One-step synthesis of N-alkyl-2-aryl-2-oxoacetamides and N,N-dialkyl-2-aryl-4H-1,3-benzodioxine-2,4-dicarboxamides

Alkyl isocyanides react with 2-hydroxybenzaldehyde or 2-hydroxy-5-nitrobenzaldehyde to afford N-alkyl-2-aryl-2-oxoacetamides and N²,N⁴-dialkyl-2-aryl-4H-1,3-benzodioxine-2,4-dicarboxamides in nearly 1:1 ratios. Treatment of 2,6-dimethylphenyl isocyanide with 2-hydroxy-5-nitrobenzaldehyde affords only the 2-oxoacetamide derivative.     

Synthesis of N,N-dialkylaminobenzonitriles and halo-(N,N-dialkyl)benzamidines by reaction of halobenzonitriles with lithium amides

3- and 4-N,N-Dialkylaminobenzonitriles and 4-chloro-(N,N-dialkyl)benzamidines were isolated by reacting 4-chlorobenzonitrile with hindered lithium amides under thermodynamic (0 °C) and kinetic control conditions (−78 °C), respectively. As previously reported, a benzyne mechanism seems to be confirmed since N,N-dialkylaminobenzonitriles are formed. Only benzamidines were isolated in fair to high yields at both 0 °C and −78 °C with non-hindered lithium amides. Exploitation and mechanistic rationale of the reaction of different halobenzonitriles are also reported.     

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.     

Fluorsilylsubstituierte N,N- und N,O-bis(trimethylsilyl)-hydroxylamine

Fluoro- und aminofluoro-silanes react with the lithium salt of N,O-bis(trimethylsilyl)hydroxylamine under LiF elimination and substitution. Alkyl- and amino-fluorosilanes give O-fluorosilyl-N,N-bis(trimethylsilyl)hydroxylamines, arylfluorosilanes give N-fluorosilyl-N,O-bis(trimethylsilyl)hydroxylamines. By the further reaction of O-difluorosilyl-N,N-bis(trimethylsilyl)hydroxylamine with the lithiated hydroxylamine, O,O′-fluoromethylsilyldi[N,N-bis(trimethylsilyl)hydroxylamine] is formed. On heating N-difluorophenylsilyl-N,O-bis(trimethylsilyl)hydroxylamine di[fluorophenylsilyl(methyl)amino]pentamethylsiloxane is formed by methyl group migration. The NMR and mass spectra of the compounds are reported.     

N-Dmc protected amino acid aglycones: versatile hydrogenolysis stable acceptors for O-glycosylation

N^α-(4,4-Dimethyl-2,6-dioxocyclohexylidenemethylene) (Dmc) protected l-serine, l-threonine and l-homoserine have been prepared as tert-butyl esters in excellent yields. These hydrogenolysis stable acceptors underwent efficient α-O-glycosylation with an l-fucopyranosyl bromide donor and also allowed convenient protecting group manipulations to ultimately deliver novel glycoamino acid building blocks suitable for Fmoc based solid-phase glycopeptide synthesis.     

Reaction of N,N-diarylamidines with 3,4,5,6-tetrachloro-1,2-benzoquinone

A synthesis of 5,11b-dihydro-1H-dibenzo[d,f][1,3]diazepin-1-ones was found in the reaction of nitro-substituted N¹,N²-diarylamidines with 3,4,5,6-tetrachloro-1,2-benzoquinone. In contrast, 6,7,8,9-tetrachlorodibenzodioxins were obtained from reaction of N¹,N²-diphenylpropionamidine and N¹,N²-di-(4-tert-butylphenyl)acetamidine with 3,4,5,6-tetrachloro-1,2-benzoquinone.     

Enantioselective aldol reactions of trichlorosilyl enol ethers catalyzed by chiral N,N-dioxides and monodentate N-oxides

Chiral N,N^′-dioxides and monodentate N-oxides were employed as catalysts in catalytic, enantioselective aldol reactions of trichlorosilyl enol ethers. The reactions of acyclic enol ethers using N,N^′-dioxides resulted in the anti-adducts from (E)-enol ethers and the syn-adducts from (Z)-enol ethers. The reactions of cyclic (E)-enol ethers using N,N^′-dioxides gave the anti-adducts, whereas monodentate N-oxides predominantly gave the syn-adducts.     

Synthesis and characterization of (N→B) phenyl[N-alkyl-N-(2-alkyl)aminodiacetate-O,O′,N]boranes and phenyl[N-alkyl-N-(2-alkyl) aminodiacetate-O,O′,N]boranes

The reaction of boron heterocycles 1 and 2 with n-butyl lithium and alkyl halides led to (N→B) phenyl[N-alky-N-(2-alkyl)aminodiacetate-O,O′,N]boranes 3–6(a–b), 7(b) and 9(b), where alkyl can be in exo and/or endo position, and phenyl[N-alkyl-N-(2-alkyl)aminodiacetate-O,O′,N]boranes 7(c) and 8(c) isomers, which do not display the intramolecular N→B coordination bond. The existence of steric interactions between N-benzyl and the alkyl group at 2 position was indicated by ¹H and ¹³C NMR, while, the δ(¹¹B) values confirm the tetrahedral and trigonal environment of the ¹¹B nucleus in these compounds. Moreover, the compounds were characterized by COSY, HETCOR and homonuclear proton decoupling experiment. The study of the intramolecular N→B coordination by dynamic NMR afforded a ΔG‡ value of 81.09 kJ/mol for compound 6(b).     

Reaction of ferrocenecarboxylic acid with N,N-disubstituted carbodiimides: synthesis, spectroscopic and X-ray crystallographic analysis of N,N-disubstituted N-ferrocenoylureas and identification of a one-pot coupling reagent for the formation of ferrocenecarboxamides in a non-aqueous solvent

N,N^′-dicyclohexyl-N-ferrocenoylurea 2, N,N^′-diisopropyl-N-ferrocenoylurea 3, N,N^′-di-p-tolyl-N-ferrocenoylurea 4 and N,N^′-di-tert-butyl-N-ferrocenoylurea 5 were obtained by reaction of ferrocenecarboxylic acid 1 with N,N^′-dicyclohexylcarbodiimide (DCC), N,N^′-diisopropylcarbodiimide (DIC), N,N^′-di-p-tolylcarbodiimide 10 and N,N^′-di-tert-butylcarbodiimide 11, respectively. Both N-tert-butyl-N^′-ethyl-N-ferrocenoylurea 6 and N^′-tert-butyl-N-ethyl-N-ferrocenoylurea 7 were obtained by reaction of 1 with N-tert-butyl-N^′-ethylcarbodiimide 12. In all cases a small amount of ferrocenecarboxylic anhydride 8 was formed as a by-product. All compounds were characterized by ¹H NMR, ¹³C NMR, IR and MS. Single crystal X-ray structural analyses were made of 2, 3 and 4. From the consistent results, the reaction products of 1 with carbodiimides appear different from those proposed by some earlier workers. With N-(3-dimethylaminopropyl)-N^′-ethylcarbodiimidehydrochloride 9 ferrocenoylurea was not isolated, but the main product was rather 8. The suitability of 8 as acylation reagent was applied by using 9 to obtain N-(3-triethoxysilyl)-propylferrocenecarboxamide in a one-pot reaction from 1 and 3-(triethoxysilyl)-propylamine.     

Polyisobutylene-supported N-heterocyclic carbene palladium catalysts

This paper describes how the nonpolar polymer polyisobutylene (PIB) can be used as a handle to prepare PIB-bound NHC ligands that are soluble in monophasic mixtures of mixed solvents but phase separable when such solvent systems are perturbed to be biphasic. The results here show that such PIB-bound NHC ligands can be used to synthesize useful palladium catalysts. In this paper, both PIB-bound analogs of an N,N′-bis(2,6-diisopropylphenyl) heterocyclic carbene and simpler N,N′-dialkyl heterocyclic carbene ligand were prepared and were successfully used to form palladium cross-coupling catalysts. The reactivity, recycling and reusability of these catalysts has been examined.     

A macromolecular N,N-dichlorosulfonamide as oxidant for residual sulfides

A redox copolymer, a macroporous poly(S/DVB) resin bearing N,N-dichlorosulfonamide groups, was used to remove residual sulfides from aqueous solutions by its oxidation to non-toxic products. The resin contains 8.2 meq active chlorine/g and shows strong oxidizing properties. It was employed in static and flow processes for treatment of sulfide solutions containing 32, 100 or 320 mg S²⁻/dm³. The effects of various parameters on the reaction course have been studied (molar ratio of the reagents, alkalinity of the reaction media, flow rate in column processes). The data showed that the reactive copolymer easily oxidizes sulfides--it was possible to reduce the concentration below 10 μg S²⁻/dm³. During oxidation processes the formation of two end products was confirmed--these were sulfates (in majority) and sulfur which causes the turbidity of the effluents. The reaction conditions to eliminate sulfur formation were sought. To utilize the polymer-bonded active chlorine with good efficiency, it was necessary to maintain a suitable level of alkalinity of the influx. The exhausted copolymer contained unsubstituted sulfonamide groups. It could be regenerated with a slightly acidified sodium chlorate(I) and reused for further processes.     

Stereoselective synthesis of 3-substituted tetrahydroisoquinolines from phthalan and chiral N-sulfinylimines

The reaction of the dianionic intermediate [resulting from the reductive opening of phthalan (1) with lithium] with chiral N-tert-butylsulfinyl aldimines 3 in the presence of ZnMe₂ gives, after hydrolysis, N-tert-butylsulfinyl amino alcohols 4 with high diastereoselectivity. Successive treatment of compounds 4 with hydrogen chloride in methanol, thionyl chloride in chloroform and sodium hydroxide yields 3-substituted tetrahydroisoquinolines 6.     

Synthesis of N-acyl-N,O-acetals from N-aryl amides and acetals in the presence of TMSOTf

Secondary amides undergo in situ silyl imidate formation mediated by TMSOTf and an amine base, followed by addition to acetal acceptors to provide N-acyl-N,O-acetals in good yields. An analogous, high-yielding reaction is observed with 2-mercaptothiazoline as the silyl imidate precursor. Competing reduction of the acetal to the corresponding methyl ether via transfer hydrogenation can be circumvented by the replacement of CY₂NMe with 2,6-lutidine under otherwise identical reaction conditions.     

Efficient guanylation of N,N-difunctionalized polyamines at the secondary amino functions

Treatment of N^α,N^ω-ditritylated linear and aromatic polyamines and of polyamine conjugates of the alkaloid kukoamine A (KukA) type with N,N′-bis(tert-butoxycarbonyl)thiourea in the presence of Mukaiyama’s reagent produced high yields of derivatives guanylated at the secondary amino functions.     

Imino- and bis-imino-pyridines with N-ter-butyl-N-aminoxyl group: synthesis, oxidation and use as ligand towards M ( Mn, Ni, Zn) and Gd

Imino- and bis-iminopyridine ligands bearing N-ter-butylhydroxy groups were synthesized by the condensation reaction between a N-ter-butylhydroxy substituted aniline and 2-formylpyridine, 2-acetylpyridine and 2,6-bis-acetylpyridine. The N-ter-butylaminoxy radicals obtained after oxidation using PbO₂ or Ag₂O were studied by EPR spectroscopy in solution. Indeed, complete decomposition was observed during isolation of these radical derivatives. The N-ter-butylhydroxy substituted ligands obtained were complexed with Mn²⁺, Ni²⁺, Zn²⁺ and Gd³⁺ salts; the obtained complexes were characterized and oxidized to give the aminoxy analogs, which were studied using IR, UV and EPR spectroscopies.     

Multi-step reactions of N-monosubstituted (polyfluoroalkane)thioamides with alkyllithium reagents

Reactions of N-alkyl- or N-aryl(perfluoroalkyl)thiocarboxamides with alkyl lithium reagents are described. Trifluorothioacetamides are converted into the corresponding lithium salts. Compounds bearing a long polyfluorinated chain terminated by a CHF₂ group and compounds containing an N-alkyl substituent with a proton adjacent to nitrogen react further via a multi-step reaction sequence involving HF elimination and then vinylic fluorine substitution and/or S_N′ type fluorine substitution. These transformations led to unsaturated N-monosubstituted polyfluorinated thioamides.     

Application of 13C-n.m.r. spectroscopy to study the mechanism of N-demethylation of [NMe13C] codeine by cell-free extracts of Cunninghamella bainieri

Codeine was synthesized with 90% enrichment of the N-methyl group with carbon-13. N-Demethylation of this substrate by cell-free extracts of Cunninghamella bainieri in an n.m.r, tube gave norcodeine and ¹³C-labelled formaldehyde. Fourier-transform ¹³C-n.m.r. spectroscopy was used to observe the N-demethylation process at selected temperatures. The labelled formaldehyde liberated was trapped with sodium sulphite, and the sulphite adduct, as well as intermediates, were located in the n.m.r, spectrum at each temperature. Intermediate resonances assignable to codeine-N-oxide were not detected during these enzyme-transformation studies. These data suggest that the observed ¹³C-n.m.r. signals correspond to the chemically labile carbinolamine intermediate formed during N-demethylation. A methine ¹³C signal was not observed. Thus, N-demethylation of codeine by Cunninghamella bainieri occurs by direct C-oxidation and not via an N-oxide intermediate.     

Synthesis of pyridine N-imine complexes of methylcobaloxime and reactions of bis(dimethylglyoximato)methyl(Pyridine N-imine)cobalt with acid anyhydrides and acetylenedicarboxylic acid dimethyl ester

Pyridine N-imine complexes of methylcobaloxime, CH₃Co(Hdmg)₂(R¹— C₅H_nN⁺N^?H) (n = 4; R¹ = H, 2-CH₃, 3-CH₃, 4-CH₃: n = 3; R¹ = 2,6-CH₃), have been synthesized by the reaction of CH₃Co(Hdmg)₂S(CH₃)₂ with a pyridine N-imine which is generated from a pyridine, hydroxylamine-O-sulfonic acid and K₂CO₃. The reactions of CH₃Co(Hdmg)₂(C₅H₅N⁺N^?H) with acid anhydrides form new methylcobaloxime complexes with N-substituted pyridine N-imines, CH₃Co(Hdmg)₂(C₅H₅N⁺N^?R²) R² = COPh, COMe, COEt). With maleic anhydride, (pyridine N-acryloylimine)carboxylic acid is formed. With acetylenedicarboxylic acid dimethyl ester, 1,3-dipolar cycloaddition of the ligand gives pyrazolo[1,5-a]pyridine-2,3-dicarboxylic acid dimethyl ester.     

Direct observation of aziridinium ions in a 2-(N,N-dibenzylamino)- to 1-(N,N-dibenzylamino)phosphonate rearrangement

Aziridinium mesylates stable in the reaction medium for several hours to over a week were observed in a rearrangement of dimethyl (1R,2S)-2-(N,N-dibenzylamino)-1-mesyloxyethylphosphonates substituted at C2 with Bn, i-Pr and t-Bu to the respective 1-(N,N-dibenzylamino)-2-mesyloxyethylphosphonates. Rates of formation of these aziridinium mesylates and rates of their reactions with poorly nucleophilic mesylate anion were governed by steric and electronic factors. The conformation of (2S,3S)-1,1-dibenzyl-2-(tert-butyl)-3-(dimethoxyphosphoryl)aziridinium mesylate in solution was established based on ¹H and ¹³C NMR spectroscopic studies including a NOESY experiment.