Nucleophilic (phenylsulfinyl)difluoromethylation of carbonyl compounds with difluoromethyl phenyl sulfoxide

We have successfully achieved nucleophilic (phenylsulfinyl)difluoromethylation of both enolizable and non-enolizable aldehydes and ketones by using difluoromethyl phenyl sulfone (1) as the fluoroalkylating agent. Although the chemical yields of the reactions are good to excellent, the observed diastereoselectivity is poor (dr = 1:1.04-2.03). The present synthetic methodology provides a convenient alternative for the preparation of α-(phenylsulfinyl)difluoromethylated carbinols that were previously synthesized via a two-step procedure.     

Folic acid analogs. III. N-(2-[2-(2,4-diarnino-6-quinazolinyl)ethyl]benzoyl)-l-glutamic acid

A trideaza analog of aminopterin, N-(4[2-(2,4-diamino-6-quinazolinyl)ethyl]benzoyl)-L-glutamic acid, was prepared by a Wittig condensation of 2,4-diaminoquinazoline-6-carboxaldehyde and [P-(N-[1,3-bis(ethoxycarbonyl)propan-1-yl]aminocarbonyl)phenylmethyl]triphenylphosphonium bromide followed by catalytic reduction and mild hydrolysis. This compound was found to have confirmed inhibitory activity against leukemia L1210 in mice.     

2-(Aminomethyl)phthalimide. A new reagent for the synthesis of 2,4-benzodiazepines

2,4-Benzodiazepines can be prepared by condensation of an activated 2-benzoylbenzoic acid with 2-(aminomelhyl)phthalimide. A synthesis of this reagent is described.     

Some approaches to the synthesis of fluorinated alcohols and esters. III. Synthesis of 2-(F-alkyl)ethanols from 2-(F-alkyl)-1-iodoethanes and amides.

1-Iodo-2-(F-alkyl)ethanes, R_FCH₂CH₂I, when heated with a large excess of N-methylformamide (NMF) give in high yield, mixtures of predominately R_FCH₂CH₂OH, some formate ester and a little R_FCHCH₂. In a study of this process, significant variables were examined, including solvent, reactant ratio, effect of water, and alternative amide reactants. The coproduct from NMF is the amidine salt, [MeNHCH(NHMe)]⁺I⁻. By contrast, R_FCH₂CH₂I with N,N-dimethylformamide (DMF) and water (one or two mols) gives chiefly the formate ester; the coproduct is Me₂NH₂⁺I⁻. A mechanistic scheme is proposed: in the first step, an alkyl imidate salt, e.g., [HC(NH Me)OCH₂CH₂R_F]⁺I⁻ is formed by O-alkylation of NMF; reaction of the imidate with more NMF gives a tetrahedral intermediate that breaks down rapidly to R_FCH₂CH₂OH, and HC(NHMe)NMeCHO⁺I⁻. The formate ester is derived from the alcohol and this N-formyl acylating agent, in a subsequent step. Analogously, the alkyl imidate salt from DMF and R_FCH₂CH₂I reacts with water as nucleophile (but not with DMF) to give a tetrahedral intermediate that cleaves under stereoelectronic control to formate ester and amine salt, but not to alcohol. Quantitative isolation of amine salt and amidine salt, and observed rates of reaction give solid support to this proposed mechanism.     

Synthesis and Crystal Structure of N,N'-bis(2-aminoethyl)-2,4-pentanediiminatogold(III) Perchlorate

A synthetic procedure is described for N,N^'-bis(2-aminoethyl)-2,4-pentanediiminatogold(III) perchlorate. The complex was investigated by X-ray phase and X-ray diffraction analyses, electron spectroscopy, and IR spectroscopy. Crystal data for C₉H₁₉AuN₄Cl₂O₈: a = 10.093(2), b = 7.1740(10), c = 22.985(5) , = 90.35(3)°, V = 1664.2(5) ³, space group P2(1)/n, Z = 4, d _calc = 2.324 g/cm³. The structure consists of nearly planar acyclic cations [C₉H₁₉AuN₄]²⁺ and perchlorate anions [ClO₄]^–. The C–C and C–N bonds inside the -diiminate ring are delocalized. The parameters of the [C₉H₁₉AuN₄]²⁺ cation are compared with those in related complexes. The compound is stable in air for at least half a year; solubility in water is 0.8%.     

Reactions of 2-(1-carboxyl-2-hydroxyphenyl)thiazolidine with chromium(III) salts leading to newer synthesis of chromium(III) complexes

Reactions of 2-(L-carboxyl-2-hydroxyphenyl)thiazolidine with different chromium(III) salts [CrCl₃?·?6H₂O, K₃[Cr(SCN)₆], NH₄[Cr(NH₃)₂(SCN)₄]?·?H₂O, [Cr(urea)₆]Cl₃?·?3H₂O and [Cr(CH₃COO)₂H₂O]₂] under varied reaction conditions afforded many new mixed-ligand chromium(III) complexes. The ligand is a tridentate dibasic NSO donor except for complexes 1 and 4 where two moles of the ligand are present for each molecule of complex, one functioning as a dibasic tridentate (NSO) and the other as a monobasic bidentate (NS) (phenolic OH and carboxylic COOH groups remaining uncoordinated). The complexes have been characterized by elemental analyses, magnetic susceptibilities, molar conductances, molecular weights and spectroscopic (IR, Uv-vis) data. The ligand field parameters and NSH Hamiltonian parameters suggest tetragonal geometries of the complexes.     

Convenient and efficient stereoselective synthesis of (2Z)-2-(chloromethyl)alk-2-enoates using iron(III) or indium(III) chloride

The stereoselective synthesis of (2Z)-2-(chloromethyl)alk-2-enoates has been achieved efficiently and in high yields and in short reaction times from Baylis-Hillman adducts, 3-hydroxy-2-methylene-alkanoates, by treatment with FeCl₃ or InCl₃ at room temperature.     

Highly sensitive laser fluorimetry of europium(III) with1,1,1-trifluoro-4-(2-thienyl)-2,4-butanedione

The detection limit for tris(1,1,1-trifluoro-4-(2-thienyl)-2,4-butanediono)-europium(III) is established as 2 pg l^-1. A highly sensitive fluorimetric system consisting of a nitrogen laser and a pulse-gated photon counter is used.     

Synthesis of methoxy-2-quinolones via pummerer-type cyclization of N-aryl-N-methyl-3-(phenylsulfinyl)propionamides

The thionium ions 10 generated by Pummerer reaction of N-aryl-N-methyl-3-(phenylsulfinyl)propionamides 4 caused not only an electrophilic cyclization reaction producing 2-quinolones 8, but also the formation of the vinyl sulfides 5 and 6 in favor of the latter reaction. On the other hand, the treatment of the vinyl sulfides 5 and 6 with p-toluenesulfonic acid induced cyclization to afford the 2-quinolones 8 in excellent to moderate yields, depending on the electronic properties of the aromatic ring, thus providing a convenient method for the synthesis of methoxy-2-quinolones.     

3-(2-Pyrrolidinyl)-2,4-furandione analogs

The reaction of 4,4-dimethyl-3-oxobutanoic (or pentanoic) acid esters with the lactim ether of 2-pyrrolidone in the presence of 2-hydroxypyridine produces condensation products 4 in 57–72% yield. Acidic hydrolysis of 4 affords the furandione system 5 in 75–81% yield.     

Highly efficient, multigram and enantiopure synthesis of (S)-2-(2,4′-bithiazol-2-yl)pyrrolidine

(S)-2-(4-Bromo-2,4′-bithiazole)-1-(tert-butoxycarbonyl)pyrrolidine ((S)-1) was obtained as a single enantiomer and in high yield by means of a two-step modified Hantzsch thiazole synthesis reaction when bromoketone 3 and thioamide (S)-4 were used. Further conversion of (S)-1 into trimethyltin derivative (S)-2 broadens the scope for further cross-coupling reactions.     

Enantioselective synthesis of axially chiral 1-(1-naphthyl)isoquinolines and 2-(1-naphthyl)pyridines through sulfoxide ligand coupling reactions

Racemic 1-(1′-isoquinolinyl)-2-naphthalenemethanol rac-12 was prepared through a ligand coupling reaction of racemic 1-(tert-butylsulfinyl)isoquinoline rac-7 with the 1-naphthyl Grignard reagent 10. Resolution of rac-12 was achieved through chromatographic separation of the Noe-lactol derivatives 14 and 15, providing (R)-(−)-12 of >99% ee and (S)-(+)-12 of 90% ee. The ligand coupling reaction of optically enriched sulfoxide (S)-(−)-7 (62% ee) with Grignard reagent 10 furnished rac-12, with the absence of stereoinduction resulting from competing rapid racemisation of the sulfoxide 7. Reaction of optically enriched (S)-(−)-7 with 2-methoxy-1-naphthylmagnesium bromide was also accompanied by racemisation of the sulfoxide 7, and furnished optically active (+)-1-(2′-methoxy-1′-naphthyl)isoquinoline (+)-3b in low enantiomeric purity (14% ee). The absolute configuration of (+)-3b was assigned as R using circular dichroism spectroscopy, correcting an earlier assignment based on the Bijvoet method, but in the absence of heavy atoms. Optically active 2-pyridyl sulfoxides were found not to undergo racemisation analogous to the 1-isoquinolinyl sulfoxide 7, with the ligand coupling reactions of (R)-(+)- and (S)-(−)-2-[(4′-methylphenyl)sulfinyl]-3-methylpyridines, (R)-(+)-17 and (S)-(−)-17, with 2-methoxy-1-naphthylmagnesium bromide providing (−)- and (+)-2-(2′-methoxy-1′-naphthyl)-3-methylpyridines, (−)-18 and (+)-18, in 53 and 60% ee, respectively. The free energy barriers to internal rotation in 3b and 18 have been determined, and the isoquinoline (R)-(−)-12 examined as a ligand in the enantioselectively catalysed addition of diethylzinc to benzaldehyde; (R)-(−)-12 was also converted to (R)-(−)-N,N-dimethyl-1-(1′-isoquinolinyl)-2-naphthalenemethanamine (R)-(−)-19, and this examined as a ligand in the enantioselective Pd-catalysed allylic substitution of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate.     

Vibrational spectroscopic force field studies of dimethyl sulfoxide and hexakis(dimethyl sulfoxide)scandium(III) iodide, and crystal and solution structure of the hexakis(dimethyl sulfoxide)scandium(III) ion

Hexakis(dimethyl sulfoxide)scandium(III) iodide, [Sc(OS(CH(3))(2))(6)]I(3) contains centrosymmetric hexasolvated scandium(III) ions with an Sc-O bond distance of 2.069(3) angstroms. EXAFS spectra yield a mean Sc-O bond distance of 2.09(1) angstroms for solvated scandium(III) ions in dimethyl sulfoxide solution, consistent with six-coordination. Raman and infrared absorption spectra have been recorded, also of the deuterated compound, and analysed by means of normal coordinate methods, together with spectra of dimethyl sulfoxide. The effects on the vibrational spectra of the weak intermolecular C-H...O interactions and of the dipole-dipole interactions in liquid dimethyl sulfoxide have been evaluated, in particular for the S-O stretching mode. The strong Raman band at 1043.6 cm(-1) and the intense IR absorption at 1062.6 cm(-1) have been assigned as the S-O stretching frequencies of the dominating species in liquid dimethyl sulfoxide, evaluated as centrosymmetric dimers with antiparallel polar S-O groups. The shifts of vibrational frequencies and force constants for coordinated dimethyl sulfoxide ligands in hexasolvated trivalent metal ion complexes are discussed. Hexasolvated scandium(iii) ions are found in dimethyl sulfoxide solution and in [Sc(OSMe(2))(6)]I(3). The iodide ion-dipole attraction shifts the methyl group C-H stretching frequency for (S-)C-H...I(-) more than for the intermolecular (S-)C-H...O interactions in liquid dimethyl sulfoxide.