afforded 7-acetylhydrazino-5-aryl-2-phenylpyrazolo[1,5-c]pyrimidines 7. Bromination of 7 yielded the dibromo- derivatives 8, while their iodination and nitration gave the monosubstituted derivatives 9 and 10, respectively. Also, treatment of 1 with boiling acetic anhydride yielded the triacetyl derivatives 11. The structure of synthesized products was confirmed by elemental analyses, IR, 1H NMR and MS spectra.     

Synthesis of 3-Hydroxy-6-Methyl- and 3-Hydroxy-2-(2-phenylethyl)pyridines and Their Sulfur-Containing Amino and Hydroxymethyl Derivatives

The aminomethylation of 3-hydroxy-6-methyl- and 3-hydroxy-2-(2-phenylethyl)pyridines by secondary amines has been investigated. It was shown that like 2-alkyl-3-hydroxypyridine aminomethylation is directed primarily to position 6 and then 4 of the pyridine ring. On heating the aminomethyl derivatives of 3-hydroxy-6-methyl- and 3-hydroxy-2-(2-phenylethyl)pyridines with acetic anhydride the corresponding acetoxy derivatives were obtained, which were converted on heating with hydrochloric or hydrobromic acids into hydroxy and bromomethyl derivatives. Isothioureidomethyl and benzimidazolylthiomethyl derivatives were synthesized by heating the bromomethyl-substituted derivative with thiourea or with 2-mercaptobenzimidazole. The structures of compounds were confirmed by data of ¹H NMR spectra. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1189–1194, August, 2005.     

Synthetic analogues of Peganum alkaloids. III. Pentamethylenequinazolones

Monosubstituted 5-, 6-, and 8-methoxy-3,4-dihydro-2,3-pentamethylenequinazolones (1–3) have been syntehsized by the condensation of monosubstituted methoxyanthranilic acids with caprolactam. Demethylation with hydrobromic acid gave the corresponding hydroxy compounds [4–6]. When the 6- and 8-methoxy- and 6- and 8-hydroxy-3,4-dihydro-2,3-pentamethylenequinazolones (2, 3, 5, and 6) were reduced with zinc in hydrochloric acid, the corresponding quinazoline derivatives (7–10) were obtained. The melting points of the basis and their hydrochlorides are given. Some features of their UV, mass, and PMR spectra are reported.     

1,4,4a,10b-Tetrahydro-N,N-dimethyl-4-phenanthridinamines and 1,4,4a,5,6,10b-hexahydro-N,N-dimethyl-4-phenanthridinamines

Synthetic procedures to prepare the title compounds are described. Diels-Alder cycloaddition of β-nitrostyrene derivatives 5 to N,N-dimethyl-1,3-butadien-1-amine, 6 , gave 5-aryl-N,N-dimethyl-6-nitro-2-cyclohexen-1-amines 7. Reduction of 7 with zinc in acetic acid gave the diamino derivatives 8 . Schotten-Baumann acylation of 8 gave amides 9 . Treatment of 8 with alkyl isocyanates gave the aminourea derivatives 10 . Bischler-Napieralski cyclodehydration procudure of 9 and 10 gave 1,4,4a,10b-tetrahydrophenanthridinamines 3 and N⁶-alkyl-1,4,4a,10b-tetrahydro-N⁴,N⁴-dimethyl-4,6-phenanthridinediamines 11 , respectively. Condensation of diamines 8 with aryl aldehydes under azeotropic conditions gave imines 12 which on treatment with acids yielded 6-aryl-1,4,4a,5,6,10b-hexahydro-N,N-dimethyl-4-phenanthridinamines 4 . The stereochemistry of these materials is assigned from the proton magnetic resonance studies.     

Synthesis of some azo compounds and a study of their properties

11 azo compounds hitherto undescribed in the literature are synthesized. The azo components used were 8-hydroxyquinoline, resorcinol, pyrogallol, and 7-iodo-8-hydroxy-5-quinolinesulfonic acid, while the diazol components were sulfanilamide and a number of its derivatives. The acid dissociation constants for 8 azo compounds are determined by a solubility method and also spectrophotometrically. The constants are of the order 10^?7-10^?9.     

Synthesis and Reactions of Some Novel Nicotinonitrile,Thiazolotriazole, and Imidazolotriazole Derivatives for Antioxidant Evaluation

The novel 2-(1H)-pyridone, the lead compound of the pyridone derivative 1, reacted with an electrophilic reagent (ethyl chloroacetate) to give the corresponding ester 2. Condensation of compound 2 with thiosemicarbazide and/or hydrazine hydrate afforded the mercaptotriazole and the corresponding acetic acid hydrazide derivatives 3 and 4, respectively. The latter compound reacted with ethyl acetoacetate, ethyl cyanoacetate, and maleic anhydride to give compounds 5, 6, and 7, respectively. Alkylation of compound 3 with methyl iodide or chloroacetic acid afforded methylsulfanyltriazole and thiazolotriazole derivatives 8 and 9, respectively. Compound 8 reacted with glycine to afford the imidazotriazole derivative 10. Both compounds 9 and 10 reacted with glucose and benzaldehyde to give compounds 11, 12, 13, and 14, respectively. Some of the prepared products were selected and subjected to screening for their antioxidant activity.     

Synthesis of (-)-11 Hydroxy-delta8-6a, 10a-trans-tetrahydrocannabinol

When (?)-Δ⁸-6a, 10a-trans-THC (THC = Tetrahydrocannabinol), in the form of its diacetate, was irradiated in the presence of oxygen and a sensitizer, followed by reduction with NaBH₄, three allylic alcohols were formed: (?)-8α-and (?)-8β-hydroxy-Δ^9,11-THC (proportion 3:1) and (?)-9α-hydroxy-Δ^7,8-THC. Acetylation of the epimeric 8-hydroxy-compounds with Ac₂O/pyridine gave the corresponding diacetates. When (?)-Δ⁸-6a, 10a-trans-THC, in the form of its tetrahydropyranyl derivative, was heated with m-chloroperbenzoic acid, the two epimeric 8,9-epoxides were formed in equal amounts. These compounds, on treatment with butyllithium, afforded (?)-8α- and (?)-8β-hydroxy-Δ^9,11- 6a, 10a-trans-THC-tetrahydropyranylether. After removing the protecting group and treatment with Ac₂O/pyridine the same diacetates, as formed by photooxygenation of (?)-Δ⁸-THC-acetate, were obtained as a 1:1-mixture. On heating these epimeric diacetates to 290° they underwent allylic rearrangement to (?)-11-acetoxy-Δ⁸-THC-acetate. From this (?)-11-hydroxy-Δ⁸-6a, 10a-trans-THC was obtained by treatment with LiAlH₄.     

Methyl 2-benzoylamino-3-dimethylaminopropenoate in the synthesis of heterocyclic systems. The synthesis of benzoyl- amino substituted 7H-pyrano[2,3-d]pyrimidine, 1H,6H-pyrano- [2,3-c]pyrazole and 2H-1-benzopyran derivatives

Methyl 2-benzoylamino-3-dimethylaminopropenoate (6) reacts with heterocyclic compounds containing an active methylene group or potential methylene group in the ring system, such as barbituric acid derivatives 1 and 2, pyrazolones 3 and 4, and resorcinol, in acetic acid to afford the corresponding benzoylamino substituted pyranopyrimidinones 7 and 8 , pyranopyrazolones 9 and 10 , and 2H-1-benzopyranone 11 . The method represents a novel procedure for the preparation of condensed pyranones.     

The enantioselective metabolism of p-cymene in rabbits.

p-Cymene (1) was metabolized in rabbits and the following four optically active metabolites, 2-(p-tolyl)-1-propanol (3': R/S = 65:35), 2-(p-tolyl)propanoic acid (5': R/S = 0:100), p-(2-hydroxy-1-methylethyl)benzoic acid (6': R/S = 91:9) and p-(1-carboxyethyl)benzoic acid (8': R/S = 30:70), were isolated in addition to three optically inactive metabolites, 2-(p-tolyl)-2-propanol (2), p-isopropylbenzoic acid (4'), and p-(1-hydroxy-1-methylethyl)benzoic acid (7'). The presumed metabolic pathways of p-cymene in rabbits were confirmed by the administration of the intermediate metabolites (2, 3', 4', and 5'). The enantiomeric ratios of the metabolites, 3' and 6', suggested that omega-hydroxylations of the isopropyl group in 1 and 4' occurred preferentially at the pro-S methyl group. In the metabolism of 1, the S-isomers are predominant in the propanoic acid derivatives, but the R-isomers are rich in the propanol derivatives. It is of interest that the metabolism of 4', however, produced predominantly the corresponding propanol derivative (6'; R/S = 91:9) and propanoic acid derivative (8'; R/S = 80:20) possessing the same R-configuration. Some optically active p-cymene derivatives were also synthesized as standard compounds.     

Thiopegan derivatives—XVI Synthesis of 10:11-thiopegan derivatives containing a saturated thiazole moiety and of their related compounds

2-Methyl-6-chloro-10:11-thiopegene-9:4-one, 2:7-dimethyl-10:11-thiopegene-9:4-one and the corresponding methylene bases have been synthesized. These methylene thiopegans furnish corresponding isomeric 2-methyl derivatives on acid treatment. 2-Bromomethyl-7-methyl-10:11-thiopega-2:9-diene-4-one has been condensed with piperidine and diethylamine to incorporate the therapeutically important basic moiety in these compounds. New routes to the synthesis of various substituted 2-methyl-10:11-thiopegans and 2-bromomethyl-10:11-thiopega-2:9-diene-4-ones have been developed with a view to improve their yields.     

Synthesis and antimicrobial activity of some derivatives of (7-hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid hydrazide

(7-Hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid hydrazide (2) was prepared from (7-hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid ethyl ester (1) and 100% hydrazine hydrate. Compound 2, is the key intermediate for the synthesis of several series of new compounds such as Schiff's bases 3a-l, formic acid N'-[2-(7-hydroxy-2-oxo-2H- chromen-4-yl)acetyl] hydrazide (4), acetic acid N'-[2-(7-hydroxy-2-oxo-2H-chromen-4- yl)-acetyl] hydrazide (5), (7-hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid N'-[2-(4- hydroxy-2-oxo-2H-chromen-3-yl)-2-oxoethyl] hydrazide (6), 4-phenyl-1-(7-hydroxy-2- oxo-2H-chromen- 4-acetyl) thiosemicarbazide (7), ethyl 3-{2-[2-(7-hydroxy-2-oxo-2H- chromen-4-yl)-acetyl]hydrazono}butanoate (8), (7-hydroxy-2-oxo-2H-chromen-4-yl)- acetic acid N'-[(4-trifluoromethylphenylimino)methyl] hydrazide (9) and (7-hydroxy-2- oxo-2H-chromen-4-yl)acetic acid N'-[(2,3,4-trifluorophenylimino)-methyl] hydrazide (10). Cyclo- condensation of compound 2 with pentane-2,4-dione gave 4-[2-(3,5- dimethyl-1H-pyrazol-1-yl)-2-oxoethyl]-7-hydroxy-2H-chromen-2-one (11), while with carbon disulfide it afforded 7-hydroxy-4-[(5-mercapto-1,3,4-oxadiazol-2-yl)methyl]-2H- chromen-2-one (12) and with potassium isothiocyanate it gave 7-hydroxy-4-[(5- mercapto-4H-1,2,4-triazol-3-yl)methyl]-2H-chromen-2-one (14). Compound 7 was cyclized to afford 2-(7-hydroxy-2-oxo-2H-chromen-4-yl)-N -(4-oxo-2-phenylimino- thiazolidin-3-yl) acetamide (15).     

Synthese von zwei natürlich vorkommenden Lactonen mit 10gliedrigen Ringen: (±)-Phoracantholid J und I

Synthesis of Two Naturally Occurring 10-Membered Ring Lactones: (±)-Phoracantholide J and I Two 10-membered ring lactones 7 and 11 from the metasternal secretion of the eucalypt longicorn Phoracantha synonyma have been synthesized by the following method. Reaction of the dilithium derivative of 4-pentynoic acid ( 3 ) with 4-tetrahydropyranyloxy-1-pentylbromide ( 2 ), followed by removal of the protecting group and by esterification with diazomethane, gave methyl 9-hydroxy-4-decynoate ( 4 ; s. Scheme 1). Partial hydrogenation of the triple bond in 4 with Lindlar palladium catalyst, followed by saponification lead to cis-9-hydroxy-4-decenoic acid ( 6 ). The 9-hydroxydecanoic acid ( 9 ) was synthesized by addition of methyl magnesium iodide to methyl 8-formyloctanoate ( 8 ) followed by saponification (s. Scheme 2). The hydroxy acids 6 and 9 were converted into the S-(2-pyridyl) thioesters and cyclized in dilute benzene solution under the influence of silver ions to yield (±)-phoracantholide J ( 7 ) and I ( 11 ) in 74 and 71% yield, respectively.     

Synthesis of representative 10-aryl-, 10-aralkyl- and 10-heteraryl-9H-naphtho[1′,2′:4,5]thiazolo[3,2-b]- [1,2,4]triazin-9-ones as potential anti-HIV agents

To prepare the title compounds, cyclocondensation of 1-amino-2-iminonaphtho[1,2-d]thiazole ( 2 ) with some representative glyoxylic acid derivatives was investigated. Heating 2 with methyl phenylglyoxylate ( 3a ) in methanol afforded only the open chain intermediates 4a,b . However, when this reaction was performed in re-fluxing glacial acetic acid, the expected compound, 10-phenyl-9H-naphtho[1′,2′:4,5]thiazolo[3,2-b][1,2,4]- triazin-9-one ( 5a ) was produced in 27% yield. Similar treatment of 2 with benzyl-, 2-furyl- and 2-thienylgly-oxylic acids 3b-d gave the corresponding 10-benzyl-, 10-(2-furyl)- and 10-(2-thienyl)-9H-naphtho[1′,2′:4,5]thi-azolo[3,2-b][1,2,4]triazin-9-ones 5b-d in 48–67% yields. As by-products, 9-benzoyl- and 9-(2-thenoyl)naphtho-[1′,2′:4,5]thiazolo[3,2-b][1,2,4]triazoles 6a,d were also isolated. Compound 5a was selected for in vitro anti-HIV evaluation but found to be inactive.     

Synthesis of some azo compounds and a study of their properties

11 azo compounds hitherto undescribed in the literature are synthesized. The azo components used were 8-hydroxyquinoline, resorcinol, pyrogallol, and 7-iodo-8-hydroxy-5-quinolinesulfonic acid, while the diazol components were sulfanilamide and a number of its derivatives. The acid dissociation constants for 8 azo compounds are determined by a solubility method and also spectrophotometrically. The constants are of the order 10^–7-10^–9.     

Isolation of tetraprenyltoluquinols from the brown alga Sargassum thunbergii

Thunbergols A (4) and B (5), tetraprenyltoluquinols, along with three known compounds (1-3) have been isolated from the brown alga Sargassum thunbergii. The structures of these two new compounds were determined to be 9-(3,4-dihydro-2,8-dimethyl-6-hydroxy-2H-1-benzopyran-2-yl)-6-methyl-2-(4-methyl-3-pentenyl)-(2E,6E)-nonadienoic acid (4) and 10-(2,3-dihydro-5-hydroxy-7-methyl-1-benzofuran-2-yl)-10-hydroxy-6-methyl-2-(4-methyl-3-pentenyl)-(2E,6E)-undecadienoic acid (5), respectively, by combined spectroscopic methods. Both of them exhibited significant scavenging activities on radical and potently inhibited generation of ONOO(-) from morpholinosydnonimine (SIN-1).     

Antibacterial thymol derivatives isolated from Centipeda minima

Two new monoterpenoids, 8,10-dihydroxy-9(2)-methylbutyryloxythymol (1) and 10-hydroxy-8,9-dioxyisopropylidene-thymol (2), together with five known thymol derivatives: 8,9,10-trihydroxythymol (3), thymol-beta-glucopyranoside (4), 9-hydroxythymol (5), 8,10-dihydroxy-9-isobutyryloxythymol (6), and 8-hydroxy-9,10-diisobutyryloxythymol (7), were isolated from Centipeda minima. Their structures were identified by means of spectroscopic analyses. Interestingly, compound 2 is not an extraction artifact according to a close HPLC examination of material after extraction by analytical MeOH at ambient temperature. The antibacterial activities of compounds 1-7 were evaluated against eight microbial strains by the agar dilution method.     

Synthetic analogues of Peganum alkaloids. III. Pentamethylenequinazolones

Monosubstituted 5-, 6-, and 8-methoxy-3,4-dihydro-2,3-pentamethylenequinazolones (1–3) have been syntehsized by the condensation of monosubstituted methoxyanthranilic acids with caprolactam. Demethylation with hydrobromic acid gave the corresponding hydroxy compounds [4–6]. When the 6- and 8-methoxy- and 6- and 8-hydroxy-3,4-dihydro-2,3-pentamethylenequinazolones (2, 3, 5, and 6) were reduced with zinc in hydrochloric acid, the corresponding quinazoline derivatives (7–10) were obtained. The melting points of the basis and their hydrochlorides are given. Some features of their UV, mass, and PMR spectra are reported.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 465–469, July–August, 1986.     

Novel,Simple, and Efficient Synthesis of 3-(2-(5-(Benzylideneamino)-3-phenyl-1H-pyrazol-1-yl)thiazol-4-yl)-4-hydroxy-6-methyl-2H-pyran-2-one Derivatives via a One-Pot,Four-Component Condensation Reaction

The synthesis of 3-(2-(5-(benzylideneamino)-3-phenyl-1H-pyrazol-1-yl)thiazol-4-yl)-4-hydroxy-6-methyl-2H-pyran-2-one derivatives was achieved through a one-pot, four-component reaction involving condensation of 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, thiosemicarbazide, phenacylcyanaide, and various aryl aldehydes in dry alcohol and few drops of acetic acid under reflux condition. This four-component reaction has some advantages such as ease of handling, good yields, and easy workup. All structures of newly prepared compounds were confirmed by analytical and spectral data.