Sydnones IV. Synthesis of Sydnones Analogous to the Photochromic Compounds

N-(6-methoxy-3-pyridyl)-sydnone (I), N-(4-nitrobenzyl)sydnone (II-1), and N-(2-nitrobenzyl)sydnone (II-2) have been prepared. Condensation of 2, 4-dinitrochlorohenzene with N-(carbethoxymethyl)sydnone (II-4) produced N-[(2, 4-dinitrophenyl) carbethoxymethyl]-sydnone (II-5). Under normal conditions none of them are photochromic.     

斯德酮与芳香胺的Mannich反应

3－（4－甲基苯甲酰基乙基）斯德酮和3－（3－羟基－3－苯基丙基）斯德酮 可以与芳香胺发生Mannich反应，得到斯德酮与芳香胺的Mannich碱。     

Acid induced reactions of a sydnone ketoxime

3-(2-Acetylphenyl)sydnone oxime 1a reacts with acids (methanesulfonic-, p-toluenesulfonic, trifluoroacetic-acid or Amberlite IR 118) to give products apparently derived from protonation of the oxime oxygen or nitrogen atom followed by cyclization to the sydnone ring or interception by water.     

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.     

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.     

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.     

Bromination of sydnones. I. Reaction with 3-arylsydnones containing electron-donors on the aryl ring

Bromination has been examined for a series of 3-arylsydnones (1) with electron donors (dimethyl to dimethoxy) on the aryl ring. In no example was exclusive aryl ring bromination observed, however, exclusive sydnone ring bromination could be realized in every case. For two dimethoxyphenyl examples both aryl and sydnone ring bromination occurred.     

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.     

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.     

Preparation of complexes of palladium chloride with di-tert-butylsydnonylphosphine and diphenylsydnonylphosphine and structural analysis of the sydnone ring containing phosphine and palladium complex

Three sydnonylphosphinepalladium(II) chloride were prepared. X-ray analyses of complexes of diphenylsydnonylphosphine with palladium chloride reveals that the sydnone ring contributes electrons through phosphorus to metal resulting in decreasing substantial bond lengths. By comparing the bond length of P---C(sydnone) and P---C(phenyl) suggests that phenyl rings are able to contribute more electrons to phosphorus for chelation leading to short P---C(phenyl) bond lengths.     

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.     

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.     

The mass spectra of sydnones

The mass spectra of thirty sydnoes have been interpreted; the types investigated include 3-aryl, 3-alkyl-, substituted 3-alkylsydnones; and bis sydnones. A characteristic fragmentation mode involves initial loss of NO and CO from the molecular ion, but peaks corresponding to alkylcarbonium ions dominate the spectra of 3-alkylsydnones; a cyclic mechanism is suggested for weak transitions involving loss of sydnone neutral molecule from the molecular ion. A mechanism is proposed for loss of chlorine radical from the molecular ion of 3-(2,4-dichlorophenethyl)sydnone. An unusual feature in the mass spectrum of trimethylenebis sydnone is rationalised on the basis of a precursor 1,2,3-oxadiazole ion. The effect of substituents in the aryl ring on the fragmentation of 3-arylsydnones is discussed.     

Cycloaddition reaction of sydnone and maleimide

The cycloaddition of sydnone to maleimide afforded exclusively two isomeric 1:2-adducts. This bifunctional character of sydnone allows its reaction with bismaleimides to form novel polyimides.     

Synthesis of N6-phosphorylated sydnone imines and their functionalization via 4-Li derivatives. Novel bicyclic sydnone imines

The highly efficient gram-scale method for preparation of up to date hardly available N₆-phosphorylated sydnone imines based on the reaction of sydnone imine hydrochlorides with substituted phosphinate or phosphonate acids chlorides in the presence of a base was elaborated. A possibility of straight deprotonation of sydnone imines with n-BuLi followed by the reaction 4-Li-derivatives thus obtained with electrophiles was demonstrated. Novel representatives of bicyclic sydnone imines fused via 4,5-edge of the oxadiazolium ring were obtained. Also sydnone imines containing both phosphorus and sulfur functionalities were obtained with high yields.     

Meso-ionic compounds. XI,photochromic 4-halogeno-3-(3-pyridyl)sydnones

Halogenation of 3-(3-pyridyl)sydnone with N-halosuccinimides in chloroform afforded the 4-halogeno-3-(3-pyridyl)sydnones where X = CI, Br, I. The 4-chloro- and 4-bromopyridylsydnones were photochromic. 3-(3-Pyridyl)sydnone was obtained in both high yield and purity by dehydration of N-nitroso-N-(3-pyridyl)glycine with trifluoroacetic anhydride.     

Discovery of new mutually orthogonal bioorthogonal cycloaddition pairs through computational screening

Density functional theory (DFT) calculations and experiments in tandem led to discoveries of new reactivities and selectivities involving bioorthogonal sydnone cycloadditions. Dibenzocyclooctyne derivatives (DIBAC and BARAC) were identified to be especially reactive dipolarophiles, which undergo the (3 + 2) cycloadditions with N-phenyl sydnone with the rate constant of up to 1.46 M^–1 s^–1. Most significantly, the sydnone-dibenzocyclooctyne and norbornene-tetrazine cycloadditions were predicted to be mutually orthogonal. This was validated experimentally and used for highly selective fluorescence labeling of two proteins simultaneously.     

Studies on the Syntheses of Sydnone Derivatives and Their Properties: XVI. Syntheses of 4-Sydnonyl Tosylates by Anodic Tosylation

As the first synthesis of sydnone derivatives having a carbon-oxygen bond at the 4-position of sydnone ring, 4-sydnonyl tosylate were successfully prepared by anodic substitution reaction.     

N6-tert-Butoxycarbonyl derivatives of sydnone imines: Preparation and synthetic use

A highly efficient gram-scale method for the C(4)-functionalization of sydnone imine hydrochloride derivatives was developed. This new approach was realized through consecutive reactions including the preparation of a C(3)-substituted N₆-tert-butoxycarbonyl sydnone imine derivative, deprotonation with n-BuLi and reaction of the lithiated-intermediate with an electrophilic agent, and removal of the Boc protecting group.     

Pariser-Parr-Pople SCF MO Calculation on the Sydnone Ring

The repulsive bond order of the sydnone ring between 2- and 4-positions is very high negative and the π-charge density carbon atom of position 4 is very small. The structure of sydnone ring are both dipolar form and mesoionic form.