Synthesis of novel 2-phenyl-5-substituted dihydropyrimidines using 2-phenyl-1,3-diaza-1,3-butadienes and electron-deficient olefins

A novel synthetic method for 2,5-disubstituted dihydropyrimidines was developed. The cyclization of 1,3-diaza-4-dimethylamino-1,3-butadienes having a N-protecting group (N-Boc, N-Cbz, N-n-C₄H₉, N-Bn or N-Ph) with electron-deficient olefins, such as α,β-unsaturated carbonyl compounds, phenyl vinyl sulfone, and acrylonitrile was studied in detail. The cyclization smoothly proceeded to afford 4-dimethylamino-1,4,5,6-tetrahydropyrimidines or 1,6-dihydropyrimidines in good yields. The isolated 4-dimethylamino-1,4,5,6-tetrahydropyrimidines were converted to 2,5-disubstituted-1,6-dihydropyrimidines through the β-elimination of the dimethylamino group. 2,5-Disubstituted-1,4(6)-dihydropyrimidines were obtained after removal of the N-Boc or N-Cbz group. Independent tautomers of the resulting dihydropyrimidines were observed.     

Preparation of 1,3-dienyl organotrifluoroborates and their Diels-Alder/cross-coupling reactions

2-BF₃-substituted 1,3-butadienes with potassium and tetrabutyl ammonium counterions have been prepared in gram quantities from chloroprene via a simple synthetic procedure. The potassium salt of this new main group element substituted diene has been characterized by ¹H, ¹³C, ¹¹B, and ¹⁹F NMR and the tetra n-butyl ammonium salt was also characterized by X-ray crystallography. Diels-Alder reactions of these dienes with dienophiles such as ethyl acrylate, methyl vinyl ketone, and N-phenylmaleimide are reported as well as subsequent Pd-catalyzed cross-coupling reactions of those Diels-Alder adducts. 4-Phenyl-2-BF₃-substituted 1,3-diene was prepared by magnesium-halogen exchange from the corresponding 2-bromo and iodo dienes. The 4-phenyl-2-bromo-1,3-butadiene was also characterized by X-ray crystallography. 4-Phenyl-2-BF₃-1,3-butadiene was used in Diels-Alder/cross-coupling reactions and the product of a Diels-Alder reaction with N-phenylmaleimide followed by cross-coupling with 4-bromo-benzonitrile was also characterized by X-ray crystallography.     

Aza-Morita–Baylis–Hillman reaction with ion-supported Ph3P

Various N-tosyl arylimines reacted with methyl vinyl ketone and ethyl vinyl ketone in the presence of ion-supported Ph₃P A and B to give adducts, N-(2′-methylene-3′-oxo-1′-arylbutyl)-4-methylbenzenesulfonamides and N-(2′-methylene-3′-oxo-1′-arylpentyl)-4-methylbenzenesulfonamides, respectively, in good yields with high purity by simple diethyl ether extraction of the reaction mixture. Moreover, ion-supported Ph₃P A and B could be repeatedly used for the same reaction to provide the corresponding adducts while maintaining good yields with high purity.     

Lewis acid mediated SN2-type nucleophilic ring opening followed by [4+2] cycloaddition of N-tosylazetidines with aldehydes and ketones: synthesis of chiral 1,3-oxazinanes and 1,3-amino alcohols

A highly efficient strategy for Cu(OTf)₂ mediated S_N2-type nucleophilic ring opening followed by [4+2] cycloaddition reactions of enantiopure 2-phenyl-N-tosylazetidines with various aldehydes and ketones afforded a variety of substituted 1,3-oxazinanes and 1,3-amino alcohols in excellent yields, excellent de and good to excellent ee. The proposed S_N2-type mechanism of the cycloaddition reaction is supported by experimental evidence.     

N-(1,3-Thiazol-5(4H)-yliden)amine aus 1,3-dipolaren Cycloadditionen von Aziden mit 1,3-Thiazol-5(4H)-thionen

N-(1,3-Thiazol-5(4H)-ylidene)amines via 1,3-Dipolar Cycloaddition of Azides and 1,3-Thiazol-5(4H)-thiones Organic azides 5 and 4,4-dimethyl-2-phenyl-1,3-thiazol-5(4H)-thione ( 2 ) in toluene at 90° react to give the corresponding N-(1,3-thiazol-5(4H)-ylidene)amines (= 1,3-thiazol-5(4H)-imines) 6 in good yield (Table). A reaction mechanism for the formation of these scarcely investigated thiazole derivatives is formulated in Scheme 3: 1,3-Dipolar azide cycloaddition onto the C?S group of 2 leads to the 1:1 adduct C . Successive elimination of N₂ and S yields 6 , probably via an intermediate thiaziridine E .     

Reaction of polychloroacetaldehyde arylsulfonylimines with 2-amino-6<Emphasis Type="Italic">H</Emphasis>-1,3-thiazine-6-thiones and 2-amino-4-phenyl-6<Emphasis Type="Italic">H</Emphasis>-1,3-thiazin-6-one

2-Amino-4-R-6H-1,3-thiazine-6-thiones and 2-amino-4-phenyl-6H-1,3-thiazin-6-one react with highly electrophilic N-arylsulfonylimines of chloral and phenyldichloroacetic aldehyde at the exocyclic amino group affording in good yields products of nucleophilic addition to the azomethine group of imines: N-[2-polychloro-1-(6-thioxo-4-R-6H-1,3-thiazin-2-ylamino)ethyl]- or -[2-polychloro-1-(6-oxo-4-phenyl-6H-1,3-thiazin-2-ylamino)ethyl]arenesulfonamides.     

Cleavage of C-Si bond by intramolecular nucleophilic attack: lithiation-promoted formation of siloles from 1-bromo-4-trisubstituted silyl-1,3-butadiene derivatives

Lithiation of 1-bromo-4-trisubstituted silyl-1,3-butadiene derivatives with t-BuLi afforded substituted siloles in high yields. Cleavage of one of the three C-Si bonds took place via intramolecular nucleophilic substitution. Selective cleavage was observed when the silyl group possessed different substituents. Results showed that vinyl and phenyl substituents on Si were substituted much more easily than methyl groups, whilst a methyl group was exclusively deleted from an i-Pr-SiMe₂ moiety.     

Vinyl polymerization versus [1,3] O to C rearrangement in the ruthenium-catalyzed reactions of vinyl ethers with hydrosilanes

Two reactions, vinyl polymerization and [1,3] O to C rearrangement of vinyl ethers, are investigated in the ruthenium-catalyzed reaction with hydrosilanes. The reaction pathways are dependent on the substituents of the vinyl ether, in particular, those of the alkoxy group. Primary-, secondary-, and tertiary-alkyl vinyl ethers, ROCHCH₂, are polymerized with ease to give the corresponding polymer in good yields. When R is electron-donating benzyl groups, the reaction does not give the polyvinyl ether but results in [1,3] O to C rearrangement to give the corresponding aldehyde, RCH₂CHO in moderate to good yields. The rearrangement selectively proceeds when vinyl ethers having α-substituents are used as the starting materials to give the corresponding ketones in high yields. With catalytic amounts of hydrosilanes, the rearrangement gives ketones or aldehydes selectively. In sharp contrast, use of excess amounts of hydrosilanes leads to the rearrangement followed by reduction of the formed carbonyl group to give the corresponding silyl ethers in good yields. Nature of catalytically active species is discussed.     

Orthogonal synthesis of pyrroles and 1,2,3-triazoles from vinyl azides and 1,3-dicarbonyl compounds

Tri- and tetrasubstituted N-H pyrroles were prepared by the simple treatment of vinyl azides with 1,3-dicarbonyl compounds in toluene at 100 °C via 2H-azirine intermediates generated in situ. When the reactions of vinyl azides and 1,3-dicarbonyl compounds were performed in DMF in the presence of a catalytic amount of K₂CO₃, 1-vinyl-1,2,3-triazoles were obtained via 1,3-dipolar cycloaddition. These methodologies exploited orthogonal modes of chemical reactivity of vinyl azides, which could be achieved by slight modification of the reaction conditions.     

Kinetics of reactions between arylnitroso oxides and methyl vinyl ketone

The kinetics of the reactions of phenylnitroso oxide, (4-methylphenyl)nitroso oxide, (4-methoxyphenyl) nitroso oxide, 4-(N, N -dimethylamino)phenylnitroso oxide, (4-chlorophenyl)nitroso oxide, (4-bromophenyl) nitroso oxide, and (4-nitropenyl)nitroso oxide with methyl vinyl ketone in acetonitrile at 295 K was studied. With the use of 4-CH₃O-C₆H₄-NOO as an example, it was found that only the trans isomers of nitroso oxides entered into the reaction. The rate constants of the reactions of the trans isomers of nitroso oxides with methyl vinyl ketone were measured. A linear correlation between the logarithms of reaction rate constants and the electronic properties of substituents in the aromatic rings of nitroso oxides on the Hammett scale was established: ρ = 1.11 ± 0.08; r = 0.990.     

Synthesis of new imidazo[2,1-<Emphasis Type="Italic">b</Emphasis>][1,3]thiazole derivatives from 2-amino-4-(2,2-dichlorovinyl)-1,3-thiazole and <Emphasis Type="Italic">N</Emphasis>-(2,2-dichloro-2-phenylethylidene)arenesulfonamides

2-Amino-4-(2,2-dichlorovinyl)-1,3-thiazole reacted with highly electrophilic N-(2,2-dichloro-2-phenylethylidene)- and N-(2,2,2-trichloroethylidene)arenesulfonamides through the exocyclic amino group to give products of nucleophilic addition to the azomethine bond, N-[2,2-di(or 2,2,2-tri)chloro-1-(1,3-thiazol-2-ylamino)ethyl]arenesulfonamides in good yields. Intramolecular heterocyclization of the latter afforded N-[3-(2,2-dichloroethyl)-6-phenylimidazo[2,1-b][1,3]thiazol-5-yl]arenesulfonamides.     

Reaction of electron deficient NN bonds with acyloxyketenes and mesoionic 1,3-dioxolium-4-olates: fast equilibrium between acyloxyketenes and mesoionic 1,3-dioxolium-4-olates

Reaction of azodicarboxylates with acyloxyketenes arising from dehydrochlorination of acyloxyphenylacetyl chlorides was carried out to give triacylamidine derivatives in good yields. The same triacylamidine derivatives were also obtained in good yields from the reaction with mesoionic 1,3-dioxolium-4-olates generated by Rh₂(OAc)₄-catalyzed decomposition of phenyldiazoacetic anhydride derivatives. Formation of the same compounds from different starting materials is explained by 1,3-dipolar addition between electron deficient NN bonds and mesoionic 1,3-dioxolium-4-olates, indicating fast equilibrium between acyloxyketenes and mesoionic 1,3-dioxolium-4-olates.     

Synthesis of 5-(perfluoroalkylmethyl)-1,3-dioxolan-4-ones

Acid catalysed condensation of F-alkyl α-hydroxy acids with simple aldehydes or ketones gave F-alkyl 1,3-dioxolan-4-ones. When BF₃,OEt₂ was used as the catalyst, the condensation products were obtained in moderate to good yields and the “cis” isomers are largely favoured, while with HOTs/H₂SO₄ as catalyst, poor yields and lower stereoselectivities were observed.     

Aza-Baylis-Hillman reaction of salicyl N-tosylimines with methyl vinyl ketone, ethyl vinyl ketone or phenyl vinyl ketone

Reactions of salicyl N-tosylimines with methyl vinyl ketone, ethyl vinyl ketone or phenyl vinyl ketone proceeded smoothly under mild conditions to give the corresponding chromanes or aza-Baylis-Hillman adducts in moderate to excellent yields in the presence of phosphine or nitrogen Lewis base.     

A novel synthesis of 4,5-diaryl-6-arylamino-2,3-benzo-1,3a,6a-triazapentalenes

Treatment of N-alkyl- and N-aryl-imines of 2,3-diaryl- and 2-alkyl-3-aryl-3-(benzotriazol-1-yl)propenals with trifluoroacetic anhydride in THF at room temperature gave 5-alkyl-4-aryl-6-[N-alkyl (and aryl)-N-trifluoroacetyl]amino-2,3-benzo-1,3a,6a-triazapentalenes in moderate to good yields. On heating triazapentalenes having R²=aryl in MeOH at reflux, detrifluoroacetylation of triazapentalene occurred to give title compounds in good yields. However, the same treatment of triazapentalenes having R²=alkyl did not give the corresponding detrifluoroacetylation product. The title compounds and 5-alkyl-4-aryl-6-(N-alkyl-N-trifluoroacetyl)amino-2,3-benzo-1,3a,6a-triazapentalenes were found to be good precursors for the synthesis of 1-(o-aminophenyl)-3-arylamino-4-alkyl (and aryl)-5-arylpyrazoles and 1-(o-aminophenyl)-3-(N-alkyl-N-trifluoroacetyl)amino-4-alkyl (and aryl)-5-arylpyrazoles, respectively.     

Sulfoxide-controlled SN2′ displacements between cuprates and vinyl and alkynyl epoxy sulfoxides

The S_N2′ displacement of readily available vinyl epoxy sulfoxides with organocopper reagents takes place in good yields with high anti selectivity and a good degree of E/Z stereocontrol to produce enantiopure α-hydroxy vinyl sulfoxides. A second allylic displacement on the related mesyloxy vinyl sulfoxides allows for the asymmetric construction of two adjacent chiral centers. In addition, cuprate mediated S_N2′ addition to alkynyl epoxy sulfoxides affords α-hydroxy allenyl sulfoxides in good yields.     

Vibrational and electronic spectral studies of substituted 1,3-dihydro-1,3-diphenyl-2-thioxo-2H,5H-pyrimidine-4,6-diones

The vibrational spectra of 1,3-diphenyl-; 1,3-di (4′-chlorophenyl)-; 1,3-di(3′-methoxyphenyl)-1,3-dihydro-2-thioxo-2H,5H-pyrimidine-4,6-diones in solid state (KBr pellet) and in solution (CHCl₃ and CCl₄) have been studied and assignments made. Tautomeric and hydrogen bonding behaviour are discussed. Electronic spectra in various solvents at different pH values are recorded. The effect of substituents, change of solvent on the π—π* and n—π* transitions of all the compounds is explained. The bathochromic and hypsochromic shifts observed when the neutral form changes to the cationic or anionic form depending on the pH of solution, are also discussed.     

Mild bromination of unreactive aromatic compounds

N,N,N′,N′-Tetrabromobenzene-1,3-disulfonamide and poly(N,N′-dibromo-N-ethylene-benzene-1,3-disulfonamide) in concentrated H₂SO₄ can be used as efficient reagents for the mild bromination of unreactive arenes at room temperature, under solvent-free conditions, in good yields.     

The unexpected cyclization routes of N,N′-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines in polyphosphoric acid medium

The unexpected results of the cyclization reactions of N,N′-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines [1,3-C₆H₄-(NHCRCHC(O)CF₃)₂], where R = H, Me, and Ph, in a strongly acidic medium (PPA), allowing the synthesis of new trifluoromethylated heterocycles containing the 1,7-phenanthroline nucleus in 32-40% yields and 7-aminoquinolines (38-40% yields), is reported. The bis-enaminoketone intermediates were easily isolated from the reactions of 4-alkoxy-4-alkyl(aryl)-1,1,1-trifluoroalk-3-en-2-ones with 1,3-phenylenediamine in ethanol under mild conditions (68-86% yields).     

Perfluoro alkyl 1,3-diketonates of cyclic and acyclic secondary amines

Cyclic and acyclic secondary amines were quaternized with perfluoroalkyl 1,3-diketones to form secondary ammonium perfluoroalkyl 1,3-diketonates in good yields. Saturated cyclic secondary amines, including morpholine, N-acetylmorpholine, 3-methyl-N-acetylpiperidine, 2,2,6,6-tetramethyl-4-aminopiperidine, 4,4-dimethylimidazoline, 1,3-bispiperidine propane, and acyclic secondary amines, di(n-propyl) amine, di(isopropyl) amine, di(n-butyl) amine, and di(isobutyl) amine were reacted with various fluorine-containing 1,3-diketones (1-5) to yield the corresponding 1,3-diketonates (6-29). The compounds were characterized by ¹H, ¹⁹F, and ¹³C NMR, electrospray MS, and elemental analyses. Melting points and T_g values were obtained by DSC. Thermal decomposition data (5% weight loss temperature) were recorded by TGA. X-ray single-crystal structures show that 9 and 26 crystallize in monoclinic space group P2(1)/c.