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In the present work, free-cutting aluminum alloy AA6026 with 1.1 wt.% bismuth addition was fabricated by different melt preparation methods in order to investigate whether the melt preparation route affects the solidification sequence and thus has an influence on the machinability of the alloy. All experiments were designed to simulate variable industrial conditions: addition of bismuth in an induction melting furnace, addition of bismuth in an electric resistance holding furnace, addition of bismuth together with grain refiner, effect of holding time and melt temperature before casting. Detailed thermodynamic analyses (DSC, Thermo-Calc) and microstructural characterization (SEM-EDS, XRD) have been performed to explain the solidification sequence, microstructure development and especially formation of the intermetallic Mg3Bi2 phase.

A series of alkyl l-heteroaryl-1H-1,2,3-triazole-4-carboxylates 6a-u were synthesised in four steps from methyl (Z)-2-benzyloxycarbonylarmino-3-(dimethylamino)prop-2-enoate (1) and heterocyclic amines 2a-s. Triazoles 6a-o were tested against antimycobacterial activity. For the most active compound, n-pentyl 1-(6-phenylpyridazin-3-yl)-1H-1,2,3-triazole-4-carboxylate (6n), minimum inhibitory concentration 3.13 μg/ml was determined.

Reactions of 3-[(E)-(dimethylamino)methylidene]-(+)-camphor and (1R,5S)-4-[(E)-(dimethylamino)methylidene]-1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-one with hydrazine derivatives were studied. Treatment of 3-[(E)-(dimethylamino)methylidene]-(+)-camphor with hydrazines afforded the corresponding fused pyrazoles. Similarly, fused pyrazoles were obtained upon reaction of (1R,5S)-4-[(E)-(dimethylamino)methylidene]-1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-one with ortho-unsubstituted phenylhydrazines, while reactions with ortho-substituted phenylhydrazines and with hydrazine hydrochloride resulted in ‘ring switching’ type of transformation to furnish 2-aryl-4-[(1S,3R)-3-hydroxy-2,2,3-trimethylcyclopentyl]-1,2-dihydro-3H-pyrazol-3-ones.

Various (1R,5S)-4-[(E)-alkylidene]-1,8,8-trimethyl-2-oxabicyclo[3.2. 1]octan-3-ones were prepared, stereoselectively, via coupling of (1R,5S)-4-[(E)-(dimethylamino)methylidene]-1,8,8-tri-methyl-2-oxabicyclo[3.2.1]octan-3-one with Grignard reagents, potassium cyanide, and 2-methyl-lH-indole.

N-Substituted (1R,5S)-4-aminomethylidene-1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-ones were prepared in three steps from (1R)-(+)-camphor via coupling of (1R,4E,5S)-3-[(dimethylamino)methylidene]-1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-one with primary amines. N,N′-Bis-{[(1R,5S)-1,8,8-trimethyl-3-oxo-2-oxabicyclo[3.2.1]oct-4-ylidene]methyl}benzene-1,2-diamine was used as the ligand in the preparation of the corresponding coordination compounds with palladium(II), copper(II) and nickel(II). The structures were determined by 2D NMR techniques, NOESY spectroscopy and X–ray diffraction.

Keywords Reactions of 1-cyano-4-oxo-4H-quinolizine-3-diazonium tetrafluoroborate (1a) and 4-oxo-4Hpyridino[ 1,2-a]pyrimidine-3-diazonium tetrafluoroborate (1b) with aliphatic amines 2a - g were studied. Treatment of heteroaryldiazonium salts 1 with secondary amines 2a - d afforded the corresponding N-alkyl-N’-heteroaryltriazenes 3a - h in high yields. On the other hand, reactions of 1a with aliphatic primary amines 2e - g resulted in an unexpected rearrangements into the corresponding picolinic acid N-alkylcarboxamides 4a - c.

Reactions of ethyl 3-[(E)-(dimethylamino)methylidene]pyruvate (3) and 3-[(dimethylamino)methyl-idene]-2-oxosuccinate (4) with hydrazine monohydrochloride (5a) and (hetero)arylhydrazines (5b-i) afforded, regioselectively, 1-substituted ethyl 1H-pyrazole-5-carboxylates 9a-f and diethyl 1H-pyrazole-3,4-dicarboxylates, 11a-i, respectively. Upon treatment of 3 with pyridazinylhydrazines 5d-f, the stable intermediates, 1-substituted ethyl 4,5-dihydro-5-hydroxy-1H-pyrazole-5-carboxylates 8d-f, were isolated. Treatment of compounds 8d-f in acetic acid under reflux furnished the pyrazoles 9d-f. On the other hand, reaction of 3 with N,N′-dimethylhydrazine (51) gave ethyl 1-methyl-1H-pyrazole-3-carboxylate (14). The structures of compounds 3, 4, 14 were determined by nmr (noesy and hmbc techniques), while the structures of compounds 8f, 9f, and 11e, f were determined by X-ray diffraction.

Cycloadditions of various 1,3-dipoles to methyl (S)-1-tert-butoxycarbonyl-3-[(E)-cyanomethylidene]-2-pyrrolidinone-5-carboxylate (9) were studied. Reactions of 9 with diazomethane (10) and 2,4,6-trimethoxy-benzonitrile oxide (11), carried out under neutral conditions, gave the corresponding optically active spiro compounds 16-18 with low diastereoselectivity (20-30% diastereomeric excess). On the other hand, reactions of 9 with nitrile oxide 11 and nitrile imines 14, 15, carried out in the presence of a base, afforded racemic pyrazolo and isoxazolo fused 2-pyrrolidinones 21-23 in 82-86% diastereomeric excess. Optically active dipolarophile 9 was isomerized in the presence of basic alumina to give methyl (RS)-1-tert-butoxy-carbonyl-3-cyanomethyl-1,2-dihydro-2-oxo-5H-pyrrole-5-carboxylate (19). Treatment of the racemic dipolarophile 19 with dipoles 11 and 14, afforded fused 2-pyrrolidinones 23 and 21. These observations support compound 19 as the key-intermediate in the formation of racemic cycloadducts 21-23.

(1R,3R,4R)-3-(1,2,4-Triazolo[4,3-x]azin-3-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones were prepared in 68–94% d.e. in three steps from (1R)-(+)-camphor via coupling of (1R,4R)-3-[(E)-(dimethylamino)methylidene]-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one with hydrazinoazines followed by oxidative cyclisation of the intermediate hydrazones with methanolic bromine. The structures were determined by 2D NMR techniques and NOESY spectroscopy as well as by X-ray diffraction.

3-Substituted 5-[(Z)-heteroarylmethylidene]imidazolidine-2,4-dione and 5-[(Z)-heteroarylmethylidene]- 2-thiooxoimidazolidin-4-one derivatives were prepared stereoselectively by coupling of 5-(dimethylamino)methylidene substituted hydantoin and thiohydantoin derivatives with carbocyclic and heterocyclic C-nucleophiles.Configuration around the exocyclic C=C double bond was determined by NMR, using NOESY and 2D HMBC techniques.

Dedicated to Professor Emeritus Miha Tisler on the occasion of his 75th birthday Treatment of methyl (S)-5-[(E)-(dimethylamino)methylidene]-2-oxotetrahydrofuran-5-carboxylate (2) with potassium cyanide in acetic acid gave (S)-5-[(E)-cyanomethylidene]-2-oxotetrahydrofuran-5-car-boxylate (3), which was used as chiral dipolarophile in 1,3-dipolar cycloadditions. Reactions of 3 with diazomethane (4) and nitrile oxides 5a-c afforded spirolactones 6–8 in 24-34% diastereomeric excess, while with diazomethane (4) in the presence of triethylamine, methyl 3-cyanomethyl-2-methoxyfuran-5-carboxylate (12) was obtained.

Methyl (Z)-2-((tert-butoxycarbonyl)amino)-3-(dimethylamino)propenoate (3) was prepared in 2 steps from glycine methyl ester hydrochloride (1). Acid catalysed reactions of 3 with various alkyl-, aryl-, and heteroarylamines 4a-g, performed at 20-80 °C, proceeded by substitution of the dimethylamino group giving the corresponding substitution products, 3-N-substituted methyl (Z)-2-((tert-butoxycarbonyl)-amino)amino)propenoates 5a-g. Treatment of 3 with ambident 1,3- nucleophiles, such as 2-pyridineacetonitrile (6), 2-aminothiazole (4d), 2-aminopyridine (4f), and 4-hydroxy-6-methyl-2H-pyran-3-one (7) in acetic acid at 85-120 °C afforded fused pyridones 8 and 12, pyrimidones 9 and 10 and pyranones 11 and 13.

Some new aplysinopsin analogues were prepared by a simple coupling of N , N -(dimethylamino)methylidene substituted hydantoin, thiohydantoin, and thiazolone derivatives, with indole derivatives. Configuration around the exocyclic CC double bond was determined on the basis of long-range heteronuclear coupling constants using 2D HMBC correlation technique.

Alkyl (Z)-2-[(E)-2-ethoxycarbonyl-2-(2-pyridinyl)ethenyl]amino-3-dimethylaminopropenoates 7 and 8 were prepared from ethyl 2-pyridinylacetate (1) in two steps. Substitution of the dimethylamino group with alkyl-, aryl-, or heteroarylamines afforded the corresponding β-alkyl- 22–24, β-aryl- 25–35, and β-herteroaryl-amino-α,β-didehydro-α-amino acid 36 and 37 derivatives, intermediates for further preparation of various heterocyclic systems. The orientation around both double bonds were determined by various nmr techniques.

Ethyl (Z)-2-(2,3-dihydro-1,3-dioxo-1H-isoindol-2-yl)-3-(dimethylamino)propenoate was prepared in one step from ethyl (2,3-dihydro-1,3-dioxo-1H-isoindol-2-yl)acetate and bis(dimethylamino)-tert-butoxymethane and treated with various amines and hydrazines to afford the corresponding amino substituted products. Reactions of the titled compound with N,N'-, C,N-, and C,O'-ambident nucleophiles in refluxing acetic acid furnished the corresponding fused pyrimidinones, quinolizinones, and pyranones.

By catalytic hydrogenation of 3-(benzyloxycarbonyl)amino-4H-pyrido[1,2-a]pyridin-4-ones 28 and 29, and azino[1,2-x]pyrimidin-4-ones 32–35, 41, and 42, partial saturation of the heterocyclic systems and removal of the benzyloxycarbonyl moiety was observed to give 3-amino-6,7,8,9-tetrahydro-4H-pyrido[1,2 a]pyridin-4-ones 30 and 31, and 3-amino-6,7,8,9-tetrahydro-4H-azino[1,2-x]pyrimidin-4-ones 36–39, 43, and 44 in high yields. The methods represent a simple two step synthesis, starting from heterocyclic α-amino compounds and methyl (Z)-2-(benzyloxycarbonyl)amino-3-dimethylaminopropenoate followed by catalytic hydrogenation.

The 1-substituted 3-amino-4H-quinolizin-4-ones 13, available in two steps from 10 and methyl (Z)-2-benzyloxycarbonylamino-3-(dimethylamino)propenoate (11), were diazotized to give the stable diazonium tetrafluoroborates 7a and 7b. Heating of these diazonium salts in alcohols gave mixtures of 3-unsubstituted quinolizine derivatives 8a and 8b and the alkyl indolizine-3-carboxylates 9a−h. The ratio of the two types of products 8 and 9 was dependent on the type of alcohol employed. Thus, treatment of 7a or 7b with 2-propanol predominantly resulted in the 3-unsubstituted quinolizinones 8, while treatment of 7a or 7b with primary alcohols gave the indolizine-3-carboxylates 9 as the major products in most cases. The transformation of the 4-oxoquinolizine-3-diazonium tetrafluoroborates 7a and 7b into the alkyl indolizine-3-carboxylates 9a−h represents the first example of a Wolff rearrangement in the fused cyclic α-diazoamide series.

Some new aplysinopsin analogues were prepared by a simple coupling of N , N -(dimethylamino)methylidene substituted hydantoin, thiohydantoin, and thiazolone derivatives, with indole derivatives. Configuration around the exocyclic CC double bond was determined on the basis of long-range heteronuclear coupling constants using 2D HMBC correlation technique.

Dedicated to Professor Emeritus Miha Tisler on the occasion of his 75th birthday Treatment of methyl (S)-5-[(E)-(dimethylamino)methylidene]-2-oxotetrahydrofuran-5-carboxylate (2) with potassium cyanide in acetic acid gave (S)-5-[(E)-cyanomethylidene]-2-oxotetrahydrofuran-5-car-boxylate (3), which was used as chiral dipolarophile in 1,3-dipolar cycloadditions. Reactions of 3 with diazomethane (4) and nitrile oxides 5a-c afforded spirolactones 6–8 in 24-34% diastereomeric excess, while with diazomethane (4) in the presence of triethylamine, methyl 3-cyanomethyl-2-methoxyfuran-5-carboxylate (12) was obtained.

Ethyl (Z)-2-(2,3-dihydro-1,3-dioxo-1H-isoindol-2-yl)-3-(dimethylamino)propenoate was prepared in one step from ethyl (2,3-dihydro-1,3-dioxo-1H-isoindol-2-yl)acetate and bis(dimethylamino)-tert-butoxymethane and treated with various amines and hydrazines to afford the corresponding amino substituted products. Reactions of the titled compound with N,N'-, C,N-, and C,O'-ambident nucleophiles in refluxing acetic acid furnished the corresponding fused pyrimidinones, quinolizinones, and pyranones.

Thermal transformations of 3-azido-4H-quinolizin-4-ones 4a,b and 3-azido-4H-azino[1,2–x]pyrimidin-4-ones 4c,d, available from the corresponding heteroarylamines 2a–d, were studied. The reaction products were mostly dependent on the solvent. Thus, heating of 3-azido-1-cyano-4H-quinolizin-4-one (4a) in toluene afforded 2-(pyridin-2-yl)fumaronitrile 5a, whereas 3-amino-1-cyano-4H-quinolizin-4-one (8) was obtained on treatment of 4a in a mixture of toluene and trifluoroacetic anhydride. However, heating of 4a in acetic anhydride and in acetic acid resulted in a ring contraction to produce 3-(diacetylamino)indolizine-1-carbonitrile 6a and 3-(acetylamino)indolizine-1-carbonitrile 7a, respectively. Similarly, ring contractions took place on heating ethyl 3-azido-4-oxo-4H-quinolizin-1-carboxylate 4b and 3-azido-4H-azino[1,2–x]pyrimidin-4-ones 4c,d in acetic anhydride or acetic acid to produce the N-acetylated 3-aminoindolizine derivatives 6b, 7b and 3-aminoimidazo[1,2–x]azine derivatives 6c,d in 30–89% yields. The structures of compounds 5–8 were determined by NMR spectroscopy and X-ray diffraction.

(S)-3-(Dimethylamino)methylidene-5-benzyltetramic acid derivatives 4a and 4b were prepared in three steps from N-protected (S)-3-phenylalanines la and 1b, respectively. Similarly, N-[N-(benzyloxycarbonyl)glycyl]glycine (1c) was transformed into the enaminone 4c. Acid-catalysed coupling of enaminones 4a-c with aliphatic, aromatic, and heteroaromatic primary amines 5-34 afforded the corresponding N(3')-substituted 3-aminomethylidenetetramic acid derivatives 35-64 in 29-96% yields.

A series of alkyl l-heteroaryl-1H-1,2,3-triazole-4-carboxylates 6a-u were synthesised in four steps from methyl (Z)-2-benzyloxycarbonylarmino-3-(dimethylamino)prop-2-enoate (1) and heterocyclic amines 2a-s. Triazoles 6a-o were tested against antimycobacterial activity. For the most active compound, n-pentyl 1-(6-phenylpyridazin-3-yl)-1H-1,2,3-triazole-4-carboxylate (6n), minimum inhibitory concentration 3.13 μg/ml was determined.

Various (1R,5S)-4-[(E)-alkylidene]-1,8,8-trimethyl-2-oxabicyclo[3.2. 1]octan-3-ones were prepared, stereoselectively, via coupling of (1R,5S)-4-[(E)-(dimethylamino)methylidene]-1,8,8-tri-methyl-2-oxabicyclo[3.2.1]octan-3-one with Grignard reagents, potassium cyanide, and 2-methyl-lH-indole.

Reactions of ethyl 3-[(E)-(dimethylamino)methylidene]pyruvate (3) and 3-[(dimethylamino)methyl-idene]-2-oxosuccinate (4) with hydrazine monohydrochloride (5a) and (hetero)arylhydrazines (5b-i) afforded, regioselectively, 1-substituted ethyl 1H-pyrazole-5-carboxylates 9a-f and diethyl 1H-pyrazole-3,4-dicarboxylates, 11a-i, respectively. Upon treatment of 3 with pyridazinylhydrazines 5d-f, the stable intermediates, 1-substituted ethyl 4,5-dihydro-5-hydroxy-1H-pyrazole-5-carboxylates 8d-f, were isolated. Treatment of compounds 8d-f in acetic acid under reflux furnished the pyrazoles 9d-f. On the other hand, reaction of 3 with N,N′-dimethylhydrazine (51) gave ethyl 1-methyl-1H-pyrazole-3-carboxylate (14). The structures of compounds 3, 4, 14 were determined by nmr (noesy and hmbc techniques), while the structures of compounds 8f, 9f, and 11e, f were determined by X-ray diffraction.

Cycloadditions of various 1,3-dipoles to methyl (S)-1-tert-butoxycarbonyl-3-[(E)-cyanomethylidene]-2-pyrrolidinone-5-carboxylate (9) were studied. Reactions of 9 with diazomethane (10) and 2,4,6-trimethoxy-benzonitrile oxide (11), carried out under neutral conditions, gave the corresponding optically active spiro compounds 16-18 with low diastereoselectivity (20-30% diastereomeric excess). On the other hand, reactions of 9 with nitrile oxide 11 and nitrile imines 14, 15, carried out in the presence of a base, afforded racemic pyrazolo and isoxazolo fused 2-pyrrolidinones 21-23 in 82-86% diastereomeric excess. Optically active dipolarophile 9 was isomerized in the presence of basic alumina to give methyl (RS)-1-tert-butoxy-carbonyl-3-cyanomethyl-1,2-dihydro-2-oxo-5H-pyrrole-5-carboxylate (19). Treatment of the racemic dipolarophile 19 with dipoles 11 and 14, afforded fused 2-pyrrolidinones 23 and 21. These observations support compound 19 as the key-intermediate in the formation of racemic cycloadducts 21-23.

By catalytic hydrogenation of 3-(benzyloxycarbonyl)amino-4H-pyrido[1,2-a]pyridin-4-ones 28 and 29, and azino[1,2-x]pyrimidin-4-ones 32–35, 41, and 42, partial saturation of the heterocyclic systems and removal of the benzyloxycarbonyl moiety was observed to give 3-amino-6,7,8,9-tetrahydro-4H-pyrido[1,2 a]pyridin-4-ones 30 and 31, and 3-amino-6,7,8,9-tetrahydro-4H-azino[1,2-x]pyrimidin-4-ones 36–39, 43, and 44 in high yields. The methods represent a simple two step synthesis, starting from heterocyclic α-amino compounds and methyl (Z)-2-(benzyloxycarbonyl)amino-3-dimethylaminopropenoate followed by catalytic hydrogenation.

Thermal transformations of 3-azido-4H-quinolizin-4-ones 4a,b and 3-azido-4H-azino[1,2–x]pyrimidin-4-ones 4c,d, available from the corresponding heteroarylamines 2a–d, were studied. The reaction products were mostly dependent on the solvent. Thus, heating of 3-azido-1-cyano-4H-quinolizin-4-one (4a) in toluene afforded 2-(pyridin-2-yl)fumaronitrile 5a, whereas 3-amino-1-cyano-4H-quinolizin-4-one (8) was obtained on treatment of 4a in a mixture of toluene and trifluoroacetic anhydride. However, heating of 4a in acetic anhydride and in acetic acid resulted in a ring contraction to produce 3-(diacetylamino)indolizine-1-carbonitrile 6a and 3-(acetylamino)indolizine-1-carbonitrile 7a, respectively. Similarly, ring contractions took place on heating ethyl 3-azido-4-oxo-4H-quinolizin-1-carboxylate 4b and 3-azido-4H-azino[1,2–x]pyrimidin-4-ones 4c,d in acetic anhydride or acetic acid to produce the N-acetylated 3-aminoindolizine derivatives 6b, 7b and 3-aminoimidazo[1,2–x]azine derivatives 6c,d in 30–89% yields. The structures of compounds 5–8 were determined by NMR spectroscopy and X-ray diffraction.

Methyl 2-benzoylamino-2-oxobutanoate (1) was transformed with aromatic amines (2a-d) into methyl 2-arylamino-2-(benzoylamino)but-2-enoates (3a-d) Cyclization of compounds (3a-c) in polyphosphoric acid affords a mixture ofoxazolo[4,5-c]quinoline derivatives (4a-c) and 1 -aryl-2-phenyl-5-methyl- 1H-imidazole-4-carboxylates (5a-c), while compound 3d gives a mixture of 9-bromo- (4d) and 7-bromooxazolo[4,5-c]quinoline derivative (4d').

Coupling of 1-cyano-4-oxo-4H-quinolizine- (2), 1-ethoxycarbonyl-4-oxo-4H-quinolizine- (3), and 4-oxo-4H-pyridino[1,2-b]pyrimidine-3-diazonium tetrafluoroborates (4) with 1,3-dicarbonyl compounds (la-i) afforded the corresponding hydrazones (5-7) in 55-96% yields. The orientation around the C=N double bond in unsymmetrically substituted hydrazones (7a,c) was determined by NMR (NOESY) spectrometry. Heating of hydrazones (5a,b-7a,b), derived from alkyl 4-chloro-3-oxobutanoates (1a,b), furnished 1-(1-substituted quinolizin-3-yl)- (8, 9) and 1-(pyridino[1,2-a]-pyrimidin-3-yl)-4-hydroxy-1H-pyrazole-3-carboxylates (10) in 87-96% yields.

(Z)-3-Benzoylamino-4-dimethylamino-2-oxo-3-butene (4), prepared from 1-benzoylamino-2-propanone (3) and N,N-dimethylformamide dimethyl acetal, was converted regioselectively by reaction with a series of hydrazines (5) into 1-substituted 4-benzoylamino-5-methyl-1H-pyrazoles (8). Reactions of 4 with primary amines (10) and with dimethylbarbituric acid (12) afforded the dimethylamine substitution products (11) and (13), respectively. Treatment of the butenone (13) with ammonia furnished tetrahydropyrido[2,3-d]pyrimidine derivative (14).

5-(2-Phenyl-1H-indol-3-ylmethylene)-2-thioxoimidazolidin-4-one (2) and its oxo derivatives as well as some novel 5-bromoaplysinopsin analogues were synthesized employing dimethylamine substitution in N,N-dimethyl-methylideneimidazolidinones (6).

The 1-substituted 3-amino-4H-quinolizin-4-ones 13, available in two steps from 10 and methyl (Z)-2-benzyloxycarbonylamino-3-(dimethylamino)propenoate (11), were diazotized to give the stable diazonium tetrafluoroborates 7a and 7b. Heating of these diazonium salts in alcohols gave mixtures of 3-unsubstituted quinolizine derivatives 8a and 8b and the alkyl indolizine-3-carboxylates 9a−h. The ratio of the two types of products 8 and 9 was dependent on the type of alcohol employed. Thus, treatment of 7a or 7b with 2-propanol predominantly resulted in the 3-unsubstituted quinolizinones 8, while treatment of 7a or 7b with primary alcohols gave the indolizine-3-carboxylates 9 as the major products in most cases. The transformation of the 4-oxoquinolizine-3-diazonium tetrafluoroborates 7a and 7b into the alkyl indolizine-3-carboxylates 9a−h represents the first example of a Wolff rearrangement in the fused cyclic α-diazoamide series.