Acetylation and Debromination of Sydnones Accelerated by Ultrasound

In the presence of a catalytic amount of 60% perchloric acid, 4-acetyl-3-substituted sydnones were obtained more conveniently with greater yields by the sonochemical reaction of 3-substituted sydnone with acetic anhydride. Some 4-acetylsydnones which are difficult to synthesize by a known process were obtained in 17-68% yields. 4-Bromo-3-(bromoaryl)sydnones with activated zinc powder dispersed in methanol were debrominated regioselectively by ultrasound in high yields (60-96%). 3-(2′-/4′-Amino-3′,5′-dibromophenyl)sydnone is synthesized easily from 3-(2′/4′-aminophenyl)sydnone by reduction, bromination and debromination subsequently.     

Synthesis and characterization of photolabile o-nitrobenzyl derivatives of urea

We present here the synthesis and characterization of four photolabile derivatives of urea in which alpha-substituted 2-nitrobenzyl groups are covalently attached to the urea nitrogen. These derivatives photolyze readily in aqueous solution to release free urea. The alpha-substituents of the 2-nitrobenzyl group strongly influence the rate of the photolysis reaction measured with transient absorption spectroscopy. Rates of photolysis at pH 7.5 and room temperature (approximately 22 degrees C) for N-(2-nitrobenzyl)urea, N-(alpha-methyl-2-nitrobenzyl)urea, N-(alpha-carboxymethyl-2-nitrobenzyl)urea, and N-(alpha-carboxy-2-nitrobenzyl)urea are, respectively, 1.7 x 10(4), 8.5 x 10(4), 4.0 x 10(4), and 1.1 x 10(5) s(-)(1). The quantum yields determined by measurement of free urea following irradiation by a single laser pulse at 308 nm were 0.81 for N-(2-nitrobenzyl)urea, 0.64 for N-(alpha-methyl-2-nitrobenzyl)urea, and 0.56 for N-(alpha-carboxy-2-nitrobenzyl)urea. The caged N-(alpha-carboxy-2-nitrobenzyl)urea is not a substrate of the enzyme urease, while the photolytically released urea is. Also, neither this caged urea nor its photolytic side products inhibit hydrolysis of free urea by urease. Thus, the alpha-carboxy-2-nitrobenzyl derivative of urea is suitable for mechanistic investigations of the enzyme urease.     

Polarography of non-benzenoid aromatic and related substances—VI Polarographic and spectrophotometric study of steric hindrance of coplanarity in 3-phenylsydnones

Substitution of alkyl groups on the ortho-position of 3-phenylsydnone causes a steric hindrance in coplanarity of the sydnone and phenyl rings. This was proved from the shift of the polarographic half-wave potentials (in excess of the polar effects), from the ultra-violet spectra, and from scale models. The behaviour of 3-o-tolylsydnone resembles more that of 3-benzylsydnone than that of 3-phenylsydnone. In 3′,4′-dihydroquinolino[1′,2′-c]-sydnone, the —CH₂ CH₂—bridge brings the sydnone and phenyl rings into a nearly coplanar position, shown on scale models, and its polarographic and spectrophotometric behaviour resembles that of 3-phenylsydnone.     

Sydnones as Masked Hydrazines for Heterocycle Formation: Reactions of 3-(2-substituted phenyl)sydnones with HCl

In general, reaction of 3-(2-substituted phenyl)sydnones with HCl gives products derived from cleavage of the sydnone ring to the corresponding hydrazine and subsequent cyclization to the side chain. In one case, 3-(2-aminophenyl)sydnone ( 43 ), the product obtained, l-amino-lH-benzimidazole ( 47 ), apparently results from nucleophilic interception by the side chain prior to complete cleavage of the sydnone ring.     

Sydnones and sydnone imines

For a number of sydnone imines with nonaryl substituents in position 3 the influence of structural factors on the kinetics of alkaline ring-opening has been studied and it has been found that the stability of the heterocycle falls with an increase in the electronegativity of the substituents. On passing from 3-aryl- to 3-nonaryl-substituted sydnone imines the mechanism of the reaction of alkaline ring-opening changes.For part XXXV, see [7].     

Studies on the Preparation and Biological Activities of 3-(O-Methoxybenzyl)Sydnone Derivatives and 3-(Fluorophenyl)Sydnones

Two new sydnones; 3-(o-methoxybenzyl)sydnone(1) and 3-(o-melhoxybenzyl)-4-morpholinomethylsydnone(2) were synthesized from o-methoxybenzylamine and ethyl bromoacetat in moderate yields. 3-(o-,m-,p-Fluorophenyl)sydnones were prepared from the corresponding fluoroaniline and chloroacetic acid in higher yields with a conventional method. From the biological activity test, 1 shows significant response of coronary dilation test, collagen induced platelet aggregation inhibition, local anesthetic and moderate cardiotropic activity. In addition, 1 also leads to anticonvuls, muscle relaxation and behavior depression. But 2 only shows inhibition of collagen induced platelet aggregation and antiwrithing. 3-(p-Fluorophenyl)sydnone (5) shows significant response of coronary dilation, collagen induced platelet aggregation inhibition, moderate cardiotropic activity, antiwrithing and local anesthetic But 3-(o-Fluorophenyl)sydnone(3) and 3-(m-fluorophenyl)sydnone(4) only show coronary dilation and moderate cardiotropic activity.     

Enantiospecific inclusion of chiral 1,2-dichloroethane rotamers in the crystal lattice of chiral square-pyramidal Cu(II) complexes with perfectly polar alignment of guest and host molecules

The inclusion compounds, [CuL(1)2(H2O)].(P)-C2H4Cl2 and [CuL(2)2(H2O)].(M)-C2H4Cl2(HL1 = N-(2-hydroxy-5-nitrobenzyl)-(R)-alpha-methylbenzylamine and HL2 = N-(2-hydroxy-5-nitrobenzyl)-(S)-alpha-methylbenzylamine), crystallise in the non-centrosymmetric space group C2; intermolecular hydrogen bonding leads to a perfectly polar alignment of both host and guest molecules with enantioselectivity.     

Dinuclear peroxo complexes of molybdenum(VI) containing Mannich base ligands

Dinuclear molybdenum(VI) peroxo complexes containing Mannich base ligands having formulae [Mo₂O₄(O₂)₂L-L(H₂O)₂] · H₂O [where L-L = N-[1-morpholinobenzyl] acetamide (MBA), N-[1-piperidinobenzyl] acetamide (PBA), N-[1-morpholino(-4-nitrobenzyl)] benzamide (MPNBB), N-[1-piperidino(-3-nitrobenzyl)] benzamide (PMNBB), N-[1-morpholino(-2-nitrobenzyl)] acetamide (MONBA), and N-[1-morpholino(-3-nitrobenzyl)] acetamide (MMNBA)] have been synthesized by stirring ammonium heptamolybdate with excess 30% aqueous hydrogen peroxide followed by treatment with ethanolic solution of corresponding ligands. The complexes have been characterized by elemental analysis, molar conductance, magnetic measurements, infrared (IR), electronic, TGA/DTA, mass spectral, and ¹H NMR studies. The complexes are non-electrolytes and diamagnetic. The IR spectral studies suggest that the ligands are bidentate to metal through carbonyl oxygen and ring nitrogen. Thermal analyses provide conclusive evidence for the presence of coordinated, as well as lattice water in the complexes. Dinuclear complexes preserve the individuality of the molybdenum oxo peroxo core. The complexes exhibit higher antibacterial activity against bacterium Ralastonia solanacearum (Pseudomonas solanacearum) than the free ligands.     

Improved Method for the Iodination of Sydnones

Iodination at the sydnone C-4 position has been achieved in good yields for a series of 3-arylsydnones using N-iodosuccinimide in acetic acid.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resources: Full experimental and spectral details.]     

Reduction of Acetylsydnones with Borohydride Anion: Preparation of 4-(1-Hydroxyethyl) Sydnones

Acetyl group on the sydnone ring can be reduced by using NaBH₄ in MeOH solution in good yields. Acetyl group on the sydnone ring is less reactive for reduction than that on a phenyl ring when both rings are present.     

A Facile One-Pot Synthesis of 4-Acyl and 4-(1-Hydroxyethyl)Sydnones

A series of 4-formyl-, 4-acetyl- and 4-(l'-hydroxyethyl)sydnones have been prepared in good yields by reaction of sydnone with butyllithium or a Grignard reagent and N,N-dimethylformamide, N,N-dimethylacetamide and acetylaldehyde, respectively.     

Synthesis, gastrointestinal prokinetic activity and structure-activity relationships of novel N-[[2-(dialkylamino)ethoxy]benzyl]benzamide derivatives.

Novel N-[[dialkylamino)ethoxy]benzyl]benzamide derivatives (II-1-51), derived from the structural modification of metoclopramide (I), were synthesized and examined for their pharmacological activities. Among them, N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide (II-34) which exhibited well balanced gastrointestinal prokinetic and antiemetic activities was selected as a new type of gastrointestinal prokinetic agent.     

Acylation of Sydnones with Acetic Anhydride in the Presence of Montmorillonite K-10

Various 4-acetyl sydnones 2 can be prepared in good yield by reaction of the corresponding 3-arylsydnones (cf. 1) with acetic anhydride at ～ 110°C catalyzed by Montmorillonite K-10. The reaction fails where an ortho-keto moiety is present; therein sydnone ring cleavage occurs to form the corresponding indazole 3.     

Antiferromagnetic FeIII6 ring and single-molecule magnet MnII3MnIII4 wheel

Reactions of a quadridentate ligand [N-(2-hydroxy-5-nitrobenzyl)iminodiethanol] with iron and manganese chloride in methanol yielded an antiferromagnetic FeIII6 ring and a single-molecule magnet MnII3MnIII4 wheel, respectively.     

The Structure of 3-Phenyl-4-(N-Carbamyl-1,4,2-Oxathiazolimin-3-yl)Sydnone,C11H7N5O4S·0.8 CH2Cl2

The title compound (M_r = 373) crystalizes in the othorhombic space group P bna with a = 10.410(2), b = 11.658(4), c = 23.108(3) Å, V = 2804.4 Å Z = 8. The single crystal intensity data were collected using MoK∞ radiation (λ = 0.7093Å) at room temperature. The crystal and molecular structure was solved with the final agreement index R = 0.039 for 1046 observed reflections. The bond lengths N(1)- C(7) and C(7)-C(8) of the title compound are slightly longer than those of 3-substituted sydnone derivatives. This may be attributed to the steric effect arising from the interaction of the phenyl ring and the 4-substituent with the neighboring atoms of sydnone ring. Both the title compound and 4-acetyl-3-(p-tolyl)sydnone have smaller dihedral angles between the sydnone ring and the plane of the sp² orbital of the double bond of the 4-substituent and both have shorter C(7)-C(9) bond lengths than those of other similar sydnone derivatives.     

Structure-optical property relationships in organometallic sydnones

As part of an effort to develop a spectroscopic structure-property relationship in platinum acetylide oligomers, we have prepared a series of mesoionic bidentate Pt(PBu3)2L2 compounds containing sydnone groups. The ligand is the series o-Syd-(C6H4-C[triple bond]C)n-H, where n = 1-3, designated as Syd-PEn-H. The terminal oligomer unit consists of a sydnone group ortho to the acetylene carbon. We synthesized the platinum complex (Syd-PEn-Pt), the unmodified ligands (PEn-H), and the unmodified platinum complexes (PEn-Pt). The compounds were characterized by various methods, including X-ray diffraction, 13C NMR, ground-state absorption, fluorescence, phosphorescence, and laser flash photolysis. From solving the structure of Syd-PE1-Pt, we find the angle between the sydnone group and the phenyl group is 45 degrees . By comparison of the 13C NMR spectra of the sydnone-containing ligands, the sydnone complexes with the corresponding unmodified ligands and complexes not containing the sydnone group, the sydnone group is shown to polarize the nearest acetylenes and have a charge-transfer interaction with the platinum center. Ground-state absorption spectra of the complexes in various solvents give evidence that the Syd-PE1-Pt complex has an excited state less polar than the ground state, while the PE1-Pt complex has an excited state more polar than the ground state. In all the higher complexes the excited state is more polar than the ground state. The phosphorescence spectrum of the Syd-PE1-Pt complex has an intense vibronic progression distinctly different from the PE1-Pt complex. The sydnone effect is small in Syd-PE2-Pt and negligible in Syd-PE3-Pt. From absorption and emission spectra, we measured the singlet-state energy E(S), the triplet-state energy E(T), and the singlet-triplet splitting Delta E(ST). By comparison with energies obtained from the unmodified complexes, attachment of the sydnone lowers E(S) by approximately 0.1 eV and raises E(T) by approximately 0.1 eV. As a result, the sydnone group lowers Delta E(ST) by approximately 0.2 eV. The trends suggest one of the triplet-state singly occupied molecular orbitals (SOMOs) is localized on the sydnone group, while the other SOMO resides on the rest of the ligand.     

Studies on the Synthesis of the Sydnone Derivatives and its Properties IV: The Diarylation of Sydnone Compound

In the presence of H₂SO₄, the sydnone rings were condensed with formaldehyde to give diarylation in 4-position of the sydnone rings: 3,3′-diphenyl-4,4′-methylenedisydnone is obtained from 3-phenylsydnone in 61% yield, and 3,3′-di-p-methylphenyl-4, 4′-methylenedisydnone is obtained from 3-(4′-methylphenyl)sydnone in 70% yield. And the possible reaction mechanism is discussed.     

Secondary metabolites of Pyricularia oryzae I. o-Nitrophenol derivatives

o-Nitrophenol derivatives have been isolated from the culture liquid of the deuteromycetePyricularia oryzae Cav.: 4-hydroxy-3-nitrophenylacetic acid, 4-hydroxy-3-nitrobenzyl alcohol, 1- and 2-(4-hydroxy-3-nitrophenyl(ethanols, N-(4-hydroxy-3-nitrophenylethyl)acetamide, and pyriculamide. This is the first time that any of these compounds has been isolated from natural sources. The o-nitrophenols obtained possess moderate growth-inhibiting activity in relation to rice shoots.     

A convenient route to N-[2-(Fmoc)aminoethyl]glycine esters and PNA oligomerization using a Bis-N-Boc nucleobase protecting group strategy

A simple and practical synthesis of the benzyl, allyl, and 4-nitrobenzyl esters of N-[2-(Fmoc)aminoethyl]glycine is described starting from the known N-(2-aminoethyl)glycine. These esters are stored as stable hydrochloride salts and were used in the synthesis of peptide nucleic acid monomers possessing bis-N-Boc-protected nucleobase moieties on the exocyclic amino groups of ethyl cytosin-1-ylacetate, ethyl adenin-9-ylacetate and ethyl (O(6)-benzylguanin-9-yl)acetate. Upon ester hydrolysis, the corresponding nucleobase acetic acids were coupled to N-[2-(Fmoc)aminoethyl]glycine benzyl ester or to N-[2-(Fmoc)aminoethyl]glycine allyl ester in order to retain the O(6) benzyl ether protecting group of guanine. The Fmoc/bis-N-Boc-protected monomers were successfully used in the Fmoc-mediated solid-phase peptide synthesis of mixed sequence 10-mer PNA oligomers and are shown to be a viable alternative to the currently most widely used Fmoc/Bhoc-protected peptide nucleic acid monomers.     

Cycloadditions of anionic N-heterocyclic carbenes of sydnone imines

Sydnone imines were deprotonated with lithium bis(trimethylsilyl)amide at the C4 position to give the corresponding sydnone imine anions as lithium adducts. These can be represented as lithium stabilized anionic N-heterocyclic carbenes. Treatment with diisopropyl azodicarboxylate (DIAD) gave the corresponding C4 adducts, i.e. 4-hydrazinyl-sydnone imines, which form tautomers in solution. Reductive 1,3-dipolar cycloadditions of the sydnone imine anions with tetracyanoethylene (TCNE) resulted in the formation of pyrazoles, the mechanism of formation of which differs from known reactions. Reaction of the anion derived from the 2-methoxyphenyl sydnone imine with N,N-diisopropylcarbodiimide gave a ring-cleaved bisiminonitrile. Structure elucidations were accomplished by NMR spectroscopy and by four single crystal X-ray analyses.