Reactions with the Arylhydrazones of some α-cyanoketones

Ethereal diazomethane reacts with the arylhydrazones of mesoxalic acid dinitrile 1a–c and of ethyl α-cyanoglyoxalate 2b, d–g to yield the methylarylhydrazones 3a–c and 4a–e respectively. Treatment of 4b–e with phenylmagnesium bromide results in the formation of the imino derivatives 5a–d . Whereas 2a–g react with phenylhydrazine to yield the aminopyrazoles 8a–g , the hydrazides 10a, b are formed on treatment of 4c, e with hydrazine hydrate. 1a–c react with hydrazine hydrate and with phenylhydrazine to yield 3-amino-4-arylhydrazono-5-imino-2-pyrazoline derivatives 11a–f 11a, b react with acrylonitrile to yield 3-amino-1(β-cyanoethyl)-4-arylhydrazono-5-imino-2-pyrazoline derivatives 12a, b which can be readily cyclised to the pyrazolo[3,2-b]pyrimidine derivatives 13a, b by the action of hot acetic acid.     

Lewis‐acid catalysed ene reaction of electrondeficient aldehydes and ketones at unsaturated fatty acid derivatives

The SnCl₄ catalysed reaction of oleic acid ethyl ester (1) with glyoxylic acid ethyl ester (2) or mesoxalic acid diethyl ester (5) proceeds with good results yielding the corresponding 1:1‐adducts. Besides the ene adducts also δ‐lactones are formed by the reaction of (1) with (5) . The product yield shows a strong dependency on type and quantity of the Lewis‐acid used. A maximum yield was obtained with a stoichiometric amount of SnCl₄. In contrast to the thermal ene reaction about 75% of the yield was attained already during the first 30 min of the reaction.     

Photochemische Reaktionen von Pyrazolidon-(3)-betainen. IV. Photooxydation von Pyrazolidon-(3)-azomethiniminen

Photochemical Reactions of 3-Pyrazolidone Betains. IV. Photooxidation of 3-Pyrazolidone Azomethinimines Azomethinimines 1 , easily obtainable from 3-pyrazolidone and aldehydes, on dyesensitized photooxidation in methanol as a solvent undergo decomposition to nitrogen, methyl β-methoxypropionate 3 , methyl acrylate 4 and the corresponding aldehyde 2 . The formation of these products is interpreted by formation and decomposition of a cyclic peroxide 5 , produced by a 1,3-dipolar cycloaddition reaction between 1 and singlet oxygen. The photooxidation of 1 in acetonitrile produces: nitrogen, carbon dioxide, ethylene, β-propiolactone 9 , and the corresponding aldehyde 2 . The dye-sensitized photooxidation in methanol of the azomethinimines 16 , prepared from 3-pyrazolidone and ketones, gives the following products: nitrogen, methyl β-methoxypropionate 3 , methyl acrylate 4 , and the corresponding ketone, besides hydrazine and the corresponding α-methoxy-alkylhydroperoxides 17 and 21 . Key intermediate of the peroxide formation is the Criegee ozonization zwitterion which was trapped with acetaldehyde as an ozonide.     

Heat deterioration of phospholipids. VI. Clarification of mechanism for the new pseudo Maillard rearrangement reaction by using 2-aminoethyl dihydrogenphosphate

2,3-Dihydro-1H-imidazo[1,2-a]pyridine-4-ylium derivatives with UV absorption at 350 nm were formed by reaction of one molar of any sugar except 2-deoxysugars with two molar of phosphatidylethanolamines involving a new pseudo Maillard rearrangement reaction. To elucidate the reaction mechanism, 2-aminoethyl dihydrogenphosphate, which had a partially similar structural moiety to PE, was reacted with D-galactose. Though the UV absorption at 365 nm was not observed and the four pyridinium derivatives were also not formed in the reactant solution, the UV absorption at 286 nm and browning of the reactant solution were observed. From this reactant solution, two compounds with lambdamax at 283 nm and 297 nm were isolated and former was determined as 5-(hydroxymethyl)furfural (HMF) and later did as phosphoric acid mono{2-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]ethyl}ester (PMPEE), which is a new compound, respectively. Because reaction of PMPEE with PE leads to form the pyridinium derivatives, we concluded that a compound like PMPEE was one of intermediates in this new reaction.     

Darstellung von 1-Cyan-4-dimethylamino-3-(pyrid-4-yl)-buta-1,3-dien-1-carbonsäure-Derivaten und ihre Cyclisierung zu 3-substituierten 2-Amino-5-(pyrid-4-yl)-pyridinen sowie den entsprechenden 1-Oxiden

Synthesis of 1-Cyano-4-dimethylamino-3-(4-pyridinyl)-1,3-butadiene-1-carboxylic Acid Derivatives and Their Cyclisation to 3-Substituted 2-Amino-5-(4-pyridinyl)-pyridines Including the Corresponding 1-Oxides The vinylogous amidinium salt 1 is transformed to 1-cyano-4-dimethylamino-3-(4-pyridinyl)-1,3-butadiene-1-carboxylic acid derivatives 3a - f by reaction with the cyanoacetic acid compounds 2a - f in the presence of bases. Treatment of the 3a - f with ammonia and hydroxylamine yields the 2-amino-5-(4-pyridinyl)-pyridine-3-carboxylic acid derivatives 5a - f and the corresponding 1-oxides 6a - f , respectively. The products 5d , e are also prepared via the 6d , e by reduction with phosphorus trichloride.     

Action of Grignard reagents on thiophthalic anhydride, 3-benzal-2-thiophthalide, 3-p-chloro- and 3-p-methoxybenzalphthalides

Thiophthalic anhydride 1 reacts with the GRIGNARD reagents 2a – e (1:1 mol.) to give the corresponding 3-aryl(alkyl)-3-hydroxy-2-thiophthalides 3a – e . The interaction of 1 with 2c and f (1:2 mol.) yields the corresponding 1,2-diaroylbenzene derivatives 4 . On the other hand, 1 reacts with 2b (1:2 and 1:3 mol.) to give 5 and 6 , respectively. When 3-benzal-2-thiophthalide 7a and 3-p-chlorobenzalphthalide 7b are allowed to react with the GRIGNARD reagents 2c – f , the corresponding indenone derivatives 8 are obtained. On the other hand, the reaction of 7a and b with 2b (1:2 mol.) yields 6 and 9 , respectively. 7a and p-methoxybenzalphthalide 7c react with 2b (1:1 mol.) to give 5 and 10 ( a and b ). The constitution of the products has been investigated by means of IR and UV spectra.     

Funktionallsierung von lodprazolen mit D-Glucopyranose bzw. mit Aminoalkoholen

Functionalisation of Iodopyrazoles with D-Glucopyranose and with Aminoalcohols, Respectively . 3, 4, 5-Triiodo-pyrazole ( 1a ) and 3, 4-diiodo-5-methyl-1 H-pyrazole ( 1 b ) were silylated with hexamethyldisilazane without isolation of the N-trimethylsily derivatives and than glucosilated to give the β-N-nucleosides 2a and 2b , respectively, with 2, 3, 4, 6-tetra-O-acetyl-α-D-glucopy-ranosylbromide or -fluoride in the presence or absence of SnCl₄. The corresponding deacetylated derivatives 3 a – b can be easily obtained by treatment of 2 a – b with sodium methanolate in methanol. Furthermore, 1 a and 1 b as well as 3(5)-methoxycarbonyl-4-iodo-1-H-pyrazole ( 1 c ) were alkylated with methyl bromoacetate-acetate to form the corresponding pyrazole-1-yl-methylacetates 4 a – c . These compounds could be amidated by short heating with N-methylglucamine and 1-amino-propane-2, 3-diol (isoserinol), respectively, in methanol to form the corresponding amides 5 a – c and 6 a – c . The diamide 7 c was prepared bylongtime heating of 4 c with excess isoserinol in n-propanol.     

Produkte der Dimerisierung ungesättigter Fettsäuren VII: Kinetische Untersuchung der Mono- und Dimeren,die bei der Dimerisierung von Ölsäure entstehen

Products of the Dimerisation of Unsaturated Fatty Acids VII: Kinetic Studies about the Dimerisation of Oleic Acid The withdrawing of samples from a mixture of 95% oleic and 5% linoleic acid during dimerisation showed that oleic acid is first transferred into elaidic acid and its corresponding isomers with different positions of the double bond. Only these compounds are able to react to ?isostearic acids”? being found in the monomeric fraction. These findings were proven by the dimerisation of pure elaidic acid which gave identical products in identical quantities. Primary dimerisation products of this mixture of 95% oleic and 5% linoleic acid are formed by reaction of two molecules of linoleic acid or one molecule of linoleic acid with one molecule of oleic acid. The reaction products are partly of cyclic, partly of alicyclic structure. Isomerisation and hydrogenation occur only in the last period of the dimerisation process.     

Synthesis and characterization of substituted 2-diazo-1 -oxo-1,2-dihydzonaphthalenes and their products of photolysis and thermolysis

Several 2-diazo-1-oxo-1,2-dihydronaphthalene{ ( 1 , 2 ) have been synthesized by reaction of selected hydroxy compounds and 2-diazo-1-oxo-1,2-dihydzonaphthalene-5- and -4-sulfonylchloride, respectively. Photolysis as well as thermolysis of 1 and 2 leads to final products, the nature of which depends on the position of substitution. So, reactions of 5-substituted derivatives ( 1 ) yield the corresponding indene-3-carboxylic acids 3 and their esters 5 , respectively. In contrast, reactions of 4-substituted derivatives ( 2 ) lead to the formation of the 1-sulfo-indene-3-carboxylic acid derivatives 4 and 6 . Prepared compounds have been characterized by means of mass, ultraviolet, infrared, ¹H-n.m.r. ind ¹³C-n.m.r. {pectroscopy.     

Thermal degradation of single methyl oleate hydroperoxides obtained by Photosensitized oxidation

A peroxidation mixture containing methyl 9- and 10-hydroperoxy-trans-octadecenoates (MOHP) was obtained by singlet oxygen oxidation of methyl oleate. The two hydroperoxides were collected by solid phase extraction and purified separately by high-performance liquid chromatography. Identification and single-isomer purity evaluations were carried out by comparing the chromatographic and gas chromatography-mass spectrometry parameters of the corresponding reduced hydroxy derivatives. Each purified MOHP was thermally degraded and new reaction mechanisms were proposed from the identification of the degradation products. Thermal rearrangement of each hydroperoxide isomer involved an allylic 3-carbon intermediate before further degradation steps. The two MOHP isomers obtained from singlet oxygen oxidation produced all eight hydroperoxide isomers by thermal degradation in the condensed phase at high temperature (200°C). This result supports the assumption of singlet oxygen as a promoter of the first steps of oxidation of food lipids and also reconsiders the Khan mechanism.     

The STOBBE condensation. X. The cyclisation of (E)-3-methoxycarbonyl-4-(5′-methyl-2′-furyl)-but-3-enoic acid,and (E)−3-methoxycarbonyl-4-(2′-furyl)-pent-3-enoic acid,to Benzofuran Derivatives

The condensation of 5-methyl-furan-2-aldehyde and 2-furyl-methyl ketone with dimethyl succinate using either potassium t-butoxide or sodium hydride as condensing agents, gives predominantly (E)-3-methoxycarbonyl-4-(5′-methyl-2′-furyl)-but-3-enoic acid 1a and (E)-3-methoxy-carbonyl-4-(2′furyl)-pent-3-enoic acid 5 respectively. Their configurations are inferred by cyclisation with sodium acetate in acetic anhydride to the corresponding benzofuran derivatives 2,6 . Alcoholysis of (E)-3-carboxy-4-(5′-methyl-2′-furyl)-but-3-enoic anhydride 3 gives the half-ester 1c which is isomeric with the half-ester 1a . A competing side reaction also gives the self-condensation product of the succinic ester 4 .     

Thermal degradation of single methyl oleate hydroperoxides obtained by photosensitized oxidation

A peroxidation mixture containing methyl 9- and 10-hydroperoxy-trans-octadecenoates (MOHP) was obtained by singlet oxygen oxidation of methyl oleate. The two hydroperoxides were collected by solid phase extraction and purified separately by high-performance liquid chromatography. Identification and single-isomer purity evaluations were carried out by comparing the chromatographic and gas chromatography-mass spectrometry parameters of the corresponding reduced hydroxy derivatives. Each purified MOHP was thermally degraded and new reaction mechanisms were proposed from the identification of the degradation products. Thermal rearrangement of each hydroperoxide isomer involved an allylic 3-carbon intermediate before further degradation steps. The two MOHP isomers obtained from singlet oxygen oxidation produced all eight hydroperoxide isomers by thermal degradation in the condensed phase at high temperature (200°C). This result supports the assumption of singlet oxygen as a promoter of the first steps of oxidation of food lipids and also reconsiders the Khan mechanism.     

Action of acrylonitrile on 4-cyano- and 4-carbethoxy pyridazin-3(2H)-ones and their 3-mercapto derivatives. A novel Synthesis of Pyrano and Thiinopyridazines

Reaction of acrylonitrile with 4-cyano-5,6-diphenyl pyridazin-3(2H)-one and 3(2H)-thione derivative ( 1a, b ) at elevated temperature gave 7H-5-amino-6-cyano-3,4-diphenylpyrano and thiino [2,3-c] pyridazines ( 2a, b ), respectively. However, the reaction of 4-carbethoxy pyridazine derivatives ( 1c, d ) with the same reagent, under the same conditions afforded 6H, 7H-6-cyano-3,4-diphenyl-5-oxopyrano ( 3a ) and thiino [2,3-c] pyridazine ( 3b ), respectively. In addition, treatment of ( 1a, c ) and ( 1b, d ) with acrylonitrile ar reflux in alkaline medium give the respective 3-(2′-cyanoethyloxo) ( 7a, c ) and 3-2′-cyanoethylthio ( 7b, d ) pyridazine derivatives. Prolonged alkaline hydrolysis of either ( 1a, c ) or ( 7a, c ) yielded the same product ( 8a ). Also hydrolysis of ( 1b, d ) and ( 7b, d ) afforded one and the same product ( 8b ). The structures of the products were assigned on the basis of satisfactory analytical and spectroscopic data.     

Hydroaminomethylation of fatty acids with primary and secondary amines — A new route to interesting surfactant substrates

The rhodium catalysed hydroaminomethylation of the unsaturated fatty acid derivatives oleic acid ethyl ester (1) and oleyl alcohol (2) with the primary amines hexylamine (3) , benzylamine (4) , aspartic acid diethyl ester (5) and valinol (6) , and with the secondary amine morpholine (7) , respectively, proceeds with good to excellent yields. Using primary amines the structure of the reaction products depends on the stoichiometry of the reactants. Performing the reaction of (1) with (3) with an excess of the amine compound the corresponding secondary amine (9) (1:1‐adduct) was observed. Working with a 2‐fold excess of (1) the tertiary amine (16) (2:1‐adduct) was the main product.     

Synthese und Reaktionen von N-Phthalimido-keten-S,S-acetalen

Synthesis and Reactions of N-Phthalimido-ketene-S,S-acetals N-substituted phthalimido derivatives 1a – f react in the presence of bases (NaH, t-BuONa) with carbon disulfide to the N-phthalimido-ketene-S,S-acetals 3 , 4 , 5 and 6 , respectively. 2-Amino-ketene-S,S-acetals 7a – c are formed by reaction of 3a , b or 5a with hydrazine hydrate. 3c produces with phenylhydrazine the pyrazole 8 , and with piperidine and pyrrolidine the E/Z mixture of the corresponding ketene-S, N-acetals 9a , b . 1c is transformed into 10a – c (E/Z-mixture)by treatment with phenylisothiocyanate under basic condition followed by alkylation.     

Reactivity of the exocyclic double bond in 4-arylidene-2-phenyl-2-imidazolin-5-ones toward organomagnesium compounds. I

4-Arylidene-2-phenyl-1-substituted-2-imidazolin-5-ones 1a – d react with organomagnesium compounds, in ether at room temperature, to yield, as the main isolable products, the 4-disubstituted-methyl derivatives 2a – h . On the other hand, 1a – d react with phenylmagnesium bromide in a boiling ether-benzene mixture to give, among the reaction products, 2a – d and the 4-diarylmethylene derivatives 3a – d . Spectral data of 2 and 3 are discussed. Treatment of the GRIGNARD products 2a – c with formaldehyde and piperidine or morpholine effects aminomethylation at C-4 with the formation of the MANNICH bases 6a – f .     

Synthesis and some reactions of 1-(4.6-dimethoxybenzo-furanyl)- and 1-(4.6.7-trimethoxybenzofuranyl)butane-1.2.3-trione-2-arylhydrazones

Both 4.6-dimethoxy-( 1c ) and 4.6.7-trimethoxy-5-acetoacetylbenzofuran 1d are obtained from visnaginone ( 1a ) and khellinone methyl ethers 1b , respectively, by a CLAISEN condensation. The β-diketones 1c and 1d couple with aromatic diazonium compounds to form the hydrazones 2a – i . 1-(4.6-Dimethoxybenzofuranyl)- and 1-(4.6.7-trimethoxybenzofuranyl)butane-1.2.3-trione-2-arylhydrazones 2 a–i react with hydrazine hydrate in acetic acid to yield the corresponding pyrazole derivatives 3a–i or 4a–i . The monohydrazones 5a–b are isolated when 2e or 2i are treated with hydrazine hydrate in ethanol. The hydrazones are converted to the respective pyrazoles by the action of glacial acetic acid. Hydroxylamine hydrochloride reacts with 1.2.3-trione-2-arylhydrazones 2a, c, e, f and i to yield the corresponding isoxazole derivatives 6a–e or 7a–e . The 2-arylhydrazones 2a, c, d, e, h and i form the corresponding pyrazole derivatives 8a–f when treated with semicarbazide hydrochloride.     

Synthesen neuer Chinolon-Chemotherapeutika. V [5] Methodische Untersuchungen zur Synthese von Chinoloncarbonsäuren

Synthesis of Novel Quinolone-Chemotherapeutics. V. Methodical Investigations on the Synthesis of Quinolone Chemotherapeutics . The synthesis of 6, 7-dihalogen-N-ethyl-4-oxo-l, 4-dihydroquinoline-3-carboxylic acids ( 3a , b ) from 3, 4-dihalogen-anilines is a three-step processes: (a) N-ethylation, (b) reaction with ortho formic ester and Meldrum's acid, (c) intramolecular cyclization. An increase of the total yields in comparison with known methods is mainly connected with the third step. Here the Meldrum's method allows reactions in solution at temperatures ≥ 100°C. With application of special Lewis acids the 6, 7-dihalogen-substituted products are formed in relatively high yields (6, 7-difluoro-l-ethyl-4-oxo-1, -4-dihydro-quinoline-3-carboxylic acia ( 3a ): 71%; 7-chloro-6-fluoro-1 -ethyl-4-oxo-1, 4-dihydro quinoline-3-carboxylic acid ( 3b ): 60%) without impurities of the corresponding 5, 6-dihalogen substituted isomers. Anhydrides ( 5 ) of 4-oxo-1, 4-dihydro-quinolone-3-carboxylic acids with dibromo and difluoro-boric acid were synthesized and shown to facilitate the aromatic nucleophilic substitution. The kinetics of two reactions ( 5a → 6 and 3b → 7 ) were determined and relative reaction rates established.     

A possible role for singlet oxygen in the initiation of fatty acid autoxidation

A mechanism for the initiation of autoxidation in fatty acids is proposed which involves singlet state oxygen, formed through a photosensitization reaction, as the reactive intermediate. Both singlet oxygen generated in a radio-frequency gasdischarge, and photosensitization by natural pigments, were shown to catalyze the oxidation of methyl linoleate. The involvement of singlet oxygen was shown by the identification of nonconjugated hydroperoxides as products common to both photooxidation and singlet O₂ oxidation. Nonconjugated hydroperoxides could not be detected among the free radical autoxidation products. Further proof for the above mechanism was gained by showing that compounds known to react strongly with singlet oxygen, inhibited the photooxidation. With the exception of chlorophyll, all sensitizers could be completely inhibited. Although singlet oxygen formation can account for approximately 80% of the observed chlorophyll photooxidation, at least one other mechanism must be involved. It is postulated that proton abstraction by the photoactivated carbonyl group of chorophyll could account for the remaining 20% of the observed photooxidation. The conclusion is drawn that oxygen, excited to its singlet state by a photosensitization process, plays the important role of forming the original hydroperoxides whose presence is necessary before the normal free radical autoxidation process can begin.     

Strukturelle Abwandlungen an N-Acetylneuraminsäure. 22 [1]. Zur Umsetzung von Methyl-5-acetamido-7,8-anhydro-4-O-t-butyldimethylsilyl-3,5-didesoxy-D-glycero- und L-glycero-β-D-galakto-nonulopyranosidonsäure-methylester mit Bis-imidazolylthiocarbonat

Structural Variations on N-Acetylneuraminic Acid. 22 On the Reaction of Methyl[5-Acetamido-7,8-anhydro-4-O-t-butyldimethylsilyl-3, 5-dideoxy-D-glycero-and-L-glycero-β-galacto-2-nonulopyranosid]onate with Diimidazolylthiocarbonate The title compounds 1 and 3 are transformed with diimidazolylthiocarbonate into the cyclic 8(S),9(O)-dithiocarbonatosialic acid derivatives 2 and 4 as well as into a mixture of the cyclic 8(S),9(O)-monothiocarbonato derivatives 5a and 5b , which turned with acetanhydride pyridine to the corresponding 4-O-t-butyldimethylsilyl-7-O-acetyl- and 4,7-di-O-acetyl derivatives 5c and 5d .