Acylation of diethyl (ethoxycarbonylfuryl)methanephosphonates under the conditions of claisen reaction

O,O-Diethyl (ethoxycarbonylfuryl)methanephosphonates are formylated with ethyl formate in the presence of sodium foil at the methylene group adjacent to phosphorus atom to form sodium salts of phosphonoacetic aldehyde. When the substituents in the furan ring are remote from one another, and also in the case of 3, 4-disubstituted isomer these salts in DMSO solution exist in the carbanion form. Anions of salts of (2-ethoxycarbonylfur-3-yl)phosphonoacetic aldehyde and the isomer with the reversed location of substituents in DMSO solution take part in the dynamic equilibrium between the carbanion and the enolate form. The alkylation of all salts obtained with allyl bromide and dimethyl sulfate proceeds exclusively at the oxygen to form a mixture of Z- and E-isomers of phosphorylated vinyl ethers.     

An asymmetric route to total synthesis of the furano lignan (+)-veraguensin

Total synthesis of the furano lignan (+)-veraguensin is described. The key steps involve a diastereoselective aldol-type condensation of an ester enolate having an α-chiral center with an aromatic aldehyde and a novel isomerization of the syn vicinal substituents on the furan ring via a ring opening-ring closing protocol.     

Aminophosphonocarboxylates of the Furan Series

Halomethyl derivatives of (diethoxyphosphorylmethyl)furan-2(3)-carboxylates containing blocking methyl group in the position 5 of the furan ring were synthesized. In the course of constructing of carbon skeleton of these compounds it was found that alkyl 3-methoxymethyl-, 3-chloromethyl-, and 3-(diethoxyphosphorylmethyl)-5-methyl-2-furoates are halomethylated at elevated temperature in the position 4 of the furan ring. No ring destructure or transformation of the side chain of substituents was observed. The obtained halomethylfurans and their tert-butyl analogs by treating with sodium azide in acetonitrile were converted to corresponding azides. The reduction of latter with triphenylphosphine in ethanol led to formerly unavailable aminophosphonocarboxylates of the furan series.     

Investigation of 2,5-disubstituted silylfurans by PMR spectroscopy

The¹H,¹³C, and²⁹Si NMR spectra of S-substituted furfurals and the corresponding diethyl acetals containing various alkylsilyl substituents at position S of the furan ring were studied in comparison with the carbon- and sulfur-containing analogs and also with a series of monosubstituted silylfurans. In cases where the substituent was conjugated with the residue of the furan molecule the effect of the substituent at position S of the furan was transmitted to C of the aldehyde group. The reverse effect was also observed. It was determined that the contribution from the aldehyde group and the substituents at position S of the furan to the screening of the carbon nuclei of the furan ring was not additive.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 449457, April, 1996.     

Pyramidal Inversion in Cyclic Sulfonium Salts

5- and 6-membered cyclic sulfonium salts carrying methyl substituents on the ring have been synthetized and partially resolved. These salts undergo thermal stereomutation at rates which are 10³ times lower than that of non-cyclic sulfonium cations. Very stringent evidence is presented that racemisation or, where the case may be, epimerisation takes place by pyramidal inversion of the sulfur atom.     

The formation and molecular structure of acetylcyclopentadienylsodium-tetrahydrofuranate

Acetylcyclopentadienylsodium has been isolated in crystalline form as a THF adduct from a reaction between cyclopentadienylsodium and methyl acetate in THF solution. The product has been characterized by means of a single-crystal X-ray diffraction study. {[C₅H₄CMeO]Na·THF}_n crystallizes in the monoclinic space group P2₁/c with unit cell parameters a 6.698(3), b 16.095(4), c 10.661(3) Å, β 92.93(3)° and D_c 1.17 g cm^?3 for Z = 4. Least-squares refinement led to a final R value of 0.080 based on 661 independent observed reflections. The coordination sphere around each sodium atom consists of the oxygen atoms from two C₅H₄CMeO ligands, the oxygen atom of the THF molecule, and an ion contact pair between the sodium and the five ring carbon atoms of the C₅H₄CMeO ligand.     

Reaction of 2- and 3-furylmethanephosphonates with esters

2- and 3-furylmethanephosphonates are acylated with ethyl formate, diethyl oxalate, and ethyl trifluoroacetate in toluene in the presence of sodium foil to afford five phosphorylated derivatives of furylacetic aldehyde, furylpyruvic acid, and 1,1,1-trifluoro-1-(2-furyl)propan-2-one. In a chloroform solution these compounds exist in the equilibrium with their enolic forms. When treated with sodium ethylate they form sodium salts which were isolated and characterized by ¹H, ¹³C, and ³¹P NMR spectroscopy. It was shown that in DMSO solutions sodium salts of formyl and oxalyl derivatives of 2-furylmethanephosphonate exist as mixtures of the carbanion and enolate forms. In the first case the carbanion form is predominant, while in the second one the enolate forms prevail. Sodium salt of formylated 3-furylmetanephosphonate exists only in the carbanion form, while the salt of 3-furylpyruvate is enolate. The alkylation of these salts with iodomethane proceeds at the carbon atom as well as at the oxygen one. First reaction pathway is often preferred.     

Ab initio study of mechanism of forming a spiro-heterocyclic ring compound involving Si from dichlorosilylenesilylene (Cl2Si=Si:)→Cl2Si=Si: and aldehyde

The mechanism of the cycloaddition reaction between singlet dichlorosilylenesilylene (Cl₂Si=Si:)→Cl₂Si=Si: and aldehyde has been investigated with the CCSD(T)//MP2/6-31G* method. From the potential energy profile, it could be predicted that the reaction has one dominant reaction pathway. The reaction rules presented is that the two reactants firstly form a four-membered ring silylene through the [2+2] cycloaddition reaction. Because of the 3p unoccupied orbital of Si: atom in the four-membered ring silylene and the π orbital of aldehyde forming a π → p donor–acceptor bond, the four-membered ring silylene further combines with aldehyde to form an intermediate. Because the Si: atom in the intermediate happens sp ³ hybridization after transition state, then the intermediate isomerizes to a spiro-heterocyclic ring compound involving Si via a transition state.     

Synthesis of furan 4′-thio-C-nucleosides, their methylsulfonium and sulfoxide derivatives. Evaluation as glycosidase inhibitors

A series of furan C-nucleosides having a sulfur atom in the sugar ring were synthesised. The α and β anomers of 3-ethoxycarbonyl-2-methyl-5-(4′-thio-d-erythrofuranosyl)furans 10 and 11 were obtained by acid treatment of (4′-S-acetyl-4′-thio-d-arabino-tetritol-1-yl)furan 9. Oxidation of 10 with m-chloroperbenzoic acid gave sulfoxide 12 as one epimer at the sulfur atom whereas 11 was transformed into sulfoxide 13 as an epimeric mixture. S-Methylation of 10 and 11 with methyl triflate led to sulfonium salts 14 and 15. The prepared compounds were found to be moderate inhibitors of α-l-fucosidase.     

Unexpected course of rearrangement of substituted S-(1(3H)-isobenzofuranone-3-yl)isothiuronium bromides

Three series of S-(1(3H)-isobenzofuranone-3-yl)isothiuronium bromides differing in substitution at the isothiuronium moiety (none, one or two methyl groups) and at the benzene ring were prepared and characterized. These salts were then treated with various bases (acetate, triethylamine, Na₂CO₃) to give either 1-hydroxy-3-oxo-1,3-dihydro-2H-isoindol-2-carbothioamides or the product of S to N isobenzofuranone-3-yl migration, i.e., 1,3-dimethyl-1-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)thioureas. If ammonia was used in reaction with N,N′-dimethyl isothiuronium salts then 3-hydroxy-2,3-dihydro-1H-isoindol-1-ones were formed together with 1,3-dimethyl-1-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)thioureas in parallel reaction with the yields increasing with ammonia concentration. The formation of isoindolones takes place in two steps with an aldehyde intermediate, which can be trapped with N,N-dimethylhydrazine.     

Mass-spectrometric study of 4-azaphenanthrene derivatives

The mass spectra of 15 compounds of the 4-azaphenanthrene series and their deutero analogs with bulky R substituents (R=-CCPh, -CH=CHPh, CHBr-CHBrPh,-CH=CHC₆H₄OCH₃-p, -COOH, -COOC₂H₅, and -CONHNH₂) in the ortho position relative to the nitrogen atom were studied. An intense [M-H]⁺ ion peak, the appearance of which is evidently due to a process involving cyclization of the carbon atom of the side chain with the nitrogen atom, is formed in the fragmentation of the styryl derivatives. The fragmentation of the compounds with a methyl group in the ortho position relative to the styryl grouping is accompanied by the formation of an intense [M-Ph]⁺ ion peak. An ortho effect of the carboxyl and carbethoxy groups adjacent to the methyl substituent is observed in the mass spectra of the investigated compounds. The data obtained make it possible to establish the structures of bulky substituents in the ortho position relative to the ring nitrogen atom and the position of the methyl group in the pyridine ring of monomethylated azaphenahthrenes.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 659–665, May, 1979.     

Solution fluxionality of some pyridine-2,6-dialdehydes, -diketones and -diesters when acting as bidentate ligands in rhenium(I) and platinum(IV) complexes. Crystal structure of [ReBr(CO)3L] (L=methylethyldipicolinate)

2,6-Disubstituted pyridines, where the substituents are aldehyde, ketone or ester functions, form bidentate chelate complexes with the transition metal moieties fac-Re^IX(CO)₃ (X=halogen). 2-Substituted pyridines, where the substituents are aldehyde or ester functions, form similar types of complexes with the isoelectronic transition metal moieties fac-Re^IX(CO)₃ and Pt^IVXMe₃. The fac-Re^IX(CO)₃ complexes of the 2,6-disubstituted pyridine ligands were shown by ¹H NMR spectra to undergo metallotropic shifts whereby the Re coordination switches between adjacent ON pairs of the ONO ligand donor set. Rates and activation energies of these fluxional shifts were measured by dynamic NMR bandshape analysis. Magnitudes of ΔG³ (298.15 K) were in the range 59–64 kJ mol⁻¹ for the diketone and diester ligands. The dialdehyde ligand, 2,6-pyridinedicarboxaldehyde, formed an appreciably less-stable Re^I complex that was highly fluxional and showed a tendency to dissociation at ambient solution temperatures. The unsymmetrical diester ligand, methylethyldipicolinate, formed two distinct Re^I complex species in solution, in the approximate abundance ratio of 2:1, the more abundant structure involving coordination to the carbonyl of the ethyl ester function. This particular complex forms exclusively in the solid state and an X-ray crystal structure of [ReBr(CO)₃L] (L=methylethyldipicolinate) is reported.     

Reaction of N-arylcarbamoyl-1,4-benzoquinone imines with sodium arenesulfinates

N-Arylcarbamoyl-1,4-benzoquinone imines possessing at least one free ortho position with respect to the carbonyl carbon atom in the quinoid ring react with sodium arenesulfinates according to the nucleophilic 1,4-addition pattern with complete regioselectivity. If both ortho positions are occupied, the reaction gives a mixture of products where the major ones are 1,6- and 6,1-adducts formed according to the radical ion mechanism.     

Different specificities in the bromination of 6-(2-furyl)imidazo[2,1-b]thiazole and its derivatives with 1 mole of bromine

The action of 1 mole of bromine on 6-(2′-furyl)imidazo[2,1-b]thiazole, its 2-methyl-, 3-methyl-, and 2,3-dimethyl-substituted derivatives, and their hydrobromides in chloroform and glacial acetic acid was studied. The bromination of bases containing a methyl group in the 3 position leads primarily to the 5′-derivatives with respect to the furan ring in chloroform, whereas in the remaining cases 5-bromo derivatives with respect to the imidazothiazole system are formed. Compounds of the latter type are formed by the action of bromine in glacial acetic acid or of sodium hypobromite in alkaline media on the bases. The hydrobromides are brominated in both acetic acid and chloroform, regardless of the substituents in the thiazole ring, primarily in the 5′ position of the furan ring. The structures of the bromination products were proved by means of alternative syntheses, thin-layer chromatography, and the PMR spectra.     

Transformation of methyl N-methyl-N-(6-substituted-5-nitro-4-pyrimidinyl)aminoacetates into 4-methylamino-5-nitrosopyrimidines and 9-methylpurin-8-ones

N-Methyl-N-(6-substituted-5-nitro-4-pyrimidinyl)aminoacetic acid methyl esters under the treatment of sodium alkoxides, depending on the nature of substituents in 6 position of the pyrimidine ring, undergo ring closure and rearrangement to give 6-substituted-4-methylamino-5-nitrosopyrimidines or 9-methylpurin-8-ones.     

Synthesis and selected reactions of ethyl 5-(1-chloroethyl)-2-methylfuran-3-carboxylate

Ethyl 2-methylfuran-3-carboxylate is smoothly chloroethylated at 0°C in the 5 position of the ring. The resulting halide alkylates secondary amines but eliminates HCl with sodium diethyl phosphite under the Michaelis-Becker reaction conditions and with trimethyl phosphite under the Arbuzov reaction conditions. In the reaction with sodium diethyl phosphite, small amounts of 5-[1-(diethoxyphosphoryl)ethyl]furan-3-carboxylate and 5-ethylfuran-3-carboxylate are formed. In the Arbuzov reaction at a 1: 1.22 furan: trimethyl phosphite molar ratio, methyl 2,4-dimethyl-1-methoxy-1-oxo-1λ⁵-1,2-dihydrophospheto[3,2-b]furan-5-carboxylate was isolated.     

Comparison of the electronic and steric structures of 1-vinyl-and 1-(prop-1-en-1-yl)pyrroles according to the <Superscript>1</Superscript>H and <Superscript>13</Superscript>C NMR data

According to the ¹H and ¹³C NMR data, 1-isopropenylpyrroles are characterized by larger dihedral angles between the heteroring and exocyclic double bond planes, as compared to isostructural 1-vinylpyrroles, due to steric effect of the α-methyl group in the propenyl fragment. As a result, p-π conjugation with the propenyl group is weaker than with the vinyl group. The propenyl group in 1-isopropenylpyrrole having no other substituents in the heteroring is forced out from the heteroring plane, while the 1-vinylpyrrole molecule is planar. If substituents are present in positions 2 and 5 of the pyrrole ring, the propenyl group on the nitrogen atom becomes orthogonal with respect to the pyrrole ring plane, so that no p-π conjugation is possible. The steric structures of (E)-1-(prop-1-en-1-yl)pyrrole and (Z)-1-(prop-1-en-1-yl)pyrrole are different: the propenyl group in the former is turned relative to the heteroring plane, while the latter molecule is planar.     

Structure and properties of lithium n-butyl amidinates

Lithium n-butyl amidinates (formally lithium salts of N',N-disubstituted amidoimides of pentanoic acid) with various substituents were prepared and characterized in solution by ¹H, ⁷Li, ¹³C and ¹⁵N NMR spectra parameters in C₆D₆, THF-d₈ and Et₂O-d₁₀. The characteristic spectral parameters were compared with parent carbodiimides and amidines prepared by hydrolysis, where large solvent effects were described. Five of studied compounds were studied by X-ray diffraction techniques in the solid state. Lithium n-butyl amidinates containing less bulky substituents like isopropyl or cyclohexyl crystallize with Et₂O or THF as centrosymmetric dimers with mutually parallel amidinate moieties. The lithium N,N'-bis[2,6-di(propan-2-yl)phenyl]n-butylamidinate crystallizes from Et₂O solution as an asymmetric dimer. The first unit is composed by one ligand coordinated to one of lithium atoms. The lithium atom is also coordinated by one of the nitrogen atoms of the second ligand. The second nitrogen atom of the same ligand is coordinated to the second lithium atom which is also connected to the Et₂O molecule and the aromatic ring of the ligand in a η³-fashion. The same compound crystallizes from the THF solution as a monomeric bis-tetrahydrofuranate.     

rac‐(Z)‐Ethyl 2‐bromo‐2‐[(3R,5R)‐3‐bromo‐5‐methyl­tetra­hydro­furan‐2‐yl­idene]acetate

In the title compound, C₉H₁₂Br₂O₃, a (tetra­hydro­furan‐2‐yl­idene)acetate, the double bond has the Z form. In the tetra­hydro­furan group, the relative configuration of the Br atom in the 3‐position and the methyl group in the 5‐position is anti. The compound crystallizes with two independent mol­ecules per asymmetric unit and, in the crystal structure, the individual mol­ecules are linked to their symmetry‐equivalent mol­ecules by C—H⋯O hydrogen bonds, so forming centrosymmetric hydrogen‐bonded dimers.     

An efficient synthesis of furyl sulfonamides from the reaction of furan with in situ generated N-tosyl imines

Treatment of an aldehyde and furan with N-sulfinyl-p-toluenesulfonamide/zinc chloride leads to the formation of furyl sulfonamides via an in situ generated N-tosyl imine intermediate. In one case, a novel 4-tosylamino-5,6-dihydro-4H-3-oxa-benz[e]azulene was obtained by intramolecular aromatic substitution of the activated imine at the 3-position of the furan ring.