Chinolizine und Indolizine,XIII. Acyl-2-hydroxy-4-chinolizinone

The reaction of 2-picolylketones (1 a, b) with reactive trichlorophenyl malonates (2 a–f) leads to 1-acyl-2-hydroxy-4-quinoliziones (3 a–i) which can be easily deacylated by boiling hydrochloric acid yielding 4-quinolizinones4 a–f. The 3-acetyl-2-hydroxy-4-quinolizinones6 and8 are obtained byKlosa-Ziegler acylation of4 a and7, respectively. The reaction of the acetyl compound3 a with acetic anhydride yields the 2-pyrone derivative9, whereas the propionyl derivative3 g yields the 4-pyrone10 under the same conditions. Nitration of3 e does not give the 1-nitro derivative12 but rather the 1,3-dinitro compound11.     

A silyl-α-cyclodextrin intermediate. Preparation and characterization of dodeca-t-butyldimethylsilyl-hexahydroxy-α-cyclodextrin

The title compound (II) was prepared by treating dry, purified α-cyclodextrin with 20 equivalents oft-butyldimethylsilyl chloride 20 hr at 110° in DMF/pyridine. Work-up of the product mixture gave 60%II, which was identified by¹H and¹³C NMR. Treatment ofII with Bu₄NF 6 hr in refluxing dry THF efficiently removed the protecting groups.     

Pyrindinchemie, 1. Mitt.: Über die Synthese des 3-Hydroxy-1-methyl-4-oxo-1,4-dihydropyrrolo[2′,3′:3,4]cyclopenta[1,2—b]pyridin-2-carbonsäureäthylesters (Ein Vertreter eines neuen heterocyclischen Ringsystems)

4 is synthesized starting from1 over the chloride3 and then cyclized byDieckmann condensation to the title compound8. The structure of4 is confirmed by chemical proof. By means of¹H-NMR-spectral analysis it could be determined that1 exists as internal salt (2a) of ethyl 5-hydroxy-7-oxo-7H-1-pyrindin-6-carboxylate.     

Über die Synthese von 1,3-Dihydro-3-(2-dimethylaminoäthyl)-1-(3-thienyl)-benzimidazol-2-onen

The synthesis of 1-(3-thienyl)-benzimidazol-2-ones (3 a and4), described in an earlier paper¹, has been further investigated. The Na-salt of3 a is converted to a benzimidazolone substituted in position 3 (3 b). Dehydrogenation of the thiophene nucleus of3 a with chloranil yields5 a, which undergoes substitution in position 3 with Cl(CH₂)₂N(CH₃)₂ to give5 b. Monochlorination of5 a yields5 c, the structure of which is confirmed by¹H-NMR-spectroscopy.5 d is obtained by reaction of the Na-salt of5 c with Cl(CH₂)₂N(CH₃)₂.      

Synthese,Kristallstruktur und Konformation vontrans-[2.2](1,2)Ferrocenophan und seinen 1-Hydroxyderivaten

Starting from1-(dimethylaminomethyl)-2-iodo-ferrocene (3) [2.2](1,2)ferrocenophane (2) was prepared in an 8-step synthesis with 17% overall yield. Both from the oxoderivative12 and the ferrocenophane2 puretrans-isomers (12b and2b, resp.) were obtained; the former (12b) was reduced to a separable mixture ofexo andendo 1-hydroxy-ferrocenophanes13a andb, resp. (～ 3:7), the configurations of which were assigned by the LIS-method. X-ray crystal structure analysis of2b revealed a centrosymmetrical chair conformation. From¹H- and¹³C-NMR spectra both for2b and for the hydroxyderivatives13 a rigidexo-exo chair conformation was deduced.     

Autoassembly of cage structures

Thed,l-(1a) andmeso-forms (1b) of α,α'-dihydroxy-α,α'-dimethyladipic acid, dilactone (3), diiminodilactone (4), and lactonolactam (5) were obtained by the reaction of acetonylacetone with KCN and HCl. The transformations of1 to the esters2, dilactone3 to la, and diiminodilactone4 to dilactone3 were studied. It was shown that3 can be readily obtained from la by thermolysis, acid catalysis, and DCC action as well as by acid catalyzed cyclization of2a, while dilactone3 can be obtained from1b and2b in negligible yield only under drastic conditions, obviously, due to the partial epimirization of themeso-forms. The mild thermolysis of1b leads totrans-lactonoacid (6), from which the ester7 has been obtained. The effective acid catalyzed cyclization of amides8 and9 to3, lactamoamide12 to5, and amide14 to model lactone13 was found. The NMR spectra of the products were studied, and a¹H NMR test was suggested for identification ofd,l- andmeso-forms1 and2. The stereochemistry of monolactones6, 7, 9, 10a, 10b, 11, and dilactone3 was established. The differences in the chemical behavior of α,α'-dihydroxyglutaric and adipic acids were explained by the significant reduction of the non-bonded interactions of the substituents in the corresponding monolactones during the transfer from 1,3- to 1,4-substituted systems.     

Chemie des 5,7-Dihydroxy-2H-thiopyrano[2,3-b]pyridin-4(3H)-ons

Hydrolysis of the 4-alkyliminothiopyrano[2,3-b]pyridinedioles (5) and 4-alkylaminothiopyrano[2,3-b]pyridones (6) resp. with 10% NaOH gives 5,7-dihydroxy-2H-thiopyrano[2,3-b]pyridine-4(3H)-one (7).7 can be obtained in better yield by reaction of 4-dimethylamino-2(1H)-pyridinethione (8) with bistrichlorphenylethylamlonate (2). Aminolysis of7 affords the two isomeric products5 and6. On treatment with hydrazines,7 reacts only to 4-hydrazonoderivatives5. By heating in bromobenzene5d is cyclisized to 1H-5,1,2,6-thiatriaza-acenaphthylen-7-ol (11). On methylation with methyljodide5,6 and7 furnish the 7-methoxyproducts13,14 and12. By heating in 20% NaOH7 is transformed into the 2-thioxo-3-pyridylmethylketone16 A and its tautomer, 2-mercapto-3-pyridylmethylketone16 B. The structures of5,6 and7 are discussed.     

Über cyclische Guanidin—Mesityloxid- und Guanidin—Phoron-Kondensate

The basic product synthesized byTraube andSchwarz from mesityl oxide and guanidine has not been 4.4.6-trimethyl-4.5-dihydro-2-pyrimidinamine (1), but a mixture containing the 4.4.6-trimethyl-3.4-dihydro-2(1H)-pyrimidinimine (resp. an isomeric pyrimidinamine)2 a (resp.2 b, 2 c) and the dimeric 4.4′-methylenedi[2(1H)-pyrimidinimine] (resp. an isomeric methylenedipyrimidinamine)3 a (resp.3 b, 2 c) and the dimerisation reaction were studied in a series of experiments. The product of the reaction of guanidine and phorone is not the guanidinopropylpyrimidine8 ⁴, but the 4.4′-spirobi[2(1H)-pyrimidinimine] (resp. a spirobipyrimidinamine)11 a (resp.11 b, 11 c). No determination was possible on the basis of NMR whether the condensation products of guanidine—in solutions ofDMSO-d₆—are pyrimidinimines (2 a, 3 a, 11 a) or pyrimidinamines (2 b resp.2 c, 3 b resp.3 c, 11 b resp.11 c) or mixtures of the isomeric compounds. The NMR-and mass spectra of2 a (resp.2 b, 2 c),3 a (resp.3 b, 3 c),11 a (resp.11 b, 11 c) and their derivates are discussed.     

Synthese von (5,10)-(7,8)-Bisepoxiden aus α- und β-4-Phenyl-1,2,4-triazolin-3,5-dion-Addukten von Vitamin D3 und Röntgenstrukturanalyse eines der Benzoylderivate

Oxidation of the α- and β-4-phenyl-1,2,4-triazolin-3,5-dione adducts of vitamin D₃ (2 and1) withMCPBA yields two diastereomeric mixtures of the (5,10)-(7,8)-dioxiranes3 a,3 b,3 c and4 a,4 b respectively. The corresponding benzoates5 a,5 b,6 a and6 b were prepared and the X-ray crystal structure of5 b was determined. This analysis proved5 b to be the (5R, 1 OS)-(7R, 8R)-dioxirane of the β-resp. (6S)-4-phenyl-1,2,4-triazolin-3,5-dione adduct1 of vitamin D₃.     

Über das 7-Methyl-4,5-diphenyl-4,4a,5,6,7,8,10,10a-octahydro-7,10a-methano-pyrimido[4,5—d][1,3]-diazocin-2,9(1H,3H)-dion

The condensation product (C₁₁H₁₂N₂O) _x synthesized byZigeuner andBrunetti ³ from urea and 4-phenyl-3-buten-2-one is a methanopyrimidodiazocinedione (7, title compound), which has the conformation formula7 K. The formulae7 and7K are constituted taking as a basis the 100 MHz-NMR-spectrum (with double resonance experiments) and the mass spectrum of7; two possible ways for the formation of7—genetic an ureylenchinazolinone—from urea and 4-phenyl-3-buten-2-one are suggested.     

Further studies on the taumerization of the hydrido (alkynyl) cluster Ru3Pt(μ-H) {μ4-ν2-C ≡ C1Bu} (CO)9(L2) to the vinylidene cluster Ru3Pt{μ4-ν2-C ≡ C(H)tBu} (CO)9(L2): X-ray structures of Ru3Pt(μ-H){μ4-ν2-C = C(H)tBu} (CO)9(L2); L2 = dppet,dppp, andS,S-dppb

The first order rate constants for the tautomerization of the hydrio(alkynyl) clusters Ru₃Pt(μ-H){μ₄-ν²-C ≡ C¹Bu}(CO)₉(L₂);1a: L₂ = dppe,1b; L₂ = dppet,1c; L₂ = dppp and1d; L₂ =S,S-dppb to the corresponding vinylidene clusters Ru₃Pt{μ₄-ν²-C = C(H)^tBu}(CO)₉(L₂)2 have been measured, and they follow the orser1d <1a <1b ～1c. The reactions involving1a and1d exhibit an inverse kinetic deuterium isotope effect. The structures of1b, 2b, 2c, and2d were determined by X-ray crystallography, and are compared with those of1a and2a which have been previously reported. Crystal data for1b, space groupPbca,a = 13.338(4) Å,b = 17.771(6) Å,c = 36.092(8) Å,Z = 8,R(R _w) = 0.059(0.058) for 2342 absorption corrected, observed data; for2b, space group P2₁/n,a = 10.566(2) Å,b = 20.234(5) Å,c = 20.270(3) Å,β = 96.11(1)°,Z = 4,R(R _w) = 0.043(0.053) for 5865 absorption corrected, observed data; for2c, space group P2₁/n,a = 14.211(5) Å,b = 19.534(2) Å,c = 15.870(2) Å,β = 100.81(2)°,Z = 4,R(R _w) = 0.055(0.031) for 6566 absorption corrected, observed data: for2d, space group P2₁2₁2₁,a = 12.309(4) Å,b = 19.047(6) Å,c = 19.206(4) Å,Z = 4,R(R _w) = 0.055(0.053) fpr 2151 absorption corrected, observed data. The fluxional behavior of1d and1e (which consists of two interconverting isomers) has been examined by variable temperature¹³C NMR spectroscopy and by³¹P EXSY.     

Darstellung und Struktur von Pyrazolyl-Kationen mit Polymethin- und Methan-Gerüst

The 4-pyrazoline-3-one1 reacts with 4-dimethylaminobenzaldehyde to yield the stable asymmetric cyanine dye2b which reacts with1 to give the colorless (aryl) (dipyrazolyl) methane3b. Using aldehydes with less cationstabilizing groups the polymethines2 are not isolated but only the methanes3. The structures of2b and3 are discussed by¹ H,¹³C and Hetero NMR spectra.     

Über Reaktionen mit Betainen, 18. Mitt. Über Betaine und ihre Beziehungen zu N-Yliden. Trifluoracetyl-N-methylide und ihre Beziehungen zu den entsprechenden Ammoniumbasen

The betaines1b–d were prepared⁴ by systematic variation of the alkyl groups and were reacted with trifluoroacetic acid anhydride (TFA) to give the diacyl-ylides2b,c. The betain1d andTFA afford the trifluoroacetate3d ⁵. The salts3b,c, which result from hydrolysis of2b,c as well as3d (X=I) can be transformed in 75 to 83% yield into the monoacyl-ylides4b–d with the help of silver oxide. Aqueous solutions of4a–d exhibit alkalinepH, which points to the formation of the corresponding ammonium bases. In the case of4b,c the bases5b,c could be isolated. It can be shown, that4b,c and5b,c, respectively, undergo a reversible addition or elimination of one mole wather with great ease.     

7,15-Diazadispiro[5.1.5.3]hexadecan und Derivate, 1. Mitt.: Darstellung der Grundkörper

As starting materials for theoretical and pharmacological studies 7,15-diazadispiro[5.1.5.3]hexadecane (1), its 14-imino-(2) and 14-oxo-derivative (3) were prepared. Reduction of bis-(1-cyanocyclohexyl)-amine (4) withLAH leads to a mixture of1 and2. For the exclusive preparation of1, 4 is treated with conc. H₂SO₄ to yield the corresponding 14,16-dioxohexadecane, which is reduced to1 withLAH. The preparation of3 is effected by acid hydrolysis of acetylated2.     

Stereochemie von α,ω-Diphenyl-alkan-α,ω-diolen

Reduction (both catalytically and with complex hydrides) of the diphenyl diketones1 (a, b, c andd withn=0, 2, 3 and 4) was investigated mainly with regard to the diastereomeric ratio of the diols2. For2 a and2 b exact results were obtained by NMR spectroscopy (without or with shift reagents) of the diol mixture (2 a) or after stereoselective cyclization to the cyclic ethers (3 b). AlsoGC andLLC were employed for the analysis of2 a (GC of the trimethylsilyl derivatives) and for the ethers3, resp. (GC for3 a and3 d;LLC for3 b and3 c). The reduction of1 a, 1 b (and in part1 c) proceeds with high stereoselectivity; themeso-diol preponderates in the case of2 a, therac.-diol for2 b and2 c; with increasingn the diastereomeric ratio approaches the statistical ratio of 1∶1. Preparations of the stereoisomeric diols (2 b, c andd via acetylenic precursors) and of the cyclic diphenyl ethers (by stereoselective cyclization and/or chromatographic separation;3 c and3 d for the first time) as well as the determination of their configurations are described. The latter was achieved by NMR and for the ethers3 also by hydrogenation of the corresponding heteroaromatics.     

Pyrindinchemie, 2. Mitt.: Über die Synthese des 5,6-Dihydro-2-pyrindin-7-ons

The reaction of cinchomeronic anhydride with diethyl malonate in acetic anhydride in the presence of triethylamine yields1, which is hydrogenated over Pd/C (10%) in dry benzene to2. The structures of1 and2 are confirmed by IR-and¹H-NMR-spectra.1 can be reduced to3 with Zn in acetic acid. Hydrolysis of3 yields4, which is easily decarboxylated to5. Methylation of5 with CH₂N₂ gives6. The¹H-NMR-spectrum of6 makes a definite structural assignment possible.6 undergoes a Dieckmann cyclisation to7, which forms8 on heating in water, and the title compound9 on heating in 4n-HCl.     

Chinolizine und Indolizine,XIV Umlagerungen von Heterocyclen,X Ringumwandlungen von 1-Acyl-2-hydroxy-4-chinolizinonen

By heating with ammonia or aniline 1-acyl-2-hydroxy-4-quinolizinones (1 a–e) are transformed to 4-hydroxy-5-(2-pyridyl)-2-pyridones (3 a–f), with4 a–d as minor sideproducts. The structure of the rearranged compound3 f was established by an independent synthesis starting with6 and7. The reaction of1 a, d with ethyl β-aminocrotonate (β-ACE) yields pyrono-quinolizinones8 a, b and pyronopyridones9 a, b as byproducts; the latter are obtained in high yield by reaction of3 a, b with β-ACE. The ringtransformation reaction cannot be extended to 1-methoxycarbonyl-quinolizinones, such as10; in this case 2-amino-4-quinolizinone11 is the main product of the reaction with ammonia.     

Pyrindinchemie, 3. Mitt.: Über die Synthese des 3-Hydroxy-1-methyl-4-oxo-1,4-dihydro-pyrrolo[2′,3′:3,4]cyclopenta[1,2-c]pyridin-2-carbonsäureäthylesters. Ein Vertreter eines neuen heterocyclischen Ringsystems

1 is synthesized by reaction of cinchomeronic anhydride with ethyl acetoacetate and triethylamine in acetic anhydride. Its structure is discussed by means of IR- and¹H-NMR-spectrum. By reaction of1 with SOCl₂ 3 is formed, which is converted with ethyl sarcosinate to4. The structure of4 is confirmed by chemical proof.Dieckmann cyclisation of4 gives the title compound7.     

Numerical modelling of inclusion-type complexes formed by chiral 18-crown-6 ethers bearing sugar moieties with enantiomers of phenylalanine methyl ester cations

The crystal structure of α-d-mannosido-benzo-18-crown-6·KSCN (1) was solved by X-ray single crystal diffractometry. C₂₈H₃₆O₁₀·KSCN is orthorhombic, space groupP2₁2₁2₁ withZ=4,a=8.035(4),b=9.960(2),c=38.83(2) Å,M _r =629.8,V=3103.6 ų,D _x =1.347 g cm^?3, μ(CuKα)=2.53 mm^?1, λ=1.54178 Å,F(000)=1324. FinalR=0.043 for 1139 unique observed reflections measured at room temperature. The potassium ion is surrounded by a nearly planar hexagon of oxygen atoms of the macrocyclic ring and lies on the plane formed by those atoms. Hexagonal pyramidal coordination is completed by the nitrogen atom of the thiocyanate anion. The SCN ion was found on the face of the macrocyclic ring opposite that for the chiral mannopyranoside moiety. The molecular structure of α-d-mannosido-18-crown-6 (2) and the structure of molecular complexes of2 and α-d-glucosido-benzo-18-crown-6 (3) were studied by molecular mechanics methods. The results suggest enthalpy driven selectivity of complexation of the phenylalanine methyl ester (4) by2 and both enthalpy and entropy effects in selective complexation of4 by3.     

Synthesis of 2,5-bis(piperidinomethyl)piperidine and 1,5-bis(aminomethyl)-3-azabicyclo[3.2.1]octanones

Schmidt reaction of mono- and bis-Mannich bases1 and2 c derived from cyclopentanone gave the corresponding basically substituted 2-piperidones3 and4, respectively. Reduction of the latter afforded5. DoubleMannich reaction of2 a–c with primary amines gave 3-azabicyclo[3.2.1]octanone derivatives6 a–e and7. The transamination of2 a was investigated.