Action of hydrogen peroxide on some 2-aminooxazoles and imidazolin-2-ones. Isolation of hydroperoxyimidazolidin-2-ones

The reaction of some 2-aminooxazoles and imidazolidin-2-ones with hydrogen peroxide afforded stable trans-β-hydroxyhydroperoxy- or dihydroperoxyimidazolidin-2-ones according to the reaction conditions. In the case of 3a-hydroxy-7a-hydroperoxyoctahydro-2H-benzimidazolidin-2-one, the trans isomer is forbidden and cis adduct was isolated. A radical pathway to these hydroperoxides is proposed. From 2-amino-4-methyloxazole and hydrogen peroxide 2-amino-2-hydroxy-4-methyloxazolidin-4-yl peroxyacetate was also isolated.     

Access to the 2,3-dihydropyridazin-3-one and as-triazino[3,4-a]phthalazine ring systems from 4-aryl-2-oxo-butanoic acids

A novel series of 2,3-dihydropyridazin-3-ones 15 were synthesized via condensation between hydrazines and 4-(p-chlorophenyl)-2-hydroxy-2-(2-oxo-2-substituted ethyl)butanoic acids 8 which in turn were prepared by the reaction of substituted benzylpyruvic acids 6 with methyl alkyl(aryl) ketones 7. Dehydration of 8b-d by a mixture of glacial acetic acid and hydrochloric acid afforded 4-(p-chorophenyl)-2-(substituted phenacyl)-2-butenoic acids 10. Condensation reaction of 10 with hydrazines gave type 15 compounds in good yields. Also, a new series of as-triazino[3,4-a]phthalazines 20 was obtained from the reaction of substituted benzylpyruvic acids 6 with hydralazine to give the hydralazones 19 which underwent dehydrative cyclization reaction with PPA to afford 20. Structure assignments are based on ¹H, ¹³C nmr and ir spectra.     

Direct heterocyclization of tetrahydroisoquinolin-1-ylideneacetic acids by the action of 5-arylfuran-2,3-diones

Aroylketenes generated in situ by thermolysis of 6-aryl-2,2-dimethyl-4H-1,3-dioxin-4-ones reacted with 3,3-dialkyl-1-methyl-3,4-dihydroisoquinolines to give (1Z,3Z)-4-aryl-4-hydroxy-1-[3,3-dialkyl-3,4-dihydroisoquinolin-1(2H)-ylidene]but-3-en-4-ones. The crystalline and molecular structure of (1Z,3Z)-4-hydroxy-1-[6,7-dimethoxy-3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-ylidene]-4-phenylbut-3-en-2-one was studied by X-ray diffraction.     

Synthesis of 6-substituted 3-cyano-5-nitropyridine-2(1H)-thiones

The reactions of 1-substituted 2-nitro-3-phenylaminoprop-2-en-1-ones with cyanothioacetamide afforded the corresponding 6-substituted 3-cyano-5-nitropyridine-2(1H)-thiones, which were used for the synthesis of 6-substituted 3-cyano-2-methylthio-5-nitropyridines and 7-substituted 4-hydroxy-8-nitropyrido[2",3":4,5]thieno[2,3-b]pyridin-2(1H)-ones.     

Total synthesis of two γ-butyrolactone containing compounds (Z,11S)-3,4-trans-11-hydroxy-3-methyldodec-cis-6-en-4-olide and (Z)-3,4-trans-11-oxo-3-methyldodec-cis-6-en-4-olide

The first total synthesis of (Z,11S)-3,4-trans-11-hydroxy-3-methyldodec-cis-6-en-4-olide and (Z)-3,4-trans-11-oxo-3-methyldodec-cis-6-en-4-olide was accomplished using Jacobsen hydrolytic kinetic resolution, Ohira–Bestmann reaction, regioselective alkyne addition to terminal carbon atom of epoxide, intramolecular TEMPO/BAIB mediated oxidative lactonization and partial hydrogenation as the key steps.     

Total synthesis of (6Z,9S)-3,4-trans-9-hydroxy-3-methyldodec-cis-6-en-4-olide and (6Z)-3,4-trans-9-oxo-3-methyldodec-cis-6-en-4-olide γ-butyrolactones

The first total synthesis of (6Z,9S)-3,4-trans-9-hydroxy-3-methyldodec-cis-6-en-4-olide and (6Z)-3,4-trans-9-oxo-3-methyldodec-cis-6-en-4-olide was achieved in a convergent pathway. The salient features of our synthesis include Ohira–Bestmann reaction, regioselective alkyne addition to terminal epoxide, TEMPO/BAIB mediated oxidative lactonization, and partial hydrogenation.     

Saturated heterocycles, 248. Synthesis of 2,4-dioxo and 4-oxo-2-thioxo derivatives of octahydrocyclopenta[d]pyrimidines

Unsubstituted and 1-benzyl-substituted cis-cyclopenta[d]pyrirnidine-2,4-diones and cis-2-thioxo-cyclopenta[d]pyrimidin-4-ones 9a,b and 10a,b were prepared from the corresponding cis-2-amino-1-cyclopentanecarboxylates 3 and 5 with potassium cyanate and thiocyanate. It was found that the cis derivatives 7a-h readily underwent ring closure, resulting in 3-substituted cis-2,4-cyclopenta[d]pyrimidinediones and cis-2-thioxocyclopenta[d]pyrimidin-4-ones 11a-d and 12a-d , whereas the trans counterparts 8a-d failed to cyclize, but gave hydrolysed amino acid derivatives 13a,b and 14 . This difference in the reactivities of the cis and trans isomers is a further example of the difficulty of preparing cyclopentane trans-fused six-membered 1,3-heterocycles by ring closure.     

Stereochemistry of alkyl 3-substituted 4-halotetrahydro-2-oxo-3-furancarboxylates: 2—1H and 13C NMR spectra

The ¹H NMR parameters of methyl 3-substituted cis-4-halotetrahydro-2-oxo-3-furancarboxylates are reported, with assignments of the ring protons based on solvent-induced changes in the vicinal trans coupling constants, ³J(H-4, H-5). Preferred conformations, ce with a pseudo-equatorial halogen for the cis isomers and ta with a pseudo-axial halogen for the trans isomers, have been suggested on comparison of the magnitudes of J(trans) and J(gem) in both series. The ³J(¹³CH₃, H-4) values measured for methyl cis-4-bromotetrahydro-3-methyl-3-furancarboxylate, methyl trans-4-bromotetrahydro-3-methyl-3-furancarboxylate and trans-3,4-dibromodihydro-3-methyl-2(3H)-furanone have confirmed the stereochemical assignments.     

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.     

1-Oxa-3-azapentalen-2-ones as Precursors of cis-2-Amino Alcohols: Synthesis from Propargyl Alcohols, CO2, and Amines Using an Intramolecular Amidoalkylation Reaction of Oxazolidin-2-ones

The reaction of 5-methyl-5-(4-methyl-3-pentenyl)-4-methylene-1,3-dioxolan-2-one with primary amines gives the corresponding 4-hydroxy-4-methyloxazolidin-2-ones. These undergo an intramolecular amidoalkylation reaction to form 1-oxa-3-azapentalen-2-ones which are potential precursors of cyclopentanyl cis-2-amino alcohols.     

Synthesis of 1,5-disubstituted (E)-pent-2-en-4-yn-1-ones

The condensation of 3-arylpropynals with aryl methyl ketones in the presence of sodium hydroxide in 50% aqueous ethanol at 0°C (Claisen-Schmidt reaction) afforded up to 89% of the corresponding (E)-1,5-diarylpent-2-en-4-yn-1-ones. The E configuration of the double C=C bond and cis conformation of the enone fragment in the products in crystal and CDCl₃ solution were determined by X-ray analysis and ¹H NMR spectroscopy.     

The Terpenoids of Maytenus boaria MOL. (Celastraceae)

The known triterpenoids β-amyrin (= olean-12-en-3β-ol; 22 ), lupeol (= lup-20(29)-en-3β-ol; 17 ), betulin (= lup-20(29)-ene-3β,28-diol; 18 ), lup-20(29)-ene-3β,30-diol ( 20 ), oleanolic acid (= 3β-hydroxyolean-12-en-28-oic acid; 21 ), and betulonic acid (= 3-oxolup-20(29)-en-28-oic acid; 19 ), together with epicatechol (= cis-2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3,5,7-triol; 23 ), 5′-O-methylgallocatechol (= trans-2-(3,4-dihydroxy-5-methoxyphenyl)-3,4-dihydro-2H-1-benzopyran-3,5,7-triol; 24 ), and 4-hydroxybenzaldehyde were isolated from the aerial parts of Maytenus boaria (MOL. ). Additonally, the eight 4,C⁴-dihydro-β-agarofuran sesquiterpenoids 1–8 , one of them a diol with a (4R)-configuration, and compound 9 were present in the extract. The structures of these compounds were established by spectroscopic and chemical means.     

Reduction of 6/7-substituted 3-phenyltrop-3-en-2-ones: stereoselectivity and conformational analysis of the products

Reduction of 6/7-carboethoxy-3-phenyltrop-3-en-2-ones with H₂/Pd/C and NaBH₄ was studied in order to find a stereoselective route to the corresponding 3-phenyltropan-2-ones and 2α/2β-hydroxy-3-phenyltropanes. The 6/7-exo-carboethoxy-3-phenyltrop-3-en-2-ones were selectively reduced by Pd/C to 3β-phenyltropan-2-ones and 2α-hydroxy-3β-phenyltropanes. The corresponding 2β-hydroxy-3β-phenyl analogues were synthesized using NaBH₄, with a yield of 40%. Reduction of 6-endo-carboethoxy-3-phenyltrop-3-en-2-one yielded several products. The corresponding 7-endo-substituted analogue was selectively reduced with both Pd/C and NaBH₄ to 7-endo-carboethoxy-3β-phenyltropin-2-one. Analysis of stereochemically important ¹H NMR spectroscopy parameters was performed for all the products and used for conformational analysis in solution. X-ray analysis was performed for selected compounds.     

Facile addition of methyl lithium to a 4-vinylpyridine system

The rapid addition of methyl lithium to the 4-vinylpyridine system present in 4-{2,6-dihydroxy-4-(3-methyl-2-octyl)phenyl}-2-methyl-4-(4-pyridyl)but-3-en-2-ol ( 2 ) is reported. The α and β-4-{2,6-dihydroxy-4-(3-methyl-2-octyl)phenyl}-2,3-dimethyl-4-(4-pyridyl)butan-2-ols 4 and 5 formed, are cyclised by heating with 5N hydrochloric acid to trans and cis-3,4-dihydro-5-hydroxy-7-(3-methyl-2-octyl)-4-(4-pyridyl)-2,2,3-trimethyl-2H-1-benzopyran 6 and 7 respectively.     

Reactions of 3-amino-1-phenyl- and 3-amino-1-(thien-2-yl)-4,4,4-trifluorobut-2-en-1-ones with 1,2-diaminopropane and 1,2-diamino-3,3,3-trifluoropropane

The reactions of 3-amino-1-phenyl-and 3-amino-1-(thien-2-yl)-4,4,4-trifluorobut-2-en-1-ones with 1,2-diaminopropane under kinetically controlled conditions afford mixtures ofcis andtrans isomers of 2-aroylmethyl-4-methyl-2-trifluoromethylimidazolidines. Analogous reactions with 1,2-diamino-3,3,3-trifluoropropane yieldcis-2-aroylmethyl-2,4-bis(trifluoro-methyl)imidazolidines. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2135–2139, November, 1999.     

Reactions of 3-hydroxy-1,2-dihydroquinazolin-4-ones with aldehydes

The reactions of 3-hydroxy-2-(2-hydroxyalkyl)- [or (2-hydroxyaryl)]-1,2-dihydro-quinazolin-4-ones with formaldehyde or acetaldehyde afford 1,3-oxazino[3,4-a]quinazolin-4-one derivatives. The reactions with other aldehydes RCHO and 3-hydroxy-2-R′-1,2-dihydroquinazolin-4-ones can give 3-hydroxy-2-R-1,2-dihydroquinazolin-4-ones, 2-substituted quinazolin-4-ones, or dianthranilide. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2523–2526, December, 1998.     

Synthesis of syn- and anti-tricyclo [4.1.0.02,4] heptan-5-ones and related compounds

A convenient entry to both title compounds 1 and 2, as well as to cis- and trans-4-iodomethyl-bicyclo [3.1.0]-hexan-2-ones 3and 4 and to 4-methyl-bicyclo [3.1.0]-hex-3-en-2-one 5 involving base-promoted reactions of cis- and -trans-3,4-diiodomethylcyclopentanones 6 and 7 is reported, and the behaviour of 6 and 7 towards different bases. bfv40bp4761b     

Tetracarbonyl Systems: VII. Reactions of 1,3,4,6-Tetracarbonyl Compounds with o-Aminothiophenol in the Synthesis of Regioisomeric 3(2)-Aroylmethylene-1,4-benzothiazin-2(3)ones

In reaction of 1,6-diaryl-3,4-dihydroxy-2,4-hexadiene-1,6-diones with o-aminothiophenol (3Z)-3-aroylmethylene-3,4-dihydro-2H-1,4-benzothiazin-2-ones were obtained in a preparative yield. In solution of the latter compounds an enamine-imine tautomerism was observed. In reaction of ethyl esters or amides of 2-substituted 6-aryl-3,4-dihydroxy-6-oxo-2,4-hexadienoic acids with the o-aminothiophenol regioisomeric 2-aroylmethylene-2H-1,4-benzothiazin-3(4H)-ones were formed.     

Pteridines. Part LXXXVII. Synthesis and Properties of 8-Substituted 2-Thiolumazines

Various 8-substituted 2,8-dihydro-2-thioxopteridin-4(3H)-ones ( 14 – 21 ) and 2-(methylthio)pteridin-4(8H)-ones ( 27 – 32 ) have been synthesized by condensation of the appropriate 5-amino-6-(substituted amino)-1,2-dihydro-2-thioxopyrimidin-4(3H)-ones ( 22 – 34 ) and 5-amino-6-(substituted amino)-2-(methylthio)pyrimidin-4(3H)-ones ( 25 , 26 ), respectively, with glyoxal, biacetyl, and benzil. The presence of a quinonoid cross-conjugated π-electron system makes this type of compounds susceptible to nucleophilic additions in position 7, which leads to intramolecular ( 43 , 45 ) and intermolecular ( 44 ) covalent adducts. The newly synthesized compounds have been characterized by elemental analyses, pK_a determinations, ¹H-NMR and UV spectra. UV-Spectral changes in dependence of the pH are associated with the most appropriate molecular species including the monocations, neutral forms, covalent adducts, mono- and dianions.     

Reactions of aromatic ketones with 3-mercapto-1,2-propanediol. Synthesis of cis- and trans-2-alkyl-2-aryl-(1,3-oxathiolane-5-methanols and 1,3-dioxolane-4-methanethiols)

Aromatic ketones react with 3-mercapto-1,2-propanediol ( 1 ) in refluxing benzene under the catalytic influence of a sulfonic acid and with azeotropic removal of water to yield a mixture comprised predominantly of cis- and trans-2-alkyl-2-aryl-1,3-oxathiolane-5-methanols 7, accompanied by lesser amounts of cis- and trans-2-alkyl-2-aryl-1,3-dioxolane-4-methanethiols 8 (up to 30%). It was discovered that 8 is the kinetic product and is isomerized by 4-toluenesulfonic acid in hot benzene to the thermodynamically more stable 7 . Under these conditions, ortho- and α-substituted aromatic ketones tend to produce more of 8 , which can be attributed to steric hindrance encountered by the thiol as it attacks the ketone. Ketalizations of 1-aryl-2-(1H-imidazol-1-yl)-1- as well as 1-aryl-2-(1,H-1,2,4-triazol-1-yl)-1-ethanones by 1 fail under these conditions, even after 24 hours of reflux in toluene. However, 1-(4-chlorophenyl)-3-(1H-imidazol-1-yl)-1-propanone and 1-(4-bromophenyl)-4-(1H-imidazol-1-yl)-1-butanone are ketalized by 1 as expected. Interestingly, the reaction of 2-bromo-4′-chloroace-tophenone with 1 produces 1-(4-chlorophenyl)-2,8-dioxa-6-thiabicyclo[3.2.1]octane. Characterization of all isomers and separation of some diastereomers is described. Nuclear Overhauser enhancement experiments are utilized to establish the stereochemistry of 1,3-oxathiolanes.