Studies on ketene and its derivatives. CXI . Photoreaction of diketene with 2(1H)-quinolone derivatives

Photoreaction of diketene with 4-methyl-2(1H)-quinolone and 1,4-dimethyl-2(1H)-quinolone gave 2R*,2aR*,SbR*- and 2R*,2aS*8bS*-8b-methyl-3-oxo-1,2,2a,3,4,8b-hexahydrocyclobuta[c]quinoline-2-spiro-2′-(oxetan)-4′-one ( 6a and 6b ), and their 4-methyl derivatives 7a and 7b , respectively. Thermolysis of compounds 6 and 7 afforded 2aR*,8bS*-8b-methyl-2-methylene-3-oxo-1,2,2a,3,4,8b-hexahydrocyclobuta[c]quinoline ( 8 ) and its 4-methyl derivatives 9 , respectively. Similarly, photolysis of diketene and 4-acetoxy-2(1H)-quinolone gave 1R*,2aS*,8bS*- and 1R*,2aR*,8bR*-8b-acetoxy-3-oxo-1,2,2a,3,4,8b-hexahydrocyclobuta[c]-quinoline ( 11a and 11b ). Alcoholysis of compounds 11a and 11b with hydrogen chloride in methanol gave 1-hydroxy-1-(methoxycarbonyl)methylcyclobuta[c]quinoline derivative 12 and 13 which were transformed to 4-acetyl-3-methyl-2(1H)-quinolone ( 15 ) by further alcoholysis. Photoreaction of diketene with 2(1H)-quinolone derivatives gave the corresponding cyclobuta[c]quinoline spirooxetanone derivatives 18 and 23 , which, by thermolysis, were transformed to 2-methylenecyclobuta[c]quinoline 23 and 25 , respectively.     

Synthesis of isocoumarin, 1-isoquinolone and 4(1H)-quinolone derivatives via seleno-intermediates

The reaction of 2-styrylbenzoic acids 2 with N-phenylselenosuccinimide (N-PSS) affords 3-phenyl-iso-coumarin derivatives 3 and 3,4-dihydro-3-phenyl-4-(phenylseleno)isocoumarins 4 via selenolactonization. The reaction of 2-styrylbenzamides 5 and 1-(2-aminophenyl)-3-phenyl-2-peropen-1-one derivatives 11 with N-PSS also resulted in the formation of 1-isoquinolone 6 and 4(1H)-quinolone derivatives 12 , respectively.     

Photochromism of 2-benzyl-3-benzoyl-4(1H)-quinolone derivatives

A series of 2-benzyl-3-benzoyl-4(1H)-quinolone derivatives was investigated. The UV–vis spectra of all photochromic derivatives and the corresponding colored photoenols are similar and almost solvent independent. In contrast, the stability of the photoenols depends strongly on the substituents at the quinolone moiety and solvent. We conclude that conversion of the photoinduced forms into the initial quinolones occurs through ionization rather than usual for photochromic compounds thermal relaxation or sigmatropic H-shift. The experimental observations are in good agreement with the results of quantum mechanical calculations.     

Synthesis,Spectroscopic and Electrochemical Studies of Isomeric Dichloro-bis-[ N (1)-Alkyl-2-(Arylazo)Imidazole]-Osmium(II). Single Crystal X-ray Structures of Blue-Violet Dichloro-Bis-[ N (1)-Methyl-2-(Arylazo)Imidazole]-Osmium(II) Species

1-Alkyl-2-(arylazo)imidazoles (p-R-C₆H₄-N=N-C₃H₂N₂X, abbreviated as RaaiX, R = H(a), CH₃(b), Cl(c); X = N(1)-CH₃ (1), N(1)-CH₂-C₆H₅ (2)) have been reacted with (NH₄)₂[OsCl₆] and OsCl₂(RaaiX)₂ species isolated in two isomeric forms, blue-violet (3, 5) and red-violet (4, 6). IR spectra show two x (Os-Cl) modes and support a cis-OsCl₂ configuration. X-ray diffraction methods were used to determine structures of blue-violet isomers. In terms of the three coordination pairs around Os(II), Cl, Cl, N, N (N(imidazole), N) and N', N' (N(azo), N') the blue-violet isomers have a cis-trans-cis (ctc) configuration. ¹H NMR data for the red-violet complexes (isomers B) and results concerning analogous ruthenium(II) complexes indicate isomer B to have cis-cis-cis (ccc) configuration. Absorption spectra show an intense MLCT band at ca 580 nm along with two weak bands at 800 and 1000 nm. Cyclic voltammetry shows quasi-reversible Os(III)/Os(II) and Os(IV)/Os(III) couples at 0.4-0.6 V and 1.3-1.5 V versus SCE and ill-defined azo reductions. The X-Ray structures show unusually long N=N bond lengths, 1.31-1.32 Å, elongated by some 0.06 Å compared to the free ligand value. Os(II) prefers to bind N(azo) (Os-N(azo), 1.98 Å) rather than N(imidazole) (Os-N(imidazole), 2.03 Å). EHMO calculations of ctc-OsCl₂ (MeaaiMe) and comparison with the ruthenium(II) complex account for the MLCT transitions in terms of a metal-dominated HOMO to a ligand-dominated LUMO shift.     

Preparation of Resin-Bound Bismethylene Cyclic Malonic Acid Ester and Facile Solid-Phase Synthesis of 2-Alkylthio-4(1H)-quinolone and 2-Alkyl-4(1H)-quinolone

Abstract

The resin-bound bismethylthiomethylene cyclic malonic acid ester 3 was built up efficiently. Resin 3 can react with arylamines and subsequent thermal cyclizations give 2-alkylthio-4-(1H)-quinolones. Furthermore, conjugate addition of Grignard reagents to the resin 3 forms the resin 6 which was reacted with aryl amines and subsequent thermal-cyclization-cleavages afford the 2-alkyl-4-(1H)-quinolones.     

The transformations of 4-heteroarylaminomethylene-5(4H)-oxazolones into dehydropeptide derivatives

2-Phenyl-4-heteroarylaminomethylene-5(4H)-oxazolones 3 , which were prepared from the corresponding N,N-dimethyl-N'-heteroarylformamidines 1 and hippuric acid 2 in acetic anhydride, react with amino acids giving dehydropeptide derivatives 4, 5 , and 6 as products. Dehydration of N-protected peptides 7–10 , containing glycine at the C-terminal, followed by the reaction with formamidines 1 gave 2-substituted-4-heteroarylaminomethylene-5(4H)-oxazolones 11–14 .     

A facile and novel synthesis of 1,6-naphthyridin-2(1H)-ones

A new and convenient procedure for the synthesis of 1,6-naphthyridin-2(1H)-ones and their derivatives is described. In the first scheme 5-acetyl-6-[2-(dimethylamino)ethenyl]-1,2-dihydro-2-oxo-3-pyridinecarbonitrile ( 4 ) obtained by the reaction of N,N-dimethylformamide dimethyl acetal with 5-acetyl-1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile ( 3 ) was cyclized to 1,2-dihydro-5-methyl-2-oxo-1,6-naphthyridine-3-carbonitrile ( 5 ) by the action of ammonium acetate. Thermal decarboxylation of acid 7 obtained from the hydrolysis of nitrile 5 led to a mixture of 5-methyl-1,6-naphthyridin-2(1H)-one ( 8 ) and its dimer 9 . Hydrazide 11 obtained from nitrile 5 in two steps was converted to 3-amino-5-methyl-1,6-naphthyridin-2(1H)-one ( 12 ) by the Curtius rearrangement. The amino group of 12 was readily replaced by treatment with aqueous sodium hydroxide to yield 3-hydroxy-5-methyl-1,6-naphthyridin-2(1H)-one ( 13 ). In the second scheme, Michael reaction of enamines of type 20 with methyl propiolate, followed by ring closure gave 5-acyl(aroyl)-6-methyl-2(1H)-pyridinones ( 21 ) which in turn were treated with Bredereck's reagent to produce 5-acyl(aroyl)-6-[2-(dimethylamino)ethenyl]-2(1H)-pyridinones ( 22 ). Treatment of 22 with ammonium acetate led to the formation of 1,6-naphthyridin-2(1H)-ones 23 .     

Synthesis of novel 5H‐Pyrimido[5,4‐b]mdole‐(1H,3H)2,4‐diones as potential ligands for the cloned α1‐adrenoceptor subtypes

A new series of 3‐[ω‐[4‐(4‐substituted phenyl)piperazin‐1‐yl]alkyl]‐5H‐pyrimido[5,4‐b]indole‐(1H,3H)‐2,4‐diones ( 3–10 and 12–13 ) were synthesized from the N‐(2‐chloroethyl)‐N'‐[3‐(2‐ethoxycarbonyl)indolyl] urea ( 1 ) or the N‐(3‐chloropropyl)‐N'‐[3‐(2‐ethoxycarbonyl)indolyl] urea ( 2 ) and a number of 1‐(4‐substi‐tuted‐phenyl)piperazines. 3‐[2‐[4‐(4‐Aminophenyl)piperazin‐1‐yl]ethyl]‐5H‐pyrimido[5,4‐b]indole‐(1H,3H)2,4‐dione ( 14 ) was obtained by reduction of the parent nitro compound 8 . The obtained 5H‐pyrimido[5,4‐b]indole‐(1H,3H)2,4‐dione derivatives were tested towards cloned α_1A, α_1B and α_1D adrenergic receptors subtypes in binding assays. Some compounds showed good affinity and selectivity for the α_1D‐adrenoceptor subtype.     

The Synthesis of Some New (S)‐1‐Aryl‐N‐(1‐hydroxy‐3‐phenylpropan‐2‐yl)‐5‐methyl‐1H‐1,2,3‐triazole‐4‐carboxamide

Some new (S)‐1‐aryl‐N‐(1‐hydroxy‐3‐phenylpropan‐2‐yl)‐5‐methyl‐1 H‐1,2,3‐triazole‐4‐carboxamides 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j have been synthesized and established by ¹H and ¹³C NMR, IR, MS spectra, CHN analyses, and x‐ray diffraction crystallography. The molecular conformation and packing is stabilized by interactions of intermolecular H‐bond O2’‐H2'···O1, O2‐H2···O1’ and intramolecular H‐bond N4’‐H4'N···N3’, N4’‐H4'N···O2’, N4‐H4N···N3, N4‐H4N···O2. The two rings of five numbers were formed by H‐bond in a molecular.     

Über 4,4,6-trisubstituierte 3,4-Dihydro-2(1H)-pyrimidinimine,Hexahydro-2(1H)-chinazolinimine bzw.-one bzw.-thione und Spiro[cycloalkan-1,4′(1′H)-cycloalkeno-pyrimidin]-2′ (3′H)-imine

The 2-alken-1-ones2 b, 2 c and3–8, which have very different structures, were reacted with guanidine to give cyclic compounds:2 b and2 c resp. are transformed by guanidine to the trisubstituted 3,4-dihydro-2(1H)-pyrimidinimines1 b and1 c resp., action of guanidine on the cyclo-hexylidenaceton (3) yields 4-methyl-1,3-diaza-4-spiro[5,5]-undecen-2-imine (11); isopropylidencyclohexanone4 and the isomeric (methylcyclohexenyl)ethanone5 condense with guanidine resp. urea resp. NH₄CNS to give 4,4-dimethyl-3,4,5,6,7,8-hexahydro-2(1H)-quinazolinimine (15), resp.-one (16), resp.-thione (17) and 4,8a-dimethyl-3,4,6,7,8,8a-hexahydro-2(1H)-quinazolinthione (19). With the cycloalkyliden-alkanones6–8 guanidine reacts to yield the spiro[cycloalkan-1,4(1H)-cycloalkenopyrimidin]-2(3H)-imines24–26. The structure of the compounds cited is derived from their NMR-and (partially) mass spectra; from most of the bases picrates were also synthesized.

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Herrn Prof. Dr.H. Grubitsch zum 70. Geburtstag gewidmet.     

The preparation of 5-(2-aminophenyl)-1,3,4-oxadiazole-2(3H)-one and its rearrangement to 3-amino-2,4(1H,3H)-quinazolinedione

When anthranilic acid hydrazide is reacted with 1,1-carbonyldiimidazole inTHF 5-(2-aminophenyl)-1,3,4-oxadiazole-2(3H)-one (4) is formed. It can also be prepared from 1-o-aminobenzoyl-4,4-dimethylsemicarbazide which eliminates methylamine when boiled withDMF. On heating the 5-(2-aminophenyl)-1,3,4-oxiadiazole above its melting point it rearranges to 3-amino-2,4(1H,3H)-quinazolinedione (5).

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Die Darstellung von 5-(2-Aminophenyl)-1,3,4-oxadiazol-2(3H)-on und dessen Umlagerung in 3-Amino-2,4(1H,3H)-chinazolindion

Zusammenfassung Bei der Reaktion von Anthranilsäurehydrazid mit 1,1-Carbonyldiimidazol inTHF wird 5-(2-Aminophenyl)-1,3,4-oxadiazol-2(3H)-on (4) gebildet. Dieses kann auch aus 1-o-Aminobenzoyl-4,4-dimethylsemicarbazid dargestellt werden, welches beim Kochen mitDMF Methylamin eliminiert. Beim Erhitzen von 5-(2-Aminophenyl)-1,3,4-oxadiazol über seinen Schmelzpunkt tritt Umlagerung zu 3-Amino-2,4(1H,3H)-chinazolindion (5) ein.

     

Transformation of 4-(1-dimethylaminoethylidene)-2-phenyl-5(4H)-oxazolone into methyl 2-benzoylamino-3-oxobutanoate. The synthesis of 1-substituted 4-benzoylamino-3-methyl-5(2H)-pyrazolones

Methyl 2-benzoylamino-3-oxobutanoate ( 3 ) was prepared from hippuric acid (1) which was converted with N,N-dimethylacetamide and phosphorus oxychloride into 4-(1-dimethylaminoethylidene)-2-phenyl-5(4H)-oxazolone ( 2 ) followed by hydrolysis with hydrochloric acid in methanol. Compound 3 was treated with hydrazines 4 to give 4-benzoylamino-3-methyl-1H-pyrazol-5(2H)-one ( 6a ) and its 1-substituted derivatives 6b-j . The corresponding hydrazones 5f, i, j were isolated as intermediates.     

Synthesis of isomeric N-substituted 5-methyl-2H-1,2,6-thiadiazin-3(6H)one 1,1-dioxides from sulfamides and diketene

The reaction of N-n-butyl and N-benzylsulfamides with diketene in acetic acid solution in the presence of mercuric cyanide as a catalyst, afforded the corresponding 5-methyl-2-substituted-2H-1,2,6-thiadiazin-3(6H)one 1,1-dioxides. The reaction of the above mentioned sulfamides with diketene in an aqueous alkaline medium resulted in the isolation of the corresponding N-aceto-acetyl-N' -substituted-sulfamides, which were then converted into 5-methyl-6-substituted-2H-1,2,6-thiadiazin-3(6H)one 1,1-dioxides. Catalytic hydrogenation of the 5-methyl-2- and 6-n-butyl-2H-1,2,6-thiadiazin-3(6H)one 1,1-dioxides furnished the corresponding dihydro-derivatives. The structures of the isomeric 1,2,6-thiadiazine 1,1-dioxide derivatives obtained were assigned on the basis of nmr spectroscopic studies.     

Synthesis and Characterization of Binuclear (μ-Oxalato) Copper(II) Complexes with N,N′-Diethylethylenediamine or N,N,N′-Trimethylethylenediamine

Three new binuclear w -oxalato copper(II) complexes of composition [(Cu(N,N' -dieten) H₂O)₂ox](ClO₄)₂ ·H₂O (1) (N,N'-dieten = N,N'-diethylethylenediamine, H₂ox = oxalic acid), [(Cu(trimeen)H₂O)₂ox](ClO₄)₂·2H₂O (2) (trimeen = N,N,N'-trimethylethylenediamine) and [(Cu(trimeen)H₂O)₂ox](NO₃)₂ ·2H₂O (3) have been isolated from the reactions of Cu(ClO₄)₂ ·6H₂O (or Cu(NO₃)₂ ·3H₂O), the appropriate amine and Na₂ox in water and have been characterized by IR and electronic spectroscopy and magnetic measurements. The crystal structure of [(Cu(N,N' -dieten)H₂O)₂ ox](ClO₄)₂.H₂O (1) has been determined by single-crystal X-ray analysis. The structure of ( 1 ) consists of binuclear cations [(N,N'-dieten)H₂O)Cu(ox)Cu(N,N'-dieten)H₂O)]²⁺, perchlorate anions and water molecules of crystallization. The copper atom is coordinated by two oxygen atoms of the oxalato ligand, two nitrogen atoms belonging to N,N'-dieten and one oxygen atom of water in a distorted square-pyramidal arrangement. The temperature dependence of magnetic susceptibilities (78-293 K) was measured for 1-3 . Magnetochemical measurements show that copper(II) ions in these compounds are antiferromagnetically coupled with J = -172 cm^-1, -172 cm^-1 and -168 cm^-1 (H = -2JS ₁ S ₂, S ₁= S ₂ = 1/2) for 1, 2 and 3, respectively.     

Über Dihydro-2(1H)-pyrimidinthione

Zusammenfassung 6-Alkyl-3,4-dihydro-2(1H)-pyrimidinthione sind als cyclische Alkenylthioharnstoffe der Addition von Phenolen zu 6-Hydroxyphenyltetrahydro-2(1H)-pyrimidinthionen bzw. derMannich-reaktion zu 6-Dialkylaminoäthylidentetrahydro-bzw. 6-Dialkylaminoäthyldihydro-2(1H)-pyrimidinthionen sowie zu Hexahydro-2(1H)-pyrido[4,3—d]pyrimidinthionen zugänglich. 6-Methylderivate können auch in Dihydro-6-styryl-2(1H)-pyrimidinthione bzw., in einem Fall, in ein Hexahydro-4,4-methylendi-2(1H)-pyrimidinthion umgewandelt werden.

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Dihydro-2(1H)-pyrimidinethiones (Heterocycles, XXI)

6-Alkyl-3,4-dihydro-2(1H)-pyrimidinethiones (cyclic alkenylthio carbamides) add phenoles to give 6-hydroxyphenyltetrahydro-2(1H)-pyrimidinethiones and undergoMannich reaction, to give 6-dialkylaminoethylidentetrahydro-and 6-dialkylaminoethyldihydro-2(1H)-pyrimidinethiones and hexahydro-2(1H)-pyrido[4,3—d]pyrimidinethiones, resp. 6-Methyl derivatives can also be transformed into dihydro-6-styryl-2(1H)-pyrimidinethiones resp., in one case, into a hexahydro-4,4-methylendi-2(1H)-pyrimidinethione.

     

Synthese und Reaktionsverhalten von 3-(Bis(alkylthio)methylen)-3H-isobenzofuran-1-on-und 2-(Bis(alkylthio)methylen)-3(2H)-benzofuranon-Derivaten

Summary 3(Bis(alkylthio)methylene)-3H-isobenzofuran-1-ones2a–e and 2-(bis(alkylthio)methylene)-3(2H)-benzofuranone derivatives4a–c are obtained by reaction of phthalides1a–d or 3(2H)-benzofuranone (coumaranone3), respectively, with carbon disulfide under basic conditions followed by alkylation. The reaction behaviour of the new compounds2 and4 is investigated. 2-((2-Dimethylthio-1-oxo)ethyl)benzoic acid N,N-dimethylamide (7a) and 2-((2-dimethylthio-1-oxo)ethyl)-benzoic acid 2-methylpiperidide (7b) are surprisingly formed instead of the methylthio substitution products by treatment of2a with the corresponding amine in the presence of aluminum chloride.

Herrn Professor Dr. Dr. h. c.Waldemar Adam zum 60. Geburtstag gewidmet     

Reduction products of 3(2H)-cinnolinones

Reduction of 3(2H)-cinnolinone with zinc and ammonium hydroxide forms 1,4-dihydro-3(2H)-cinnolinone which rapidly rearranges to 1-amino-2-indolinone (1-aminooxindole) in acid solution. 1,4-Dihydro-2-methyl-3(2H)-cinnolinone is formed from 2-methyl-3(2H)-cinnolinone under the same conditions, but its rearrangement to 1-(N-methylamino)-2-indolinone (1-(N-methylamino)oxindole) in acid solution is much slower.     

Photochemical Reactions of Tetrahydroquinoxalin-2(1H)-ones and Related Compound

Photochemical behaviors of the pyrazinone derivatives 5,6,7,8-tetrahydroquinoxalin-2(1H)-ones 1a – c and 1,5,6,7,8,9-hexahydro-2H-cyclohepta[b]pyrazin-2-one 1d were investigated. Dye-sensitized photo-oxygenation of 1a-c gave the 1:1 adducts 5a – c of the corresponding 3,8a-epidioxy-3,5,6,7,8,8a-hexahydroquinoxalin-2(1H)-one 4 and H₂O, whereas 1d gave 3,9a-epidioxy-1,3,5,6,7,8,9,9a-octahydro-2H-cyclohepta[b]pyrazin-2-one 4d (Scheme 2). The different kind of products was interpreted as being the result of the ring strain and steric hindrance of endoperoxides produced from 1a – d with singlet oxygen. Irradiation of 1a – b in the presence of alkenes gave tricyclic azetidine derivatives 9 by [2 + 2] cycloaddition of the C?N bond of 1 to the alkene.     

Synthesis and transformations of (±)-trans-4aβ(H), saα(H)-octahydro-4α,7β-dimethyl-2H-1-benzopyran-2-one

Hydrogenation of 4,7-dimethylcoumarin ( 1 ) in alkaline medium has been shown to furnish a mixture of (±)-trans-4aβ(H),8aα(H)-octahydro-4α,7β-dimethyl-2H-1-benzopyran-2-one ( 2 ), (±)-trans-4aβ(H),8aα(H)-octahydro-4α,7α-dimethyl-2H-1-benzopyran-2-one ( 3 ) and (±)-cis-4aα(H),8aα(H)-octahydro-4α,7α-dimethyl-2H-1-benzopyran-2-one ( 4 ) in 40:25:35:ratio, respectively. The stereochemistry of the major hydrogenation product 2 , has been established by transforming it to p-menthane derivatives e.g. (±)-2 (R)-[2′(R)hydroxy-4′(R) methylcyclohex-(1′S)-yl]propan-1-ol ( 20 ) and (±)-trans-3α,6β-dimethyl-3aβ(H),7aα(H)-octahydrobenzofuran ( 12 ). Starting from a mixture of lactones 2, 3 and 4 , lactone 3 has been obtained in pure state employing a sequence of reactions.     

Practical Synthesis of 4-Benzylidene-2-phenyl-5(4H)-oxazolones

A simple and alternative method has been developed for the synthesis of 4-benzylidene-2-phenyl-5(4H)-oxazolones via reactions of hippuric acid with various aldehydes in the presence of 2-chloro-4,6-dimethoxy-1,3,5-triazine/N-methylmorpholine at 75 °C.

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