4-Substituted-3-alkyl-3,4-dihydro-2H-1,3-benzoxazin-2-ones. IV (2-4). Keto-Enol tautomerism of β-keto ester derivatives. Reaction of β-dicarbonyl compounds with diamines

A series of α-[3-alkyl-3,4-dihydro-2-oxo-2H-1,3-benzoxazin-4-yl]-β-keto ester derivatives 1 (Table I) were synthesized by the condensation of 3-alkyl-3,4-dihydro-4-hydroxy-2H-1,3-benzoxazine-2-ones 3 (2) with β-keto esters 4 in the presence of traces of mineral acids under azeotropic conditions. Condensation of 1 with hydrazines 5 gave pyrazolone derivatives 2 (Table II). Condensation of β-diketone derivatives 6 with hydrazines 5 and with 1,2-benzenediamine ( 8 ) resulted in the formation of pyrazoles ( 7a-c ) and diazepine derivatives 12 (Table III) and 13 , respectively.     

4-Substituted-3,4-dihydro-3-methyl-2H-1,3-benzoxazin-2-ones. III (2,3). Solvolytic-reductive transformation of 4-(2-keto)-benzoxazin-2-ones into oxazin-2-ones

A series of 4-(2-keto-substituted)-3,4-dihydro-3-methyl-2H-1,3-benzoxazin-2-ones 1 (Table I) was synthesized by condensation of 3-alkyl-3,4-dihydro-4-hydroxy-2H-1,3-benzoxazin-2-ones 4 with ketones 5 having active alpha hydrogens. In the presence of alcoholic potassium borohydride, compounds 1 underwent reductive transacylation to give 1,3-oxazin-2-one derivatives 3 (Table III, a,b,c). When the other side of the ketone possessed substituents other than hydrogen, there were always also normal reduction products, i.e., secondary alcohols 2 (Table II) in addition to 3.     

Cob(I)alamin als Katalysator, 5. Mitteilung [1]. Enantioselektive Reduktion α,β-ungesättigter Carbonylderivate

Cob(I)alamin as Catalyst. 5. Communication [1]. Enantioselective Reduction of α,β-Unsaturated Carbonyl Derivatives The cob(I)alamin-catalyzed reduction of an α,β-unsaturated ethyl ester in aqueous acetic acid produced the (S)-configurated saturated derivative 2 with an enantiomeric excess of 21%. The starting material 1 is not reduced at pH = 7.0 in the presence of catalytic amounts of cob(I)alamin (see Scheme 2). It is shown that the attack of cob(I)alamin and not of cob(II)alamin, also present in Zn/CH₃COOH/H₂O, accounts for the enantioselective reduction observed. All the (Z)-configurated starting materials 1 , 3 , 5 , 7 , 9 and 11 have been transformed to the corresponding (S)-configurated saturated derivatives 2 , 4 , 6 , 8 , 10 and 12 , respectively. The highest enantiomeric excess revealed to be present in the saturated product 12 (32,7%, S) derived from the (Z)-configurated methyl ketone 11 (see Scheme 3 and Table 1). The reduction of the (E)-configurated starting materials led mainly to racemic products. A saturated product having the (R)-configuration with a rather weak enantiomeric excess (5.9%) has been obtained starting from the (E)-configurated methyl ketone 23 (see Scheme 5 and Table 2). The allylic alcohols 16 and 24 have been reduced to the saturated racemic derivative 17 .     

Reactions of 5-aryl-4-acyl-1-(4-hydroxyphenyl)-3-hydroxy-3-pyrrolin-2-ones with arylamines

The reaction of 5-(4-chlorophenyl)-4-benzoyl-1-(4-hydroxyphenyl)-3-hydroxy-3-pyrrolin-2-one with aromatic amines affords the corresponding 3-arylamino derivatives, and the reactions of 5-aryl-4-acetyl-1-(4-hydroxyphenyl)-3-hydroxy-3-pyrrolin-2-ones with p-toluidine yield 5-aryl-4-(1-p-tolylamino)ethylene-1-(4-hydroxyphenyl)pyrrolidin-2,3-diones.     

4-Substituted-3-alkyl-3,4-dihydro-2H-1,3-benzoxazin-2-ones II (1,2). Solvolytic transformations of urea and thiourea derivatives into 1-alkyldihydro-6-(2-hydroxyaryl)-1,3,5-triazine-2,4-(1H,3H) diones

A series of 3,4-Dihydro-2-oxo-(3-substituted-2H-1,3-benzoxazin-4-yl)ureas (II, Table I) and 3,4-dihydro-2-oxo-(3-substituted-2H-1,3-benzoxazin-4-yl)thioureas (Table II) was prepared by treating 3,4-dihydro-4-hydroxy-3-substituted-2H-1,3-benzoxazin-2-ones with ureas and thioureas, respectively. In the presence of alcoholic alkali these compounds underwent transacylation to dihydro-6-(2-hydroxyaryl)-1,3,5-triazine-2,4-(1H,2H)diones (Table III) and their 4-thio analogues (Table IV).     

Studies in organic mass spectrometry. Part 15 [1]. Electron ionization mass spectra of some 5-nitro-3-thiophenecarboxanilides

The study of the electron ionization mass spectra of 5-nitro-3-thiophenecarboxanilides 1-24 has shown peculiar effects induced by the 5-nitro group on the fragmentation of molecular ions M and the thenoyl cation a (Scheme 1). A comparison of the abundances of the important fragment ions for 5-nitro-3-thiophene-carboxanilides with those of the corresponding 3-thiophenecarboxanilides shows that the extent of C-N amide bond cleavage decreases in the former series as a consequence of the increased bond strength. The produced ion a does not eliminate carbon monoxide as 2- and 3-thenoyl cations usually do. Again this behaviour depends on the electronic effects of the nitro group which strongly destabilizes the 5-nitro-3-thienyl cation and consequently strengthens the carbon-3 carbonyl carbon bond. Recalling the behavior of the previously studied 2- and 3-thiophenecarboxanilides most of the 2′-substituted 5-nitro-3-thiophenecarboxanilides give loss of the ‘ortho’ substituent of the phenyl ring furnishing the cyclic ion g(Scheme 2). In the instance of 2′-alkyl substituted derivatives the formation of abundant ions h' by loss of 5-nitrothenoyl radical from M (Scheme 3) was observed, thus confirming the occurrence of a cryptic ‘ortho’ effect. The results are also discussed in relation to those obtained on some related benzoylanilides.     

Complexation of the 2, 4, 6‐Triallyloxy‐1, 3, 5‐triazine with Copper(I,II) Chlorides. Syntheses and Crystal Structures of [CuCl2·2C3N3(OC3H5)3], [Cu7Cl8·2C3N3(OC3H5)3], and [Cu8Cl8·2C3N3(OC3H5)3]·2C2H5OH

Interaction of copper(II) chloride with 2, 4, 6‐triallyloxy‐1, 3, 5‐triazine leads to formation of copper(II) complex [CuCl₂·2C₃N₃(OC₃H₅)₃] ( I ). Electrochemical reduction of I produces the mixed‐valence Cu^{I, II} π, σ‐complex of [Cu₇Cl₈·2C₃N₃(OC₃H₅)₃] ( II ). Final reduction produces [Cu₈Cl₈·2C₃N₃(OC₃H₅)₃]·2C₂H₅OH copper(I) π‐complex ( III ). Low‐temperature X‐ray structure investigation of all three compounds has been performed: I : space group P1¯, a = 8.9565(6), b = 9.0114(6), c = 9.7291(7) Å, α = 64.873(7), β = 80.661(6), γ = 89.131(6)°, V = 700.2(2) ų, Z = 1, R = 0.0302 for 2893 reflections. II : space group P1¯, a = 11.698(2), b = 11.162(1), c = 8.106(1) Å, α = 93.635(9), β = 84.24(1), γ = 89.395(8)°, V = 962.0(5) ų, Z = 1, R = 0.0465 for 6111 reflections. III : space group P1¯, a = 8.7853(9), b = 10.3602(9), c = 12.851(1) Å, α = 99.351(8), β = 105.516(9), γ = 89.395(8), V = 1111.4(4) ų, Z = 1, R = 0.0454 for 4470 reflections. Structure of I contains isolated [CuCl₂·2C₃N₃(OC₃H₅)₃] units. The isolated fragment of I fulfils in the structure of II bridging function connecting two hexagonal prismatic‐like cores Cu₆Cl₆, whereas isolated Cu₆Cl₆(CuCl)₂ prismatic derivative appears in III . Coordination behaviour of the 2, 4, 6‐triallyloxy‐1, 3, 5‐triazine moiety is different in all the compounds. In I ligand moiety binds to the only copper(II) atom through the nitrogen atom of the triazine ring. In II ligand is coordinated to the Cu^II‐atom through the N atom and to two Cu^I ones through the two allylic groups. In III all allylic groups and nitrogen atom are coordinated by four metal centers. The presence of three allyl arms promotes an acting in II and III structures the bridging function of the ligand moiety. On the other hand, space separation of allyl groups enables a formation of large complicated inorganic clusters.     

Pyrazolo [1,5-a]indole. 10. Mitteilung über metallogranische reaktionen und folgeprodukte

Pyrazolo[1,5- a ]indoles Treatment of 1-(2-heteroaroyl or aroyl-phenyl)-pyrazoles ( 3 ) with potassium hydroxide in 95% ethanol or with sodium ethanolate in ethanol produces a novel ring closure to new 4-hydroxy-4-(4-heteroaryl or aryl)-4H-pyrazolo [1,5-a]indoles 5 and 6 (Table 1). A 2, 3, or 4-pyridyl at position 4 is easily reduced yielding the 4-(2, 3, or 4-piperidyl)-derivatives 7 and 8 (Table 2). Water is split off from these piperidyl-derivatives 7 or 8 to give the piperidylidene derivatives 9 or 10 (Table 3) which may be considered as heterocyclic analogues to known tricyclic psychopharmaceuticals with antidepressant or neuroleptic activities.     

Über die Umsetzung von 1-Phenylpyrazol mit Äthylmagnesiumbromid. 8. Mitteilung über Grignard-Reaktionen [1]

In contrast to butyllithium, ethylmagnesium-bromide reacts with 1-phenyl-pyrazole exclusively by deprotonation, at the ortho position of the phenyl-ring. With nitriles the intermediate 2-(1-pyrazolyl)-phenylmagnesiumbromide gave good to excellent yields of 1-(2-aroyl or 2-hetaroyl-phenyl)-pyrazoles (Table 1, compounds 5a – 5i ); with ketones the corresponding methanol derivatives (Table 2, compounds 6a – 6c ) were found, whilst CO₂ yielded the corresponding 1-(2-carboxyphenyl)-pyrazole ( 3 ). Surprisingly enough, 1-(o-bromo-phenyl)-pyrazole and magnesium did not yield a single product, but a mixture of 3 compounds, which on reaction with 4-benzoylpyridine gave the three alcohols 19 , 20 and 21 .     

Ring-transformation reactions of 5-hydroxy-2-oxabicyclo[3.2.0]-heptan-4-ones and 5-hydroxy-2-oxabicyclo[3.2.0]hept-6-en-4-ones

Dehydrochlorination of chlorinated 5-hydroxy-2-oxabicyclo[3.2.0]heptan-4-ones, 3a-c, which were obtained from the photo[2+2]cycloadditions between 4-hydroxy-3(2H)-furanone 1 and chloroethylenes, with triethylamine gave 2-ethenyl-3(2H)-furanones 4a,b or 2-(2-cyanoethyl)-3(2H)-furanone 4c. 2-Oxa-bicyclo[3.2.0]hept-6-en-4-ones 7 being [2+2]cycloadducts between 1 and acetylenes gave 2,3-dihydro-3-oxooxepin derivatives 8 by electrocyclic rearrangement.     

Alkyl- and arylamination of 3-hydroxy-4-carbethoxy-5-methylthiophene

N-Alkylaminothiophene derivatives were obtained by the reaction of 3-hydroxy-4-carbethoxy-5-methylthiophene with alkylammonium acetates, while N-arylaminothiophene derivatives were obtained by the reaction of the same thiophene derivative with aromatic amines in the presence of catalytic amounts of iodine.Translated from Khimiya Geterotsilicheskikh Soedinenii, No. 12, pp. 1602–1604, December, 1970.     

Selective method for the preparation of isomeric N-alkyl and N-aryl-3(5)-amino-5(3)-hydroxy-1H-pyrazole-1-carboxamides

As part of a program to develop novel mechanism based skeletal muscle relaxants we identified 5-amino-3-hydroxy-1H-pyrazole-1-carboxamide (1) as a potential structural lead. This highly functionalized pyrazole was prepared via a published procedure [1] (Scheme 1, R¹ = R¹ = H), which utilized 3,5-dimethyl-1H-pyrazole-1-carboxamide as an aminocarbonyl transfer reagent, to give with cyanoacethydrazide the semicarbazide intermediate 6 . Base catalyzed cyclization of 6 afforded the initial lead compound. This reaction scheme was extended to the synthesis of additional 4-alkyl- and 4-aryl-5-amino-3-hydroxy-1H-pyrazole-1-carboxamides (Table 1).     

Synthesis of Some New Heteroylhydrazono‐1,3‐thiazolidin‐4‐ones

A series of (Z)‐methyl‐2‐[(Z)‐3‐substituted‐4‐oxo‐2‐(2‐picolinoyl‐/thiophene‐2‐carbonyl)‐hydrazonothiazolidin‐5‐ylidene]acetates were synthesized by condensation N‐substituted‐(2‐picolinoyl‐, thiophene‐2‐carbonyl)hydrazinecarbothioamides with dimethylacetylenedicarboxylate. The structure of thiazolidin‐4‐one derivatives has been confirmed unambiguously by single crystal X‐ray crystallography.     

Abkömmlinge der 3-Chinolincarbonsäure mit Sauerstoffsubstitution in Stellung 4, 5 and 8: Synthese,Reaktionen, NMR.-Studien

Derivatives of 3-Quinolinecarboxylic Acid with Oxygen Substitution in Positions 4, 5 and 8: Synthesis, Reactions, NMR. Studies Starting from either 1, 4-dibenzyloxybenzene (7) or 2, 5-dimethoxyaniline ( 16 ), synthetic routes have been developed to benzenoid and quinoid derivatives of 4-oxo-1, 4-dihydro-3-quinolinecarboxylic acid with O-bearing substituents in the positions 5 and 8 (compounds 12 - 15 , 19 , 20 , 23 , and 24 ). With the 1-ethyl-4, 5, 8 trioxo acid 14 as a dienophile, a series of linear tricyclic diene adducts ( 29 - 32 ) has been prepared, the structures of which were further modified by aromatization, reduction or dehydrogenation (compounds 33 - 40 ). A series of benzenoid and quinoid compounds with an additional substituent in position 6 or 7 (Table 1) has been derived mainly from the quinone 14 , primarily by addition of nucleophiles and eventually subsequent steps, and by aromatic electrophilic substitution of the 1-ethyl-5, 8-dimethoxy acid 23 . The substitution pattern of some of these compounds has been elucidated by detailed ¹³C-NMR. studies (Table 2) and/or nuclear Overhauser-effect studies (Table 3). Correlations, based essentially on chemical arguments, allowed to define the structures of most of the residual new compounds (Table 4).     

Synthesis of aldehyde and carboxylic acid derivatives from 2-hydroxymethyl-3-hydroxy-4H-pyran-4-one (α-hydroxymaltol)

α-Hydroxymaltol (2-hydroxymethyl-3-hydroxy-4H-pyran-4-one) ( 1 ) has been converted to the 3-O-methyl ether 2 and 3-O-p-nitrobenzyl ether 4 by standard methods. The ethers 2 and 4 have been oxidized by barium manganate to the corresponding aldehydes, 3 and 5 , in 91 and 77% yields respectively. Long-term reaction of 5 with hydrogen bromide in acetic acid gives 3-hydroxy-4H-pyran-4-one-2-carboxaldehyde ( 6 ). The aldehyde 3 is readily oxidized by short-term reaction with silver oxide to the corresponding acid 7 .     

Photolyse von 3-Methyl-2, 1-benzisoxazol (3-Methylanthranil) und 2-Azido-acetophenon in Gegenwart von Schwefelsäure und Benzolderivaten

Photolysis of 3-Methyl-2, 1-benzisoxazole (3-Methylanthranil) and 2-Azido-acetophenone in the Presence of Sulfuric Acid and Benzene Derivatives Irradiation of 3-methylanthranil ( 1 ) in acetonitrile in the presence of sulfuric acid and benzene, toluene, p-xylene, mesitylene or anisole with a mercury high-pressure lamp through a pyrex filter yields beside varying amounts of 2-amino-acetophenone ( 3 ) and 2-amino-5-hydroxy- ( 4a ) and 2-amino-3-hydroxy-acetophenone ( 4b ) the corresponding diphenylamine derivatives 5 (see Table 1). In the case of toluene and anisole mixtures of the corresponding ortho- and para-substituted isomers ( 5b, 5d or 5g, 5i respectively), but no meta-substituted isomers ( 5c or 5h ) are obtained. In addition to these products, the irradiation of 1 in the presence of anisole yields also 2-amino-5-(4′-methoxyphenyl)-acetophenone ( 7 ), 2-amino-3-(4′-methoxyphenyl)-acetophenone ( 8 ) and 2-methoxy-9-methyl-acridine ( 6 ; see Scheme 1). The latter product is also formed thermally by acid catalysis from the diphenylamine derivative 5i . Irradiation of 2-azido-acetophenone ( 2 ) in acetonitrile solution in the presence of sulfuric acid and benzene leads to the formation of 1, 3, 4a, 4b, 5a and 9 (see Table 2). Compounds 3, 4a, 4b and 5a are also obtained after acid catalyzed decomposition of 2 in the presence of benzene. Thus, it is concluded that irradiation of 1 or 2 in the presence of sulfuric acid yields 2-acetyl-phenylnitrenium ions 10 in the singlet ground state which will undergo electrophilic substitution of the aromatic compounds, perhaps via the π-complex 11 (see Scheme 2).     

Synthese von (±)-α-Chamigren. Vorläufige Mitteilung

Synthesis of (±)-α-Chamigrene Cis- and trans-β-ionol (cis and trans- 1 ) underwent acid catalysed dehydration to a mixture of the tetraenes 2–5 in 70–80% yield (Table 1). Irradiation of this mixtures made the 6-(Z), 8-(Z)-isomer 5 accessible (columns 3 and 4 in Table 1). Pyrolysis of the different mixtures at 170° showed, that both isomers, 3 and 5 respectively undergo electrocyclization to dehydrochamigrene ( 6 ). The latter was reduced to α-chamigrene ( 7 ) by hydrogen on Lindlar catalyst.     

Synthesis,characterization, and antimicrobial activities of two mononuclear metal(II) complexes with (Z)-3-hydroxy-4-(3-hydroxy-3-phenylacryloyl)phenyl benzoate

Two mononuclear complexes with a β-diketone ligand (Z)-3-hydroxy-4-(3-hydroxy-3-phenylacryloyl)phenyl benzoate (L), [CoL₂(CH₃CH₂OH)₂] (1), and [MnL₂(CH₃CH₂OH)₂] (2) were prepared. Both complexes were characterized by X-ray crystallography, confirming that the central metal(II) are coordinated by four oxygens from two L and two oxygens from two ethanols. Both complexes were assayed for in vitro antibacterial (Bacillus subtilis, Staphylococcus aureus, Streptococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, and Enterobacter cloacae) activities and showed better antimicrobial activity against Gram positive strains than Gram negative strains.     

Synthesis and reactions of 3-aroyl derivatives of 4-hydroxy-2-quinolones and 4-hydroxycoumarin

3-Aroyl-4-hydroxy-2-quinolones 4 and 11 can be synthesized starting with 1 or 9 via Fries rearrangement of the corresponding esters 3 and 10 , catalyzed by potassium cyanide and 18-crown-6. A one pot procedure is presented in which the esters do not need to be isolated. Reduction of the aryl ketones 4 and 11 with zinc dust leads to the benzyl derivatives 5 and 12 . Reaction of the aryl ketones 4 and 11 with hydroxylamine and subsequent heating of the crude product leads via thermal Beckmann rearrangement and dehydration to oxazoloquinolones 7 and 14 . 2-Aroyloxypyrido[1,2-a]pyrimidin-4-ones 17 and 20 could not be converted to the corresponding ketones by Fries rearrangement.     

Furopyridines. VIII. Molecular structure and two-dimensional NMR spectral assignment of 2,14-dimethyl-8aβ-hydroxy-7,10-dioxo-5β,6β-(propano)-6α,8α-(ethanoimino)-trans-perhydroisoquinoline

This paper reports the two-dimensional nmr spectral assignment and the X-ray structural determination of 2,14-dimethyl-8β-hydroxy-7,10-dioxo-5β,6β-(propano)-6α,8α-(ethanoimino)-trans-perhydroisoquinoline V which was obtained from 7,10-dimethyl-2β-hydroxy-14-oxo-2,3-(methanoiminoethano)-3β,4β-(propano)-3,4,5,6,7,8-hexahydro-2H-pyrano[2,3-c]pyridine IV by isomerization with hydrochloric acid. Both the compounds IV and V afforded the same dimethiodide IV -2MeI, while the configurational isomer 2,14-dimethyl-8aβ-hydroxy-7,10-dioxo-5α,6β-(propano)-6α,8α-(ethanoimino)-trans-perhydroisoquinoline III gave monomethiodide III -Mel. The structures of these methiodides were also confirmed by X-ray analysis.