SYNTHESES AND MASS SPECTRAL REARRANGEMENTS OF UNSATURATED BIS-SULPHIDES AND BIS-SULPHONES

Abstract

The synthesis of (E)- and (Z)-1.2-bis(p-fluorophenylsulphenyl)stilbenes (2a and 2b) and 1,2-bis(p-fluorophenylsulphonyl)stilbenes (3a and 3b) was carried out and their configurations were consistent with their stereospecific synthesis. The isomeric 1,1-bis(p-fluorophenylsulphenyl)- and 1,1-bis(p-fluorophenylsulphonyl)-2,2-bis(phenyl)ethylenes (8 and 9) were also synthesised and configurations were established by degradative oxidation. Mass spectral rearrangements of all these compounds were examined. Mass spectra of 1,1-bis-sulphide and 1,1-bis-sulphone bears close relationship with those of (E)- and (Z)-isomeric counterparts. Smiles-type rearrangement observed in 1,2-bis-sulphides was absent in 1,2-bis-sulphones. McLafferty-type rearrangement involving hydrogen migration, from aryl group was noticed in both bis-sulphides and bis-sulphones. Vinyl migration to the sulphone oxygen predominates over aryl migration in three isomeric bis-sulphones.     

Preparation of the enantiopure 1,2-diamine monomer and its polymerization: The efficient polymeric chiral ligand of an asymmetric hydrogenation catalyst

An enantiopure 1,2-diamine monomer possessing a p-vinylbenzyl group as a polymerizable group was synthesized from chiral 1,2-bis(p-hydroxyphenyl)-N,N′-bis(tert-butoxycarbonyl)-1,2-diaminoethane. The chiral monomer was copolymerized with styrene, and this was followed by the deprotection of the tert-butoxycarbonyl group, which yielded the polymer-supported chiral 1,2-diamine. The polymeric catalyst system was established with the polymeric chiral 1,2-diamine complexed with 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl/RuCl₂. In the presence of potassium tert-butoxide (t-BuOK), the polymeric catalyst system worked well in the asymmetric hydrogenation of aromatic ketones. The corresponding chiral secondary alcohols were obtained in quantitative yields with a high level of enantioselectivity. The insolubility of the catalyst, caused by the crosslinked structure of the polymer, made it recyclable. The polymeric catalyst was reused several times without a loss of catalytic activity. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4556–4562, 2004     

Selective,Transition Metal-free 1,2-Diboration of Alkyl Halides,Tosylates, and Alcohols

Defunctionalization of readily available feedstocks to provide alkenes for the synthesis of multifunctional molecules represents an extremely useful process in organic synthesis. Herein, we describe a transition metal-free, simple and efficient strategy to access alkyl 1,2-bis(boronate esters) via regio- and diastereoselective diboration of secondary and tertiary alkyl halides (Br, Cl, I), tosylates, and alcohols. Control experiments demonstrated that the key to this high reactivity and selectivity is the addition of a combination of potassium iodide and N,N-dimethylacetamide (DMA). The practicality and industrial potential of this transformation are demonstrated by its operational simplicity, wide functional group tolerance, and the late-stage modification of complex molecules. From a drug discovery perspective, this synthetic method offers control of the position of diversification and diastereoselectivity in complex ring scaffolds, which would be especially useful in a lead optimization program.     

A tandem of the Cornforth rearrangements of 4-(1,2,3-triazol-1-yl)iminomethyl-1,2,3-thiadiazole

The method for the synthesis of 5-(2,6-dimethylmorpholino)-1,2,3-thiadiazole-4-carbaldehyde was proposed. Its reaction with sodium 1-amino-4-(N-methyl)carbamoyl-1,2,3-triazol-5-olate proceeds through a tandem of the Cornforth rearrangements. The initially formed azomethine isomerizes into sodium 4"-(2,6-dimethylmorpholino)thiocarbonyl-4-(N-methyl)carbamoyl-1,1"-bis[1,2,3]triazolyl-5-olate, which then rearranges to give sodium 4-{N-[4-(2,6-dimethylmorpholinothiocarbonyl)-1,2,3-triazol-1-yl]carbamoyl}-1-methyl-1,2,3-triazol-5-olate.     

Synthesis of 1,2-bis(methoxyamino)cycloalkanes from alicyclic 1,2-bis(hydroxyamines)

Derivatives of 1,4-dihydroxypiperazine-2,3-dione were obtained by reaction of cis-1,2-bis(hydroxyamino)cycloalkanes with diethyl oxalate. Their alkylation with CH₂N₂ or Mel afforded 1,4-dimethoxypiperazine-2,3-diones. Hydrolysis of the latter gave 1,2-bis(methoxyamino)cycloalkanes.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 925–929, April, 1996.     

Synthesis, structure, and electrochemical properties of biferrocenes annulated with 1,2-dithiin and 1,2-dithiin 1,1-dioxides

2,2″-Bis(N,N-dimethylaminosulfonyl)-1,1″-biferrocene (6), a precursor of biferrocenes annulated with 1,2-dithiin and 1,2-dithiin 1,1-dioxides, was prepared by a sequence of selective ortho-lithiation and dimerization reaction from N,N-dimethylaminosulfonylferrocene. New biferrocenes annulated with 1,2-dithiin (1) and 1,2-dithiin 1,1-dioxides (2) and (3) were successfully synthesized in satisfactory yields by the reaction of compound 6 with lithium aluminum hydride followed by treatment with chlorotrimethylsilane. The electrochemical properties of the biferrocenes (1)-(3) were furnished by voltammetric studies.     

Allgemeiner Zugang zu Polyaminen mit Ethan-1,2-diamin-Einheiten: Synthese von nicht natürlich vorkommenden homologen und isomeren N1,4-Di(4-cumaroyl)sperminen

█tl="American"█The synthesis of the three N,N′-di(4-coumaroyl)tetramines, i.e., of (E,E)-N-{3-[(2-aminoethyl)amino]propyl}-3,3′-bis(4-hydroxyphenyl)-N,N′-(ethane-1,2-diyl)bis[prop-2-enamide] ( 1a ), (E,E)-N-{4-[(2-aminoethyl)amino]butyl}-3,3′-bis(4-hydroxyphenyl)-N,N′-(ethane-1,2-diyl)bis[prop-2-enamide] ( 1b ), and (E,E)-N-{6-[(2-aminoethyl)amino]hexyl}-3,3′-bis(4-hydroxyphenyl)-N,N′-(ethane-1,2-diyl)bis[prop-2-enamide] ( 1c ), is described. It proceeds through stepwise construction of the symmetric polyamine backbone including protection and deprotection steps of the amino functions. Their behavior on TLC in comparison with that of 1,4-di(4-coumaroyl)spermine (=(E,E)-N-{4-[(3-aminopropyl)amino]butyl}-3,3′-bis(4-hydroxyphenyl)-N,N′-(propane-1,3-diyl)bis[prop-2-enamide]; 2 ) is discussed.     

Reaction of esters,ortho esters,acetals, thioacetals and epoxides with 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide (Lawesson reagent)

2,4-Bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide,LR, reacted with ethyl formate, triethoxymethane, 1,1,1-triethoxyethane and tetraethoxymethane to give2a and3. 1,1-diethoxymethylbenzene when treated withLR produced2a,3,7,8, and9b. Triethoxymethylbenzene when heated withLR gave2a,8 and11. The reaction of benzyl formate, tris(benzyloxy)methane and 1,1-dibenzyloxy-N,N-dimethylmethanamine withLR afforded2b. Bis(methylthio)methane, tris(ethylthio)methane and 1,1-bis(butylthio)ethane withLR gave9. 1,1-Bis(2,2-dimethylpropoxy)-N,N-dimethylmethanamine withLR yielded2c and17. The reaction of 1,2-epoxyethylbenzene withLR gave20, while 1,2-epoxypropane or 1,2-epoxybutane withLR afforded23 a,b.

---

Reaktionen von Estern, Orthoestern, Acetalen, Thioacetalen und Epoxiden mit 2,4-Bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetan-2,4-disulfid (Lawesson Reagens)

Zusammenfassung Lawesson-Reagens (LR) reagiert mit einer Vielzahl von Verbindungen zu entsprechenden Derivaten. Es wurden folgende Reaktionspartner fürLR eingesetzt: Ethylformiat, Triethoxymethan, 1,1,1-Triethoxyethan, Tetraethoxymethan, 1,1-Diethoxymethylbenzol, Triethoxymethylbenzol, Benzylformiat, Tris(benzyloxy)methan, 1,1-Dibenzyloxy-N,N-dimethylmethanamin, Bis(methylthio)methan, Tris(ethylthio)methan, 1,1-Bis(butylthio)ethan, 1,1-Bis(2,2-dimethylpropoxy)-N,N-dimethylmethanamin, 1,2-epoxyethylbenzol, 1,2-epoxypropan und 1,2-Epoxybutan. Die entstandenen Produkte wurden mittels MS und¹³C- bzw.¹H-Spektroskopie charakterisiert.

     

1,2-Bis(methylamino)ethane-1,2-diol dihydrochloride as a new precursor of 1,2,1",2"-tetramethyl-3,3"-bidiaziridine

Using the synthesis of 1,2-bis(methylamino)ethane-1,2-diol dihydrochloride (5) as an example, it was demonstrated that aliphatic -aminocarbinols can be stabilized as hydrochlorides. The reaction of compound 5 with N-chloromethylamine in CHCl₃ in the presence of K₂CO₃ afforded 1,2,1",2"-tetramethyl-3,3"-bidiaziridine as a mixture of diastereomers (a racemate and a meso form). The meso form was isolated in the individual state and its structure was established by X-ray diffraction analysis. The kinetics of inversional epimerization was studied.     

Herstellung von Argininpeptiden mitN 7,N 8-(1,2-Dihydroxycyclohex-1,2-ylen)-Schutz

A method for the synthesis of arginine peptides is described, in which the side chain guanidine function is blocked through reaction with 1,2-cyclohexanedione in borate buffers.Coupling to the carboxyl group of arginine was achieved by active ester, by dicyclohexylcarbodiimide/1-hydroxybenzotriazole¹, and by the mixed anhydride methods². Neither lactam formation nor acylation of the vicinal hydroxyls of the N⁷, N⁸-(1,2-dihydroxycyclohex-1,2-ylene) guanidino group was observed.Removal of the protecting group is strongly influenced by steric factors. Some side reactions observed during modification of peptides and protein fragments with 1,2-cyclohexanedione are also described.

Herrn Professor Dr.Hermann Stetter zum 65. Geburtstag gewidmet.     

A Convenient Synthesis of 2-Arylnaphtho[1,2-d]oxazole Derivatives Promoted by Triethylamine

A variety of 2-arylnaphtho[ 1,2-d]oxazole derivatives were efficiently synthesized in moderate to high yields by the reaction of aromatic aldehydes with 1-amino-2-naphthol derivatives in the presence of triethylamine in refluxing ethanol in air. Seven new 2-arylnaphtho[1,2-d]oxazole derivatives were obtained and characterized by the spectral data and elemental analysis. In addition, the X-ray crystal structures of 2-[4-（N,N-dimethylamino）phenyl]naphtho[ 1,2-d] oxzole （3d） and 1, 1＇-bis（naphtho[ 1,2-d]oxazol-2-yl）ferrocene （3n） have been determined.     

Strain-release 2-azaallyl anion addition/borylation of [1.1.1]propellane: synthesis and functionalization of benzylamine bicyclo[1.1.1]pentyl boronates

We report a 3-component reaction between N-benzyl ketimines, [1.1.1]propellane, and pinacol boronates to generate benzylamine bicyclo[1.1.1]pentane (BCP) pinacol boronates. These structures are analogous to highly sought diarylmethanamine cores, which are common motifs in bioactive molecules. We demonstrate the versatility of the boronate ester handle via downstream functionalization through a variety of reactions, including a challenging Pd-catalyzed (hetero)arylation that exhibits a broad substrate scope. Together, these methods enable the synthesis of high-value BCP benzylamines which are inaccessible by existing methods. Furthermore, we demonstrate the successful application of these newly developed (hetero)arylation conditions to a variety of challenging tertiary pinacol boronates, including nitrogen-containing heterocycles, 1,1-disubstituted cyclopropanes, and other BCP cores.

We report a 3-component reaction between N-benzyl ketimines, [1.1.1]propellane, and pinacol boronates to generate benzylamine bicyclo[1.1.1]pentane (BCP) pinacol boronates.     

Synthesis of Aminoboronic Acid Derivatives from Amines and Amphoteric Boryl Carbonyl Compounds

Herein, we demonstrate the use of α‐boryl aldehydes and acyl boronates in the synthesis of aminoboronic acid derivatives. This work highlights the untapped potential of boron‐substituted iminium ions and offers insights into the behavior of N‐methyliminodiacetyl (MIDA) boronates during condensation and tautomerization processes. The preparative value of this contribution lies in the demonstration that various amines, including linear and cyclic peptides, can be readily conjugated with boron‐containing fragments. A mild deprotection of amino MIDA‐boronates enables access to α‐ and β‐aminoboronic acids in high chemical yields. This simple process should be applicable to the synthesis of a wide range of bioactive molecules as well as precursors for cross‐coupling reactions.     

Stereoselective Synthesis and Diels-Alder Reactions of (Z)- and (E)-1,2-bis(Phenylthio)-1,3-Butadiene

Bromination of 3-phenylthio-2-sulfolene (2) with N-bromosuccinimide gave 2-bromo-3-phenylthio-2-sulfolene (3) which was converted mainly to 2,3-bis(phenylthio)-2-sulfolene (4) by treatment with sodium phenylthiolate. Thermal desulfonylation of 4 at different temperatures in the presence of a base (DBU) yielded stereoselectively the (Z)- and (E)-1,2-bis(phenylthio)-1,3-butadiene (6). These two geometric isomers could be thermally interconverted. The Diels-Alder reactions of 6 were also investigated. Only the (Z)-diene 6a could undergo the Diels-Alder reaction; the (E)-diene 6b was in situ converted to the Z isomer before undergoing (he Diels-Alder reaction. The reaction of 6a with N-phenylmaleimide gave the cycloaddition product 7 with complete endo selectivity, but under daylight or during chromatography it readily underwent a thioallylic rearrangement to yield 8 with inversion of configuration. The cycloaddition of 6a with methyl acrylate proceeded regiospecifically, but generating a mixture of endo and exo isomers. The endo/exo ratio could be increased by using ZnCl₂ as the catalyst.     

Programmable Amine Synthesis via Iterative Boron Homologation

The value of Matteson-type reactions has been increasingly recognized for developing automated organic synthesis. However, the typical Matteson reactions almost exclusively focus on homologation of carbon units. Here, we report the detailed development of sequential insertion of nitrogen and carbon atoms into boronate C−B bonds, which provides a modular and iterative approach to access functionalized tertiary amines. A new class of nitrenoid reagents is uncovered to allow direct formation of aminoboranes from aryl or alkyl boronates via N-insertion. The one-pot N-insertion followed by controlled mono- or double-carbenoid insertion has been realized with widely available aryl boronates. The resulting aminoalkyl boronate products can undergo further homologation and various other transformations. Preliminary success on homologation of N,N-dialkylaminoboranes and sequential N- and C-insertions with alkyl boronates have also been achieved. To broaden the synthetic utility, selective removal of a benzyl or aryl substituent permits access to secondary or primary amine products. The application of this method has been demonstrated in the modular synthesis of bioactive compounds and the programmable construction of diamines and aminoethers. A plausible reaction mechanism, supported by preliminary NMR (nuclear magnetic resonance) and computational studies, is also proposed.     

N-Cyanomethyl-β-chloroamines: a convenient source of aziridinium ions

N-Cyanomethyl-β-chloroamines smoothly react with a range of alcohols or amines to give regio- and stereoselectively 1,2-aminoethers or 1,2-diamines. The reaction proceeds through the formation of an intermediate aziridinium ion. The N-cyanomethyl group can then be cleaved easily.     

Eine neue Synthese von Tetrachlordiphosphan sowie Untersuchungen zur 1,2-Addition an Cycloalkene

A New Synthesis of Tetrachlorodiphosphane and Investigations Concerning the 1,2-Addition to Cycloalkenes . The phosphorus subhalide P₂Cl₄ has been synthesized by co-condensation of PCl₃ and Cu vapour in 14% yield. The ³¹P-NMR chemical shift of P₂Cl₄ has the value of δ=155. P₂Cl₄ decomposes during several hours at 0°C in a N₂ atmosphere by a disproportionation process to yield PCl₃ and a yellow polymeric compound of the approximately composition (PCl)_x. P₂Cl₄ is flammable in air to give POCl₃ and (PCl)_x. Investigations regarding the addition of P₂Cl₄ to cyclooctyne, cyclohexene, and cyclohexa-1,4-diene has been carried out. Surprisingly, cyclooctyne does not react with P₂Cl₄ but cyclohexene as well as cyclohexa-1,4-diene undergo 1,2-addition to yield the trans-1,2-bis(dichlorophosphino) substituted carbonhydrides. By derivatization with Me₃Si—NMe₂ the corresponding trans-1,2-bis[bis(dimethylamino)phosphino] compounds are synthesized.     

Cyclothiomethylation of aliphatic polyamines with formaldehyde and hydrogen sulfide

Cyclothiomethylation of the terminal amino groups in N-(2-aminoethyl)ethane-1,2-diamine, N,N′-bis(2-aminoethyl)ethane-1,2-diamine, and N,N′-bis(2-aminoethyl)ethane-1,1-diamine with formaldehyde and hydrogen sulfide gave the corresponding bis-1,3,5-dithiazinane derivatives. The reaction in aqueous butanol at 0°C was accompanied by intermolecular thiomethylation at the secondary amino groups with formation of previously unknown polyheterocyclic compounds containing nitrogen and sulfur atoms.     

Reactions of indoles with ortho esters,N,N-dimethylformamide and N,N-dimethylacetamide dialkyl acetals

Indole and N-methylindole react with oxa stabilized carbocations generated in situ from orthoformates to yield tris(3-indolyl)methane. The unsymmetrical isomers, e.g. 2-(N-methyl-3-indolyl)di(N-methyl-3-indolyl)-methane ( 4 ), were not formed as established by an independent synthesis. N,N-Dimethylacetamide dimethyl-acetal reacted with 2-alkyl substituted indoles to produce 1,1-bis(3-indolyl)ethanes ( 3 ).     

Use of effective fragment potentials for simulation of excited states in an inhomogeneous environment

Singlet and triplet spectra of phosphorescent organic light-emitting diode dopants such as bis(2-methyldibenzo[f,h]quinoxaline)(acetylacetonate)iridium(III) in inhomogeneous amorphous hosts are simulated by time-dependent density functional theory (TDDFT) using molecular dynamics and effective fragment potentials (EFPs). The EFPs of the host molecules N,N′-di(1-naphthyl)-N,N′-diphenyl-(1,1′-biphenyl)-4,4′-diamine and 4,4′-bis(N-carbazolyl)-1,1′-biphenyl are constructed from small fragments. The procedure for breaking large molecules into fragments and constructing an EFP is presented. It is demonstrated that polarizable inhomogeneous environment affects the position, intensity, and width of the spectral bands and, therefore, should be taken into account in accurate simulations of spectral bands.