Synthesis and Antimicrobial Activities of Some 6-Methyl-3-Thioxo-2,3-Dihydro-1,2,4-Triazine Derivatives

Abstract

4-Arylidene-imidazole derivatives (4a,b) were readily prepared by reacting 4-am- ino-6-methyl-3–thioxo-2,3–dihydro[1,2,4]triazin-5(4H)-one (1) with 4-arylidene-2-phenyl- 4H-oxazol-5-one (2). Reaction of 1 with some aromatic aldehydes in presence of triethylphosphite exclusively afforded the corresponding aminophosphonates 5a-c. Reaction of 1 with 3-phenyl-1H-quinazoline-2,4-dione (6a) and/or 3-phenyl-2-thioxo-2,3-dihydro- 1H-quinazolin-4-one (6b) gave 2-(6-methyl-5-oxo-3-thioxo-2,5-dihydro-3H-[1,2,4]triazin-4-ylimino)-3-phenyl-2,3-dihydro-1H-quinazolin-4-one (7). Moreover, on treating 1 with 2-phenylbenzo[d][1,3]thiazine-4-thione (8), 6-methyl-4-(2-phenyl-4-thioxo-4H-quinazolin-3-yl)-3-thioxo-3,4-dihydro-2H-[1,2,4]triazine-5-one (9) was obtained in 65% yield. Reaction of 1 with 4-sulfonylaminoacetic acid derivatives (10a,b) afforded the corresponding sulfonamides (11a,b), respectively. Acid hydrolysis of 11a afforded 7-aminomethyl-3-methyl[1,3,4]thiadiazole[2,3-c][1,2,4]triazin-4-one (12). 4-Amino-6-methyl-3-(morpholine-4-ylsulfanyl)-4H-[1,2,4]triazin-5-one (14) was prepared by reacting compound 1 with morpholine in presence of KI/I₂, while 3,3′-bis(4-amino-6-methyl-5-oxo-triazinyl)disulfide (16) was obtained by oxidation of 1 with lead tetraacetate. The antimicrobial activity of the products was evaluated against Gram-positive and Gram-negative bacteria as well as the fungus Candida albicans.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures, and tables.]     

NOVEL N,S-SUBSTITUTED DIENES BY THE REACTION OF 2-NITROTHIOSUBSTITUTED HALODIENES AND PRIMARY AMINES

Mono(thio)substituted 1a–c gave compounds 3a–c and 5a with o-toluidin (2) and m-toluidin (4) in ether. Compounds 9a–c and 11a, b were obtained from the reaction of compounds 1a–c with p-fluorophenylamine (8) and p-fluorobenzylamine (10). Compounds 7a and 15c were obtained from the reaction of 1a and 1c with p-phenylendiamine (6) and o-phenylendiamine (14). Compound 13c was synthesized from the reaction of compound 1c with benzidine (2).     

A study of the Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one derivatives

Summary The Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 a) gave 7-hydroxy-8-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (3 a) and 2,3-dihydro-2,6-diphenyl-3-methyl-(7H)furo[2,3-h]-1-benzopyran-7-one (7 a). 2-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 b) afforded4 b and7 b. 8-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (12) gave only the alkali soluble product 7-hydroxy-8-methyl-6-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (13).3 a,4 b, and13 were further cyclized in acidic medium to9 a,10 b, and14 followed by dehydrogenation.This paper is dedicated to Dr. F. M. Dean, Department of Organic Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, U. K., on his retirement     

THE CRYSTAL STRUCTURES OF TWO IMINO-1,2,4- DITHIAZOLES FORMED BY THERMAL DECOMPOSITION OF 5-(DIALKYLAMINO)-3-(SUBSTITUTED IMINO)-1,2,4-DITHIAZOLES

Abstract

The thermal decomposition products of two substituted imino-1,2,4-dithiazoles have been studied by single crystal x-ray analysis. Both products crystallize in space group P2^1/c with four molecules per unit cell. The first product, obtained from 5-(dimethylamino)-3-(methylimino)-1,2,4-dithiazole has cell dimensions of a=9.922(8) Å, b=12.052(11) Å, c=13.358(12) Å and β=104.9(1)°. The molecule is made up of two planar segments related by an extremely large twist (?154°) about a C?N double bond. The results from this study have also contributed further information in the area of nonbonded interactions between ring and thione sulfur atoms. The second product, from 5-(dimethylamino)-3(phenylimino)-1,2,4-dithiazole was shown to be an ordered 1:1 complex of the starting material and one of its isomers. The cell dimensions are a=12.420(6) Å, b=8.840(9) Å, c=22.276(22) Å and β= 112.2(1)°. The different molecules are linked by an inter molecular NH… N hydrogen bond.     

Saturated heterocycles, 75. Preparation of tetracyclic thiophene derivatives with bridgehead nitrogen. Synthesis of polymethylenethieno[2,3—d]dihydropyrrolo-, tetrahydropyrido- and tetrahydroazepino[1,2—a]pyrimidin-4-ones and -4-thiones

The following tetracyclic ring systems and their derivatives have been synthesized for pharmacological investigations: Trimethylenethieno[2,3—d]dihydropyrrolo[1,2—a]pyrimidin-4-one and -4-thione (1 a, 5 a); Tetramethylenethieno[2,3—d]dihydropyrrolo[1,2—a]pyrimidin-4-one and -4-thione (1 b, 1 j, 5 b); Pentamethylenethieno[2,3—d]dihydropyrrolo[1,2—a]pyrimidin-4-one and-4-thione (1 c, 5 c); Trimethylenethieno[2,3—d]tetrahydropyrido[1,2—a]pyrimidin-4-one and -4-thione (1 d, 5 d); Tetramethylenethieno[2,3—d]tetrahydropyrido[1,2,—a]pyrimidin-4-one and -4-thione (1 e, 5 e); Pentamethylenethieno[2,3—d]tetrahydropyrido[1,2—a]pyrimidin-4-one and -4-thione (1 f, 5 f); Trimethylenethieno[2,3—d]tetrahydroazepino[1,2—a]pyrimidin-4-one and -4-thione (1 g, 5 g); Tetramethylenethieno[2,3—d]tetrahydroazepino[1,2—a]pyrimidin-4-on and -4-thione (1 h, 5 h); Pentamethylenethieno[2,3—d]tetrahydroazepino[1,2—a]pyrimidin-4-one and -4-thione (1 i, 5 i); Tentamethylenethieno[2,3—d]tetrahydroazepino[1,2—a]pyrimidin-4-one (7 b); Pentamethylenethieno-[2,3—d]tetrahydropyrido[1,2—a]pyrimidin-4-one (7 c).Compounds1 a–i were synthesized from 2-amino-3-ethoxycarbonyl-4,5-polymethylenethiophene2 a–c with the corresponding lactim ethers (3 a–c) in chlorobenzene in the presence of polyphosphoric acid (PPA). Compounds7 b and7 c were obtained in the reaction of -amino acid esters2 b and2 c with 2-bromopyridine (6). The thione derivatives (5 a–i) were prepared from compounds1 a–i with phosphorus(V) sulphide.Part 74:Szabó J, Fodor L, Szcs E, Bernáth G, Sohár P (1984) Pharmazie 39: 347.     

HYDROXYALKANESULFONYL CHLORIDES FROM CHLORINATION OF HYDROXYALKANESULFINATE SALTS IN A NONPOLAR MEDIUM: 3-HYDROXY-1-PROPANESULFONYL AND 4-HYDROXY-1-BUTANESULFONYL CHLORIDES

Abstract

3-Hydroxy-1-propanesulfonyl chloride (1b) was obtained for the first time (admixed with 10% of propane sultone, 2b) by chlorination of a dichloromethane suspension of sodium 3-hydroxy-1-propanesulfinate (3b). 4-Hydroxy-1-butanesulfonyl chloride (1c) containing 13% butane sultone (2c) was prepared similarly from 3c. The cyclizations of 1b and 1c in CDCl₃ containing 1-butanol (0.9 M) showed first order rate constants of 1.4 × 10^?4 and 6.4 × 10^?5 s^?1, corresponding to effective concentrations of 4.5 × 10² and 2.1 × 10² M, respectively. Reaction of triethylamine in ethanol-d (a) with 1b gave exclusively the undeuterated sultone (2b), evidently by a direct cyclization, and (b) with 1c produced mainly ethyl 4-hydroxy-1-butanesulfonate largely monodeuterated at the α-position, and presumably formed by way of the sulfene (6c).     

THE NOVEL MACROCYCLIC AND LINEAR-CHAIN THIOETHERS FROM PERCHLOROBUTADIENE AND DITHIOLES

Compounds 3a–c, 4a, b, 5a–c, and 6a, c were obtained from the reactions of perchlorobutadiene (1) with 1,4-butanedithiol (2a), 1,5-pentanethiol (2b), and 2.2′-(ethlene-dioxyl)diethanethiol (2c) in ethanol in the presence of sodium hydroxide. Compounds 7a, b were obtained from the reactions of thioethers 3a, b with m-chlorperbenzoic acid in CHCl ₃ .     

Synthesis of 2-(2-methoxyethyl)- and 2-(2-thiomethoxyethyl)-aniline and related compounds

Summary 2-(2-Nitrophenyl)-ethanol (2) was methylated with dimethyl sulfate to give 2-(2-methoxyethyl)-1-nitrobenzene (3a) which then was reduced with hydrazine hydrate in the presence ofRaney nickel to 2-(2-methoxyethyl)-aniline (1a). Compound1a can be transformed into the N-monosilylated derivative4 by lithiation withn-butyllithium and subsequent reaction with chlorotrimethylsilane. Reaction of2 withp-toluenesulfonyl chloride yields 2-(2-nitrophenyl)-ethylp-toluenesulfonate (5), which reacts with sodium thiomethoxide to give 2-(2-nitrophenyl)-ethylp-toluenesulfonate (5), which reacts with sodium thiomethoxide to give 2-(2-thiomethoxyethyl)-1-nitrobenzene (3b).3b was reduced with hydrazine hydrate in the presence ofRaney nickel to yield 2-(2-thiomethoxyethyl)-aniline (1b). Ethyl (2-nitrophenyl)-acetate (6) could be dimethylated with methyl iodide in the presence of potassiumtert-butoxide and 18-crown-6 to give ethyl 2-methyl-2-(2-nitrophenyl)-propionate (7). Reduction of7 with lithium borohydride yields 2,3-dihydro-3,3-dimethyl-1H-indole (9) and 2-[(1-hydroxy-2-methyl)-2-propyl]-aniline (10).

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Synthese von 2-(2-Methoxyethyl)- und 2-(2-Thiomethoxyethyl)-anilin und verwandten Verbindungen

Zusammenfassung 2-(2-Nitrophenyl)-ethanol (2) wurde mit Dimethylsulfat zu 2-(2-Methoxyethyl)-1-nitrobenzol (3a) methyliert, das sich mit Hydrazinhydrat in Gegenwart vonRaney-Nickel zu 2-(2-Methoxyethyl)-anilin (1a) reduzieren läßt. Verbindung1a kann durch Metallierung mitn-Butyllithium und anschließende Reaktion mit Chlortrimethylsilan in dasN-monosilylierte Derivat4 umgewandelt werden. Reaktion von2 mitp-Toluolsulfonylchlorid ergab 2-(2-Nitrophenyl)-ethyl-p-Toluolsulfonat (5), das mit Natriumthiomethanolat zu 1-Nitro-2-(2-thiomethoxyethyl)-benzol (3b) reagiert.3b wurde mit Hydrazinhydrat in Gegenwart vonRaney-Nickel zu 2-(2-Thiomethoxyethyl)-anilin (1b) reduziert. Ethyl-2-(nitrophenyl)-acetat (6) kann mit Methyliodid in Gegenwart von Kalium-tert-butoxid und 18-Krone-6 zu Ethyl-2-methyl-2-(2-nitrophenyl)-propionat (7) dimethyliert werden. Reduktion von7 mit Lithiumborhydrid lieferte 2,3-Dihydro-3,3-dimethyl-1H-indol (9) und 2-[(1-Hydroxy-2-methyl)-2-propyl]-anilin (10).

     

Solvent-Free Synthesis of Novel Highly Functionalized Dihydroanthra[1,2-b]furan-6,11-dione Derivatives

A convenient and environmentally friendly solvent-free procedure has been developed to react 1,5-dihydroxyanthraquinone with dialkyl acetylenedicarboxylates in the presence of triphenylphosphine in one pot to afford novel dialkyl (E)-2-{1,5-dihydroxy-6-[3-methoxy-1-(methoxycarbonyl)-3-oxo-2-(triphenyl-λ ⁵-phosphanylidene)propyl]-9,10-dioxo-9,10-dihydro-2-anthracenyl}-2-butanedioate 3a–c. As a result of intramolecular nucleophilic attack at 90 °C, novel dialkyl (E)-2–{2,7-dihydroxy-3-[2-methoxy-2-oxo-1-(triphenyl-λ ⁵ phosphanylidene)ethyl]-6,11-dioxo-6,11-dihydroanthra[1,2-b]furan-8-yl}-2-butanedioates 4a–c were produced in good yield.     

Utility of 1‐Chloro‐3,4‐dihydronaphthalene‐2‐carboxaldehyde in the Synthesis of Novel Heterocycles with Pharmaceutical Interest

Ethyl α‐cyano‐β‐(1‐chloro‐3,4‐dihydronaphthalene‐2‐yl) acrylate (2) was prepared by the Knoevenagel condensation of 1 with ethyl cyanoacetate. Compound 2 was used as the key intermediate to prepare Schiff bases (3a, b), benzo[c]acridine (4), naphthyl thiopyrimidine (5), and pyrazolo[2,3‐a]‐benzo[h]quinazoline (6) derivatives through its reaction with hydrazines, p‐ansidine, thiourea, and 3,5‐diamino‐4‐phenylazopyrazole, respectively. Base‐catalyzed cyclocondensation of 1 with hippuric acid gives oxazolone derivative (7). Reaction of compound 7 with aniline gave imidazolone derivative (9). Treatment of compound 1 with different types of diaminopyrazoles gave 6,7‐dihydro‐pyrazolo[2,3‐a]‐benzo[h]quinazoline (10–13) derivatives. The multicomponent reaction of compound 1 with pyrazolone and malononitrile in the presence of ammonium acetate furnished pyrazolo[3,4‐b]‐benzo[h]quinoline (14) while in the presence of piperidine afforded benzo[h]chromeno[2,3‐c]pyrazole derivative 15.     

STRUCTURES OF PYRIDINE CARBOXYLATE COMPLEXES OF COBALT(II) AND COPPER(II)

Abstract

The syntheses and crystal structures of [Co(nic)₂(H₂O)₄] (1). [Co(iso)₂(H₂O)₄] (2). [Cu(nic)₂(H₂O)₄] (3), and [Cu(iso)₂(H₂O)₄] (4) (nic = nicotinate; iso = isonicotinate) are reported. Complex 1 crystallizes in monoclinic, space group C2/m with cell parameters a =14.150(4). b = 6.883(2)., c = 8.497(2) Å, β= 118.28(2)° and Z = 2. The other crystals. 2. 3. and 4. are all triclinic, Pī; a = 9.777(3), b = 6.348(4), c = 6.888(3)Å, a= 113.10(6)., β= 110.55(3). γ = 97.61(5)°, and Z=l for 2; a = 7.0281(4), b = 7.7176(6), c = 8.6978(7)Å, a = 68.103(7), β = 68.526(5), γ = 62.550(6)°, and Z=1 for 3; a = 9.1807(4), b = 6.3334(3), c = 6.8871(3)Å, a= 108.213(4), β = 99.433(4), γ= 105.190(4)°, and Z= 1 for 4. The arrangements around the metal ions are trans-octahedra with two pyridyl nitrogens and two aqua oxygens in the equatorial positions and two aqua oxygens in the axial positions, although the Cu(II) complexes show a larger Jahn-Teller distortion.     

Darzens reaction as a convenient method for the synthesis of α-chloroketones, α-chloroepoxides,and symmetrically substituted dioxines

Summary TheDarzens reaction of dichloroacetophenone (DCAP) with substituted benzaldehydes has been studied. The structure of the products was shown to depend on the phenyl group substituents. Reaction of benzaldehyde, 4-bromo-, and 2,4-dichlorobenzaldehydes results in 1-phenyl-3-aryl-3-chloropropane-1,2-diones (2a–c), reaction ofpara- ormeta-nitrobenzaldehydes yields 1-phenyl-2-chloro-3-aryl-2,3-epoxypropane-1-ones (3a, b). Upon the introduction of an alkoxy group into the phenyl ring of benzaldexyde and/or dichloroacetophenone, symmetrically substituted dioxines were obtained (6a–c). The structure of the reaction products has been established by single crystal X-ray investigations.

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Darzens-Reaktion als bequemes Verfahren zur Synthese von -Chloroketonen, -Chloroepoxiden und symmetrisch substituierten Dioxinen

Zusammenfassung DieDarzens-Reaction von Dichloracetophenon (DCAP) mit substituierten Benzaldehyden wurde untersucht. Die Struktur der Produkte ist von den Substituenten an der Phenylgruppe abhängig. Die Umsetzung mit Benzaldehyd, 4-Brom- und 2,4-Dichlorbenzaldehyd liefert 1-Phenyl-3-aryl-3-chloropropan-1,2-dione (2a–c), die Reaktion vonpara- odermeta-Nitrobenzaldehyd 1-Phenyl-2-chloro-3-aryl-2,3-epoxipropan-1-one (3a,b). Durch Einführung einer Alkoxygruppe in den Phenylring des Benzaldehyds und/oder des Dichloracetophenons erhält man symmetrisch substituierte Dioxine (6a–c). Die Struktur der Reaktionsprodukte wurde mittels Röntgenstrukturanalyse bestätigt.

     

Synthesis of Heteroanellated Pyranosides Starting from Methyl 4,6‐O‐benzylidene‐2,3‐dideoxy‐α‐d‐erythro‐hexopyranosid‐2‐ylidenemalononitrile

The hexopyranosid‐2‐ylidenemalononitrile 1 reacted with phenyl isothiocyanate in the presence of triethylamine to furnish (2R,4aR,6S,10bS)‐8‐amino‐4a,6,10,10b‐tetrahydro‐6‐methoxy‐2‐phenyl‐10‐phenylimino‐4H‐thiopyrano[3′,4′:4,5]pyrano[3,2‐d][1,3]dioxine‐7‐carbonitrile (2). Starting from 1, cyclization with sulphur and diethylamine yielded (2R,4aR,6S,9bR)‐8‐amino‐4,4a,6,9b‐tetrahydro‐6‐methoxy‐2‐phenylthieno[2′,3′:4,5]pyrano[3,2‐d][1,3]dioxine‐7‐carbonitrile (3), which could be transformed into the corresponding aminomethylenamino derivative 4 by treatment with triethyl orthoformate and ammonia. Intramolecular cyclization of 4 to yield (2R,4aR,6S,11bR)‐4,4a,6,11b‐tetrahydro‐6‐methoxy‐2‐phenyl[1,3]dioxino[4″,5″:5′,6′]pyrano[3′,4′:4,5]thieno [2,3‐d]pyrimidin‐7‐amine (5) was achieved by using NaH as base. (2R,4aR,6S,9bS)‐8‐Amino‐4a,6,9,9b‐tetrahydro‐6‐methoxy‐9‐(4‐methylphenyl‐sulfonyl)‐2‐phenyl‐4H‐[1,3]dioxino[4′,5′:5,6]pyrano[4,3‐b]pyrrole‐7‐carbonitrile (6) was prepared by treatment of compound 1 with tosylazide and triethylamine.     

SYNTHESIS OF (2,3,4,6-TETRA-O-ACETYL-α-D-GLYCOPYRANOSYL) THIOPHENE DERIVATIVES AS NEW C-NUCLEOSIDE ANALOGUES[1]

Treatment of 2-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)ethanal (1a) and 2-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)ethanal (1b) respectively with malononitrile in the presence of silica gel provided the corresponding 4-[2,3,4,6-tetra-O-acetyl-α-D-glycopyranosyl]-2-cyanocrotononitriles (2a) and (2b). Starting from 2a and 2b, respectively, cyclizations with sulfur and triethylamine yielded 5-[2,3,4,6-tetra-O-acetyl-α-D-glycopyranosyl]-2-aminothiophene-3-carbonitriles (3a) and (3b). Further cyclizations could be achieved by utilizing of triethyl orthoformate/ammonia to furnish the 6-(α-D-glycopyranosyl)thieno[2,3-d]pyrimidine-4-amines 4a and 4b.     

Zur Umsetzung des 3,4,5,6-Tetrahydro-6-hydroxy-4,4,6-trimethyl-1,3-thiazin-2-thions mit primären Aminen

Tetrahydro-6-hydroxy-4,4,6-trimethyl-1,3-thiazine-2-thione (1 a) reacts with methyl-, ethyl- and n-butylamine to the corresponding 1-alkyl-6-alkylaminotetrahydro-2(1H)-pyrimidinethione12 but withi-propylamine to tetrahydro-6-isopropylamino-1,3-thiazine-2-thione (6 d). On treatment withDCC,6 d is rearranged to dihydro-4-isopropylamino-2(1H)-pyridinethione (8 d), and 6-amino-tetrahydro-1,3-thiazinethione (6 a) to dihydro-4,4,6-trimethyl-2(1H)-pyrimidinethione (10 a). The reaction of 6-aminothiazinethiones6 a, d and 6-(4-morpholinyl)-thiazinethione13 resp., with methylamine leads to 1-methyl-6-methylamino-pyridinethione12 b. 1-Alkyl-6-alkylamino-tetrahydro-2(1H)-pyrimidinethiones (12) react at reflux temperature to dihydro-1-alkylpyrimidinethiones10. With methylamine only 6-methylamino-3,4,4,6-tetramethyl-1,3-thiazine-2-thione (6 f) is formed from tetrahydro-6-hydroxy-tetramethyl-1,3-thiazine-2-thione (1 b).     

Ozonolyse von Olefinen,III: Säurekatalysierte Ozonolyse von 3-Hexen-1,6-und 2-Penten-1,5-dicarbonylderivaten

Summary The ozonolysis of mono-unsaturated compounds containing the structural element =CH-CH₂-R [R=COOH, COOCH₃, CH(OCH₃)₂] was investigated. Reductive ozonolysis of (E)-3-hexene-1,6-dioic acid gives methyl 3,3-dimethoxypropanoate (2), whereas ozonolysis of dimethyl (E)-3-hexene-1,6-dioate (1a) and (Z)-1,1,6,6-tetramethoxy-3-hexene (1b) in a methanolic solution of HCl leads to a mixture of2, dimethyl malonate (3 a) and 1,1,3,3-tetramethoxypropane (3 b). The homologuos derivatives, dimethyl glutaconate (4 a) and 1,1,5,5-tetramethoxy-2-pentene (4 b), were ozonized to give mixtures of2, 3, dimethyl oxalate (5), methyl 2,2-dimethoxyacetate (6 a), and 1,1,2,2-tetramethoxyethane (6 b). The ratios of the various reaction products were determined by gas chromatography. In each case the formation of the bifunctional derivatives2 and6 a was favoured.

     

Synthesis of Dihydrobenzo[h]coumarins and Their 4‐Methyl Analogs

Dihydrobenzo[h]coumarins (5a–7a) and their 4‐methyl analogs (5b–7b) were synthesized from 1‐naphthol via two different synthetic routes. One pathway is the direct condensation of 5,8‐dihydro‐1‐naphthol (9) with malic acid or ethyl acetoacetate, affording 7,10‐dihydrobenzo[h]coumarins 7a and 7b, respectively. The other is through the oxidation of 7,8,9,10‐tetrahydrobenzo[h] coumarins (15a–b), followed by the reduction of the carbonyl group and dehydration of hydroxyl group, giving 7,8-dihydrobenzo[h]coumarins (5a, b) and 9,10-dihydrobenzo[h]coumarins (6a, b). The regio selectivities for the oxidation reactions of 15a, b were rationalized on the basis of quantum chemical calculations and further confirmed by the X‐ray crystallographic analysis of the derivatives of oxidation products.     

Kondensierte Heterocyclen aus β-Isothiocyanatoketonen und Aminocarbonsäuren

On reaction of glycine, anthranilic acid and anthranilamide respectively with 4-isothiocyanato-4-methyl-2-pentanone (1), derivatives of condensed heterocycles (oxazolopyrimidine5, pyrimidobenzoxazine7 a, pyrimidobenzodiazine7 c) are formed. The same holds for the reaction of dithiocarbamates, prepared from glycine and CS₂ in aqueous NaOH, with 4-methyl-3-penten-2-one and cinnamaldehyde respectively (12 a, b). The reaction of hot dimethylformamide with7 a leads under initial aminolysis to pyrimidine-anthranildimethylamide2 i; this is subsequently transformed partly through methylpyrimidine-pyridine rearrangement into the N-4-pyridine-anthranil-N,N-dimethylamide10 d, partly under further aminolysis byDMF followed by rearrangement to the dimethylaminodihydro-2(1H)-pyridinethione10 c. 5 is converted to dihydro-4-methylamino-2(1H)-pyridinethione (10 a) in boiling hexanol and2 c to n-hexyl-3-(tetrahydrothioxo-pyridylamino)-propionate (10 b).     

Synthesis and reactions of 2,3-dimethylfuro[3,2-c]pyridines

Summary A number of substituted 2,3-dimethylfuro[3,2-c]pyridines was synthesized. 3-(4,5-Dimethyl-2-furyl)propenoic acid (1) was converted to the acid azide2, which in turn was cyclized to give 2,3-dimethyl-5H-furo[3,2-c]pyridine-4-one (3) by heating at 240°C in Dowtherm. The pyridone3 was chlorinated with phosphorus oxychloride to give4, which was reduced with zinc and acetic acid to 2,3-dimethylfuro[3,2-c]pyridine (5). Treatment of4 with several secondary heterocyclic amines led to compounds6a–6c. Reaction of pyridone3 with phosphorus pentasulfide rendered the thione7, which was methylated to8a. The 4-methoxy derivative8b was obtained from4 with sodium methoxide. 2,3,5-Trimethylfuro[3,2-c]pyridine-4-one (9) was obtained by reaction of3 with methyl iodide.Dedicated to Professor Dr.Fritz Sauter on the occasion of his 65th birthday     

SYNTHESIS OF NEW ANTHRACYCLINE DERIVATIVES CONTAINING PYRUVIC,ASPARTIC, OR N-ACETYLASPARTIC ACID MOLECULE

ABSTRACT

The new anthracycline analogues (2–10) as potential anticancer agents were synthesized from daunomycin (1a) and doxorubicin (1b). Compounds 2, 6, and 7 were prepared by the nucleophilic displacement type esterification of a 14-bromodaunomycin (1c) with a sodium pyruvate, aspartate, and N-acetylaspartic acid, respectively. Whereas compounds (3, 8) and (4, 9) were prepared by the reaction of daunomycin (1a) or doxorubicin (1b) with one equivalent of the corresponding acids in the presence of EDCI/PP, compounds (5, 10) were obtained from 1b by reaction with two equivalents of the corresponding acids in the same manner.