4‐Methyl‐ and 4‐(Halophenyl)pyrimidinium (4‐Halobenzoyl)methylides. Correlation of Structure,Stability, Reactivity,and Biological Activity

For the first time in the cycloimminium ylide series, we present a theoretical and experimental study concerning the correlation between structure, stability, reactivity, and biological activity of 4‐(R)‐pyrimidinium (4‐halobenzoyl)methylides (R = Me and 4‐chlorophenyl; hal = X = F, Cl, Br, I; see 5 and 6 in Scheme 1). The 4‐methylpyrimidinium (4‐halobenzoyl)methylides 5 are relatively stable compounds, while the (4‐chlorophenyl)pyrimidinium (4‐halobenzoyl)methylides 6 are more unstable. Their stability varies with the nature of the substituents at the ylide carbanion and pyrimidinium cation moieties as confirmed by quantum‐chemical calculations. The latter also disclose the possibility to use pyrimidinium ylides as nucleophilic reagents as well as 1,3‐dipoles in reactions with appropriate reagents. The experimental data obtained confirm the calculations concerning the nucleophilicity and reactivity of the ylides 5 and 6 . Moreover, the influence of microwave irradiation on the synthesis of the pyrimidinium salts 3 and 4 from pyrimidine and an organic halide is studied and reveals a remarkable reaction‐rate increase under microwave irradiation as compared to classical conditions; this allows the general and facile synthesis of the salts 3 and 4 (Scheme 1, Table 1). The in vitro biological activity of the newly obtained 4‐methylpyrimidine compounds is also tested. Some of them exhibit a remarkable activity against different microorganisms (germs and fungi) which allows to establish structure–activity correlations.     

VICARIOUS NUCLEOPHILIC SUBSTITUTION WITH SULFUR CONTAINING CARBANIONS

Abstract

Carbanions stabilized with sulfur containing substituents are versatile intermedi-ates in organic synthesis. The great value and importance of such carbanions is connected with specific properties of the sulfur atom which is capable to exist in a variety of valent states and to form many functional groups. These various sulfur-containing groups exert different carbanion stabilizing effects and can also serve as leaving groups in nucleophilic substitution or elimination reactions. Taking into account numerous types of sulfur containing functional groups and a variety of reactions they can promote, it is well understandable that reactions of sulfur-containing carbanions have been thoroughly studied and widely exploited in organic synthesis. The reactions of such carbanions with aliphatic electrophilic partners: alkylating agents, carbonyl compounds and Michael acceptors consist a major section of this field and were subject of numerous studies as well as many monographs.¹ Contrary to that, not very much was known about reactions of such carbanions with electrophilic aromatic compounds. Actually, there are only few reports on nitroarylation of sulfur-containing carbanions via replacement of halogen orfho- or para- to the nitro group in halonitrocornpounds.² There are also some reports on the alkylation of nitroarenes and heterocyclic compounds in the reaction with sulfonium3 and sulfoxonium4 ylides, dimethylsulfoxide carbanion,⁵ and dialkyl or alkyl aryl sulfones carbanions.⁶     

Etude des reactions des diazoderives avec les cycloimmonium ylures-I : Action des sels de diazonium sur quelques pyridinium - ylures

The synthesis of cycloimmonium salts of the type $\text{7}$, $\text{8}$ and the corresponding cycloimmonium ylides $\text{9}$, $\text{10}$ are reported. In the reaction with diazonium salts $\text{11}$, $\text{12}$ the pyridinium monosubstituted carbanion ylides $\text{9}$, $\text{10}$ give the pyridinium disubstituted carbanion ylides $\text{17}$ – $\text{20}$. These are new types of isolable stable ylides. The synthesis involves the formation “in situ” of ylides $\text{9}$, $\text{10}$ which are bonded by their nucleophile ylide carbon atom to the nitrogen atom in diazonium salts. The intermediat formation of cycloimmonium salts $\text{13}$ – $\text{16}$ must be accepted. The structures of all compounds presented in this paper have been established by using elementary analysis, IR and ¹H-RMN spectra.     

A monomeric gold(I) carbanion complex with an uncoordinated thioether: [2‐(methylsulfanyl)phenyl](triphenylphosphine)gold(I)

The title compound, [Au(C₇H₇S)(C₁₈H₁₅P)], is conformationally chiral and crystallizes from benzene–hexane as individually enantiopure crystals. This mononuclear compound has the Au^I atom linearly bound to a triphenylphosphine P atom and to a phenyl C atom of a 2‐(methylsulfanyl)phenyl group. The angle at the Au^I atom is 175.9 (2)°. The linear ligand coordination about the Au^I atom has geometric parameters inside the remarkably narrow range found for gold complexes bound by a phosphine ligand and by the ortho‐C atom of a substituted phenyl group. This is the first example of gold(I) attached to a methylsulfanyl aromatic carbanion.     

Intramolekulare Cycloadditionen Mit Azomethin-Yliden: Synthese und NMR-Untersuchungen einiger Paracyclophan-Derivate vom Makrolid-Typ

Intramolecular Cycloaddition Reactions with Azomethine Ylides: Synthesis and NMR Investigations of Some Macrolide-Type Paracyclophanes Several aziridine derivatives bearing a para-substituted phenyl group have been prepared as precursors of azomethine ylides for intramolecular 1,3-dipolar cycloadditions. Upon heating in refluxing toluene, the expected reactions take place resulting in the regioselective formations of the pairs of diastereoisomers 14 / 15 and 16 / 17 , respectively. As indicated by the sharply decreasing yield in the a -series (< 5%), a useful application of this method for preparing paracyclophane compounds is restricted to derivatives with more than 11 bridging atoms. The results of detailed ¹H- and ¹³C-NMR investigations with the pyrrolidino-annulated cyclophanes are discussed with respect to the configuration at the five-membered heterocycles and to the conformational flexibility of the bridges.     

Rhodium(II)-catalyzed addition of 2-diazo(fluoroalkyl)acetoacetates to sulfides: a simple synthesis of stable sulfonium ylides

2-Diazo(fluoroalkyl)acetoacetates 1 reacted readily with many sulfides under mild reaction conditions in the presence of catalytic Rh₂(OAc)₄ affording to the corresponding sulfonium ylides. While thianthrene gave trans-thianthrenium 5,10-di(fluoroalkylacetoethoxycarbonyl)methylides (7a and 7b) under the same reaction condition, the structure of 7btrans-thianthrenium 5,10-di(bromodifluoroacetoethoxy-carbonyl)methylides was fully confirmed by spectral methods and X-ray single crystal diffraction analysis. All the ylide products obtained are fairly stable due to the strong electron-withdrawing properties of the fluorine atom.     

Electron-impact-induced rearrangements in the mass spectra of phosphinyl stabilized triphenylphosphonium ylides

Examination of the mass spectra of some methyl and phenyl phosphonate stabilized triphenylphosphonium ylides revealed that these compounds are quite stable to electron-impact and provided valuable structural information. They exhibit strong molecular and [M - H]⁺ ions, and fragment ions which are characteristic for the phosphonium or the phosphonate portion of the molecules. Numerous rearrangement ions were detected, however, the most prominent of which involves the migration of a phosphonate phenyl to the ylide carbon, leading to the base peak (m/e 352) in the spectrum of diphenyl triphenylphosphoranylidenemethylphosphonate. The mechanism of these fragmentations has been studied with the aid of high resolution analysis and deuterium labeled analogs whose preparation is reported.     

CNDO/2-CALCULATIONS ON THE STABILIZATION OF CARBANIONS BY σ-BIVALENT SULFUR

Abstract

The significantly enhanced acidity of C[sbnd]H bonds attached to a σ-bivalent sulfur atom can be explained without taking into account the octet expansion of sulfur. The higher carbanion stabilization effect of sulfur in comparison to oxygen has been related to the greater capability of the σ-bivalent sulfur to take up excess charge into the sp-valence shell.     

Catalytic Asymmetric [2, 3]－Sigmatropic Rearrangement of Sulfur Ylides Generated from Carbenoids and Allenic 2－Methylphenyl Sulfide

The first investigation on catalytic asymmetric [2,3]-sigmatropic rearrangement of sulfur ylides generated from carbenoids and allenic phenyl sulfide was carried out. Up to 55% ee value was obtained.     

Non-selectivity in the reaction of levoglucosenone with the sulfinyl allyl carbanion

Condensation of levoglucosenone with the carbanion ofrac-allyl phenyl sulfoxide, in contrast with reactions of this anion with the majority of other unsaturated ketones, proceeds without regio- or enantioselectivity to give a (1.0–1.8): 1 mixture of products of both 1,2- and 1,4-γ-addition of the allylic residue. Each product is a (1.2–1.6): 1 mixture of epimers at the asymmetric sulfur atom. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 157–159, January, 1999.     

Photochemische Synthesen potentiell hypoglykämisch wirkender 3-Oxazoline

Photochemical Syntheses of 3-Oxazolines which Possibly Exhibit Hypoglycemic Activity Reactions of photochemically generated benzonitrile methylides 2 with carbonyl compounds 3 yielded 3-oxazolines of the types 5 and 6 (Scheme 1). Photooxidation of 5-[p-(dimethylamino)phenyl]-2,2-dimethyl-4-phenyl-3-oxazoline ( 5a ) gave 4′-(2,2-dimethyl-4-phenyl-3-oxazolin-5-yl)-N-methylformanilide ( 6r ) which could be transformed to 2,2-dimethyl-5-[p-(methylamino)phenyl]-4-phenyl-3-oxazoline ( 6s ) by photodecarbonylation. Thirty 3-oxazolines of types 5 and 6 have been synthesized and tested by oral and/or intraperitoneal administration to starved rats and obese-hyperglycemic mice.     

Synthesis and properties of novel pyrazolopyrimidine derivatives containing sulfur atom

A series of new pyrazolopyrimidine derivatives containing sulfur atom 5 has been designed and synthesized by treatment of carbodiimide 3 , which came from iminophosphorane 2 undergoing a aza‐Wittig reaction with phenyl ioscyanate, with alkylamine. The structures of compounds 5 were confirmed by ¹H NMR, IR, EI‐mass spectroscopy, and elemental analysis. The results of preliminary bioassay indicate that most compounds 5 exhibit an inhibition effect against Cercospora beticola, Botryosphaeria berengeriana, and Pellicularia sasakii, and compound 5g shows 91.2% inhibitory rate to root of rape and the other less than 50% at 100 mg/l. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:333–337, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20024     

Pyramidalization at the sp2-Hybridized ipso-Carbon Atom of Phenyl Compounds

In this study we investigate the pyramidalization of the sp²-hybridized center at the ipso-carbon atom C_i of phenyl compounds on the theoretical side by DFT calculations of toluene, t-butylbenzene, and ethylbenzene and on the experimental side by a scatter plot analysis of 14,169 structures of ethylbenzene compounds C_β−C_αH₂−C₆H₅ with three open positions for variation at C_β, accumulated in the Cambridge Structural Database. In a 360° rotation about the bond between C_α of the substituent and the ipso-carbon atom C_i of the phenyl ring, the pyramidalization performs three maxima and minima. A comparison of structures with pyramidalization and its hypothetical counterparts without pyramidalization shows that pyramidalization is associated with a gain of energy. The data reveal that it is the carbon atom C_α of the phenyl substituent, which on pyramidalization bends away from the phenyl plane. Pyramidalization of sp²-hybridized centers is an omnipresent member in molecular weak interactions.     

Stereoelectronic Properties,Stereospecificity and Stabilization of α-Seleno Carbanions. An ab initio Study

An ab initio study of α-seleno carbanions show that they are subject to appreciable polarization and stereoelectronic effects. Like in α-thia carbanions, the equatorial e forms are more stable than the axial a forms, one of the stabilizing contributions being the conformation dependent (C-lone pair, σ* Se? Z) interaction. The carbanion stabilizing effect of the α-Se atom is about 3 kcal/mol larger than that of the sulfur analog. As in the case of the sulfur no specific effect of the d orbitals is found.     

Structure of dicyano-pyridinium methylide and amidocyano-pyridinium methylide using ab initio and semi-empirical methods

Taking into account the X-ray diffraction patterns of dicyano-pyridinium methylide and amidocyano-pyridinium methylide, comparative ab initio and semi-empirical studies have been performed. The aim of this study is to elucidate some electronic and structural properties of the cycloimmonium ylides. In fact, we found that the positive charge of the ylide nitrogen atom is delocalized on the pyridine ring. The ylide carbon atom is found to be insignificantly charged. This proves that the formal negative charge often accepted for the ylidic carbanion is delocalized. Thus, we demonstrate the existence of the resonance interaction between the ylidic carbanion and the positive aromatic ring as a factor of stability for planar cycloimmonium ylides. The negative charges found for the cyclic carbon atoms adjacent to the ylide nitrogen atom precludes any nucleophilic addition on the α carbon atoms in the heterocyclic ring. This is in good agreement with the experiments, where no nucleophilic addition on such atoms has ever been observed. Among the six semi-empirical methods used in this paper, the AM1 method is the most appropriate in the study of planar cycloimmonium ylides. This method is found to reproduce the experimental values and ab initio results with good accuracy.     

Sulfur ylides

The mass spectra of negative ions of keto-stabilized sulfur and phosphorus ylides (obtained from amino acids) and products of their thermal conversion are studied. The most characteristic peaks in the mass spectra of ylides belong to negative molecular ions and to [M−H]⁻ ions. Peaks of fragment ions in the mass spectra of ylides and products of their thermal conversion coincide both in mass numbers and resonance energies. For Part 8, see Ref. 1. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2100–2103, November, 1999.     

Stereoselective Cyclopropanation of 2‐[(S)‐(4‐Methylphenyl)sulfinyl]cyclopent‐2‐en‐1‐one with Sulfur Ylides and α‐Halo Carbanions. Preliminary Communication

The cyclopropanation of the title compound (S)‐ 2 with various sulfur ylides has been examined. The reaction with methylenesulfonium ylides gave the corresponding cyclopropanes 4 with low diastereoselectivity. The formation of the second product 5 arising from the subsequent methylenation of the CO group was also observed. A clean cyclopropanation of (S)‐ 2 took place with ethyl (dimethylsulfanylidene)acetate affording the cyclopropanes 6 , with high π‐facial selectivity, but low endo/exo ratio. A high endo/exo selectivity, but low π‐facial selectivity was observed in the reaction of (S)‐ 2 with (2‐ethoxy‐2‐oxoethyl)(diphenyl)sulfonium tetrafluoroborate. The use of α‐bromoacetate carbanion as the cyclopropanation reagent resulted in the formation of 6 with very high facial and endo/exo‐selectivity. In a proposed explanation of the stereochemical outcome of the cyclopropanations investigated, the ground‐state conformation of the sulfoxide 2 and the transition‐state structure of the initial addition step were taken into account.     

Gold-Catalyzed Cycloisomerization of Sulfur Ylides to Dihydrobenzothiepines

The metal-promoted nucleophilic addition of sulfur ylides to π-systems is a well-established reactivity. However, the driving force of such transformations, elimination of a sulfide moiety, entails stoichiometric byproducts making them unfavorable in terms of atom economy. In this work, a new take on sulfur ylide chemistry is reported, an atom-economical gold(I)-catalyzed synthesis of dihydrobenzo[b]thiepines. The reaction proceeds under mild conditions at room temperature.     

Protonenresonanzuntersuchungen an Aminoboranen—II: Einflüsse von para-Phenylsubstituenten auf die Rotationsbarriere um die N?B-Bindung

The electronic influence of substituents on the free enthalpy of rotation around the N? B bond in aminoboranes was investigated in two series of compounds: (a) (CH₃)₂N?BCl (phenyl-p-X), containing the para-phenyl substituent at the boron atom, and (b) (p-X-phenyl)CH₃N?B(CH₃)₂, containing the para-phenyl substituent at the nitrogen atom of the N? B linkage (X = ? NR₂, ? OCH₃, ? C(CH₃)₃, ? Si(CH₃)₃, ? H, ? F, ? Cl, ? Br, ? I, ? CF₃ and ? NO₂). By comparing the rotational barriers in corresponding compounds of both series, a reverse effect of the substituents could be observed. Electron-withdrawing substituents in the para position of the phenyl ring increase the ΔG_c^≠ if the phenyl group is attached to the boron atom; on the other hand, a lower ΔG_c^≠ is observed if the phenyl ring is bonded to the nitrogen atom of the N? B system. Substitution of the phenyl ring with electron-donating substituents in the paraposition exerts the opposite effect. Within each series of compounds, the differences of ΔG_c^≠ values [δ(ΔG_c^≠) = ΔG_c^≠ (X) ? ΔG_c^≠ (X = H)] between substituted and unsubstituted compounds can be explained in terms of inductive and mesomeric effects of the ring substituents and can be correlated with the Hammett σ constant of each substituent. A comparison of the slopes of the plotted lines shows that the influence of the ring substituents is more pronounced in compounds with N-phenyl-p-X than in those with B-phenyl-p-X.     

Insight into vulcanization mechanism of novel binary accelerators for natural rubber

A novel TU derivative, N-phenyl-N′-(у-triethoxysilane)-propyl thiourea(STU), is prepared and its binary accelerator system is investigated in detail. Compared to the control references, the optimum curing time of NR compounds with STU is the shortest, indicating a more nucleophilic reaction occurs. The Py-GC/MS results present that the phenyl isothiocyanate fragment still remains in the NR/STU compounds with or without extracting treatment, but no silane segment can be found in the vulcanizate with extracting treatment. Vibrations of C=S, NH and aromatic ring in FTIR experiments and a new methyne carbon peak, as well as the peaks of phenyl group of STU, in the solid state 13C-NMR experiments are found in the NR/STU vulcanizate with extracting treatment. Moreover, the crosslinking density of vulcanizates with STU evolves to lower level, indicating the sulfur atom of STU does not contribute to the sulfur crosslinking. Therefore, a new vulcanization kinetic mechanism of STU is propounded that the thiourea groups can graft to the rubber main chains as pendant groups by chemical bonds during the vulcanization process, which is in accordance with the experimental observations quite well.