Head-to-head polymers. XV. A facile synthesis of 2,3-disubstituted succinates and butanediols-1,4

A synthetic approach that makes symmetrically 2,3-dialkyl-substituted succinates and compounds prepared from 2,3-dialkyl-substituted succinates easily available has been developed. Coupling of α-bromoalkanoic esters with a zinc/copper couple produced in about 40% yield 2,3-disubstituted succinates which were reduced with LiAlH₄ to 2,3-disubstituted butanediols-1,4 in nearly quantitative yields. Some 2,3-disubstituted butanediols-1,4 were cyclodehydrated under reduced pressure with KHSO₄ to 3,4-disubstituted tetrahydrofurans or acetylated and the diacetyl compounds pyrolyzed at 525°C to 2,3 disubstituted butadienes-1,3. The length of the alkyl chains of the 2,3-dialkylsuccinates and consequently the 2,3-dialkylbutanediols-1,4 ranged from C₂ to C₁₆. 2,3-Disubstituted butanediols-1,4, 2,3-disubstituted butadienes-1,3, and 3,4-disubstituted tetrahydrofurans are interesting monomers for polymerization experiments.     

Réactivité de l'hypochlorite de tertiobutyle dans l'oxydation du benzothiophene

In reaction with benzothiophene, t-butyl hypochlorite acts as an oxidizing reagent and a chlorination reagent. A mixture of 3-ehlorobenzothiophene, three 2,3-dichloro-2,3-dihydrobenzothio-phene 1-oxide isomers (trans-anti: trans-syn; cis-anti) and 2-chlorobenzothiophene 1-oxide was obtained. With a large exces of t-butyl hypochlorite, the reaction leads to 2,3-dichlorobenzothio-phene, 2,3-dichlorobenzothiophene 1-oxide. 2,2,3-trichloro-2,3-(lihydrobenzothiophene 1-oxide and 2,3-dichloro-3-oxobenzothio-phene 1-oxide. In any case, oxidation stops at the level of the sulfoxide.     

DFT and experimental investigation of catecholate derivatives of benzoic acid and pyridine

DFT calculations, at the B3LYP/TZVP level of theory for pyrocatechuic acid (2,3-dihydroxybenzoic acid, 2,3-DHBA), 2,3-dihydroxy-pyridine 2,3-DHPY and their ionized and oxidized forms, have been performed, in combination with experimental data. ¹H, ¹³C, 2D COSY NMR, IR and electronic spectra were coupled to the theoretical calculations. The geometrical parameters were checked by reported crystallographic data. The neutral form of pyrocatechuic acid is the most stable, regarding its ionized (mono-, di- or tri-anions) and oxidized ([2,3-DHBA-sqH]⁻, [2,3-DHBA-sq]²⁻, [2,3-DHBA-q]⁻) species. The most stable conformer 2,3-DHBA-H₃ displays the COOH– group co-planar to the catechol ring, hydrogen bonded with OH(2). In the [2,3-DHBA-H₂]⁻ the stable conformer shows the presence of protonated COOH, while OH(2) is ionized. The tri-anion is the form of 2,3-DHBA with the highest energy. Among the protonated semiquinone radical forms [2,3-DHBA-sqH]⁻, more stable is the OH(3)-oxidized, cited 21.3 kcal/mol lower in energy from the OH(2)-oxidized; in this latter the COO⁻ group lies perpendicular to the benzene ring. The same calculation procedure fitted on the oxygenated [2,3-DHBA-H-O₂]²⁻ shows a weak π-bonding between O(2) and dioxygen, strongly H–bonded to OH(3), while the C(2)–O bond order increases. The different way of 2,3-DHBA oxidation parallels the different, from 3,4-isomer, degradation products. Our DFT calculations show that the keto/enol tautomeric forms of the neutral 2,3-DHPY-H₂ differ by 5.02 kcal/mol. Both species give, upon ionization, the [2,3-DHPY-H]⁻ with the OH(2) deprotonated. The electronic density distribution of [2,3-DHPY-q] justifies further reactions (degradation or dienic addition) as experimentally observed.     

Reduction of 2,3-<Emphasis Type="Italic">Seco</Emphasis>-28-oxo-19<Emphasis Type="Italic">β</Emphasis>,28-epoxy-18<Emphasis Type="Italic">α</Emphasis>-olean-2,3-dicarboxylic acid and its cyclic anhydride

Reduced derivatives of 2,3-seco-28-oxo-19β,28-epoxy-18α-olean-2,3-dicarboxylic acid and its cyclic anhydride were prepared. Reduction of the starting 2,3-secodicarboxylic acid by NaBH₄–I₂ produced the 2,3-seco-2,3-dihydroxy derivative. Reaction of the starting anhydride with LiAlH₄ gave the 2,3-seco2,3,19β,28-tetrahydroxy derivative. Cyclization using acidic reagents of the 2,3-seco-2,3-hydroxy- and 2,3seco-2,3,19β,28-tetrahydroxy derivatives gave the corresponding cyclic ethers containing an oxepane ring. The anhydride ring was reduced by NaBH₄ to the corresponding ε-lactone, the structure of which was confirmed by an x-ray crystal structure.     

syn-2,3-Disubstituted-2,3-dihydro-1,4-benzoxathiin rings: preparation from quinone ketals and 2-mercaptoethanols

A general method for the preparation of syn-2,3-disubstituted-2,3-dihydro-1,4-benzoxathiin rings from 2-mercaptoethanols and quinone ketals is presented. This ring system is produced by Michael addition of a 2-mercaptoethanol to a quinone ketal, followed by cyclization of the initial Michael adduct, and subsequent aromatization to afford a syn-2,3-disubstituted-1,4-benzoxathiin in fair to good chemical yield. Several chiral syn-2,3-disubstituted-2,3-dihydro-1,4-benzoxathiin rings were prepared with this method from enantioenriched 2-mercaptoethanols. No loss of enantiopurity was observed.     

X-ray crystallographic and NMR structural studies of trans-2,3-dichloro-5-ethyl-2,3-dihydrothieno[2 3-b]pyridine syn-1-oxide reactions of thiophene rings with hypochlorite reagents

X-ray analysis of a crystalline product obtained by treatment of 5-ethylthieno[2,3-b]pyridine with excess acidified hypochlorite establishes its stereochemistry as trans-2,3-dichloro-5-ethyl-2,3-dihydrothieno-[2,3-b]pyridine syn-1-oxide (5), wherein the pyridine ring is planar and the dihydrothiophene ring is non-planar with a C2-S-C7a angle of 86.6°. The trans geometry is corroborated by a proton-proton coupling constant J_2,3 of 6.8 Hz. Comparison of ¹H and ¹³C nmr data for 5 with analogous crystalline 2,3-dichloro-1-oxide addenda isolated in the isosteric benzo[b]thiophene and thieno[2,3-b]pyridine parent systems indicates that some proposed stereochemical assignments are questionable.     

Synthesis of vicinal bishydroxylamine

Reduction of 2,3-dimethyl-2,3-dinitrobutane with Zn in aqueous ethanol in the presence of NH₄Cl affords 2,3-bis(hydroxylamino)-2,3-dimethylbutane together with 2,3-diamino-2,3-dimethylbutane and complex Zn salts. A modified procedure was developed for the synthesis of bishydroxylamine, which involves reduction in a Zn/NH₄Cl/THF−H₂O system. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1539–1545, August, 1999.     

Head-to-head polymers — XXXII: Toward head-to-head poly(α-methylstyrene): Synthesis of 2,3-dimethyl-2,3-diphenylbutanediol-1,4-ditosylate and 1,4-diphenyl-2,3-dimethylbutadiene-1,3

2,3-Dimethyl-2,3-diphenylbutanediol-1,4-ditosylate (7) was synthesized starting from 2-phenylpropionic acid (1). The acid chloride was brominated and transformed into methyl 2-phenyl-2-bromo-propionate (4) which was coupled with a zinc/copper couple to dimethyl 2,3-dimethyl-2,3-diphenylsuccinate (5). Reduction with lithium aluminum hydride to 2,3-dimethyl-2,3-diphenylbutanediol-1,4 (6) was followed by tosylation. The tosylate 7 a mixture of the meso and racemic compounds, could be separated into the pure isomers,a m. p. 170 °C andb m. p. 121 °C. The mixture of each individual pure compound, when treated with tetraalkyl-ammonium bromide, did not give the expected 2,3-dimethyl-2,3-diphenyl-1,4-dibromobutane (9) but rather 1,4-diphenyl-2,3-dimethylbutadiene-1,3 (8). The identity of the compound was established by independent unequivocal synthesis, the comparison of spectral characteristics, and mixed melting point.     

Reactions of 2,3-diferrocenylcyclopropenone with methyllithium and phenyllithium

Reactions of 2,3-diferrocenylcyclopropenone with methyllithium and phenyllithium afford products of the nucleophilic opening of the three-membered ring, viz., α,β-unsaturated ketones (cis-3,4-diferrocenylbut-3-en-2-one and cis-2,3-diferrocenyl-1-phenylprop-2-enone) and allylic alcohols (cis-3,4-diferrocenyl-2-methylbut-3-en-2-ol and cis-1,1-diphenyl-2,3-diferrocenylprop-2-en-1-ol). The insertion product of a methyl(diferrocenyl)vinylcarbenoid into a σ-bond of the starting compound, viz., 2,3,4-triferrocenyl-4-(1-ferrocenyl-2-oxopropyl)cyclobutenone, along with intramolecular ortho-alkylation products, viz., 2,3-diferrocenylindanone and 2,3-diferrocenyl-2-hydroxyindanone, were also isolated. X-ray diffraction data for triferrocenylcyclobutenone and 2,3-diferrocenyl-2-hydroxyindanone are presented.     

Five-Membered 2,3-Dioxo Heterocycles: XLVII. Reaction of 5-Aryl-4-phenyl-2,3-dihydrofuran-2,3-diones with Compounds Containing C = N and C≡N Bonds

Thermal decarbonylation of 5-aryl-4-phenyl-2,3-dihydrofuran-2,3-diones gives rise to intermediate aroyl(phenyl)ketenes which react with nonactivated Schiff bases, N,N'-dicyclohexylcarbodiimide, and p-di-methylaminobenzonitrile according to the [4 + 2]-cycloaddition pattern with formation of 6-aryl-5-phenyl-4H-1,3-oxazin-4-ones. Reactions of 5-aryl-4-phenyl-2,3-dihydrofuran-2,3-diones with activated Schiff bases at a temperature below the thermolysis temperature lead to 4-aroyl-4-phenyltetrahydropyrrole-2,3-diones.     

Reaction of 2-bromomethyl-1,3-thiaselenole with thiourea: en route to the first representatives of 2-(organylsulfanyl)-2,3-dihydro-1,4-thiaselenines

The regioselective reaction of 2-bromomethyl-1,3-thiaselenole 1 with thiourea is accompanied by rearrangement, expanding the ring to afford the corresponding six-membered isothiuronium salt, 2-[amino(imino)methyl]sulfanyl-2,3-dihydro-1,4-thiaselenine hydrobromide 2, a synthon of the 2,3-dihydro-1,4-thiaselenin-2-ylthiolate anion. The latter was used for the synthesis of the first representatives of 2-(organylsulfanyl)-2,3-dihydro-1,4-thiaselenines 3a–g, bis(2,3-dihydro-1,4-thiaselenin-2-yl) disulfide 5 and 1,6-bis(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)hexane 6.     

Acetylenchemie, 33. Mitt.: Synthese von 2-substituierten Dihydrofuro[2,3-b]chinolinen

Summary The reaction of 3-iodo-4-methoxy-2(1H)-quinolinone (1) and 3-iodo-4,6,8-trimethoxy-2(1H)-quinolinone (2) with 2-methyl-3-butyn-2-ol under modified Heck-conditions gave the 2-substituted derivatives 2-(1-hydroxy-1-methylethyl)-4-methoxyfuro[2,3-b]-quinoline (3) and 2-(1-hydroxy-1-methylethyl-4,6,8-trimethoxyfuro[2,3-b]-quinoline (4). By a subsequent hydrogenation-reaction with a homogeneous catalyst (PtO₂/Rh₂O₃), the furoquinoline-derivatives yielded the dihydrofuro-[2,3-b]quinolines, identified as 2-(1-hydroxy-1-methylethyl-4-methoxy-2,3-dihydrofuro[2,3-b]quinoline (5) (racemic platydesmine) and 2-(1-hydroxy-1-methylethyl)-4,6,8-trimethoxy-2,3-dihydrofuro-[2,3-b]quinoline (6) (racemic precursor of O⁴-methylptelefolonium salt).

     

Synthesis of novel 5H, 11H‐pyrido[2′,3′:2,3]thiopyrano[4,3‐b]‐indoles by fischer‐indole cyclization

The synthesis of the title compounds 5H, 11H‐pyrido[2′,3′:2,3]thiopyrano[4,3‐b]indoles was accomplished by the Fischer indole cyclization of some 2,3‐dihydrothiopyrano[2,3‐b]pyridin‐4(4H)‐one phenylhydrazones and 7‐methyl‐2,3‐dihydrothiopyrano[2,3‐b]pyridin‐4(4H)‐one phenylhydrazones. The synthesis of the new 2,3‐dihydrothiopyrano[2,3‐b]pyridin‐4(4H)‐one, which was used as one of the starting compounds, is also described.     

Azaindolines: derisking the indoline structural alert

4-Substitued azaindolines, which are isosteres of indolines, are useful synthetic building blocks that reduce the risk of bioactivation induced idiosyncratic toxicity have been prepared. Multigram routes to 2,3-dihydro-1H-pyrrolo[2,3-c]pyridine-4-triflate 16, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile 20 and 4-chloro-2,3-dihydro-1H-pyrrolo[2,3-d]pyridazine 30 are outlined.     

Chemistry of thienopyridines. XIX. Further studies on chlorination and S-oxidation in the thieno[2,3-b] pyridine system

Treatment of thieno [2,3-b] pyridine (1a) with chlorine gas in chloroform (plus water) gave a mixture of two 2,3-dichloro-2,3-dihydrothieno[2,3-b] pyridine 1-oxides [trans-syn (IIa), and cis-anti (IIb)) [and 2,3,3-trichloro-2,3-dihydrothieno[2,3-b]pyridine syn-1-oxide (IVa), as well as a non-isolated fourth product (prohably the anti isomer of IVa) and sometimes a small amount of thieno[2,3-b]pyridine 1,1-dioxide (III). Treatment of Ia in a solvent (water, chloroform-water, or THF-water) with sulfuric acid and sodium hypochlorite gave a mixture of IIb and III. Effects of variations of reaction conditions on the composition of the product mixture were ascertained through chemical isolation and/or pmr analysis. Products formed were rationalized in terms of the chlorine-water-hypochlorous acid equilibrium, plus attack of chlorine variously at positions 1 (S-atom), 2, and 3 of 1a, but of hypochlorous acid only at position 1. Thermal and chromatographic limitations on isolation procedures for some of the products were established. Stereochemistries of IIa, IIb, and IVa were assigned by means of pmr spectrometry with the aid of the shift reagent Eu(fod)₃. Spin-spin couplings between the proton at position 2 and those at positions 4 and 6 were observed at high resolution. In exploratory runs, 5-ethyl-la was converted into isolable 2,3-dichloro-5-ethyl-2,3-dihydrothieno[2,3-b]pyridine 1-oxide, and 5-acetyl-Ia yielded 3-chloro-5-acetylthieno] 2,3-b]pyridine. Mass spectral fragmentation patterns for the various products are presented.     

Azimine. VI. 1-Alkoxycarbony 1-2,3-dialkyl- und -2,3-diaryl-azimine

Azimines VI: 1-Alkoxycarbonyl-2,3-dialkyl- and -2,3-diarylazimines Alkoxycarbonyl-nitrenes 2 – generated in situ by α-elimination from N-[(4-nitrophenyl)-sulfonyloxy]carbamates 4 – were reacted with six aliphatic and aromatic azo compounds to yield 1-alkoxycarbonyl-azimines 11 (R′ = Alkyl). Thus, (2Z)- or (2E)- 1 -alkoxycarbonyl-2,3-diisopropyl-azimines ( 8 or 9 ) were obtained stereospecifically from (E)- or (Z)-1,1′-dimethylazoethane ( 5 or 6 ) and 1-alkoxycarbonyl -2,3-(cis-1,3-cyclopentylene)-azimines ( 10 ) resulted from 2,3-diazabicyclo[2.2.1]-2-heptene ( 7 ), always using both ethoxy- and methoxycarbonyl-nitrene ( 2a and 2b ). With 2a , (E)-azobenzene ( 14 ) was converted only to a single stereoisomer of 1-ethoxycarbonyl-2,3-diphenyl-azimine ( 17 ) and both stereoisomers of azo(p-toluene) ( 15 or 16 ) reacted to give the same stereoisomer of 1-ethoxycarbonyl-2,3-di(p-tolyl)-azimine ( 18 ).     

Studies on quinazolinones. 2. Synthesis of 2-(4-benzylpiperazin-1-ylmethyl)-2,3-dihydro-5H-oxazolo[2,3–6]quinazolin-5-one and -2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one

To search for novel antihypertensive heterocycles in the condensed quinazoline series, two representative compounds were synthesized via a suitable reaction sequences. Treating anthranilonitrile with allyl isocyanate gave 2-(allylureido)benzonitrile ( 10 ) in a quantitative yield. Compound 10 was cyclized to 3-allylquinazoline-2(1H, 4(3H)-dione ( 11 ). Bromination of 11 in carbon tetrachloride converted it into the corresponding 3-(2,3-dibromopropyl) derivative ( 12 ) in 92% yield. Ring closure of 12 was effected by the action of alkali to afford 2-bromomethyl-2,3-dihydro-5H-oxazolo[2,3-b]quinazolin-5-one ( 13 ). The title compound, 2-(4-benzylpiperazin-1-ylmethyl)-2,3-dihydro-5H-oxazolo[2,3-b]quinazolin-5-one ( 7 ) could be obtained by a reaction of either 12 or 13 with 1-benzylpiperazine respectively. Starting from the readily available 3-allyl-2H-thioxoquinazolin-4(3H)-one ( 16 ) via the analogous reactions gave the 2-bromomethyl-2,3-dihydro-5H-thiazolo[2,3-b]-quinazolin-5-one ( 19 ) in good yield. However, the reaction of 19 with 1-benzylpiperazine provided another target compound, 2-(4-benzylpiperazin-1-ylmethyl)-2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one ( 8 ) only in poor yield (8%). As major product, the dehydrobrominated compound, 2-methylene-2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one ( 22 ) was isolated. A preliminary pharmacological evaluation revealed that both compounds 7 and 8 are devoid of the antihypertensive activity.     

Isomeric Dioxodihydro-1H-Benzo[b]thiophenoindole Synthesis and Properties

The synthesis and properties of new heterocyclic systems are described: isomeric 2,3-dioxo-2,3-dihydro-1H-benzo[b]thiopheno[2,3-g]-, 1,2-dioxo-1,2-dihydro-1H-benzo[b]thiopheno[3,2-e]-, and 2,3-dioxo-2,3-dihydro-1H-benzo[b]thiopheno[2,3-f]indoles. The reduction of the latter to the corresponding unsubstituted benzo[b]thiophenoindoles depends on both the nature of the reducing agent and the reaction conditions.     

Quinoxaline-2,3(1H,4H)-dithione: Synthesis and reactions

Quinoxaline-2,3(1H,4H)-dithione can be synthesized efficiently through the thionation of quinoxaline-2,3(1H,4H)-dione with phosphorous pentasulfide. It can also be obtained by reaction of 2,3-dichloroquinoxaline with thiourea or sodium hydrogen sulfide. The most common reactions of quinoxaline-2,3(1H,4H)-dithione involve deprotonation and electrophilic attack at the sulfur atoms to give various substituted derivatives and poly-fused heterocyclic ring systems. The current review aims to provide a survey of the developments in quinoxaline-2,3(1H,4H)-dithione chemistry until 2016.     

Synthesis of 2,3-dihydro-5H-oxazolo[2,3-B]quinazolin-5-ones

Iodide-catalyzed ring expansion of 2-[(1-aziridinylcarbonyl)amino]benzoic acid methyl ester (2) gave 2,3-dihydro-5H-oxazolo[2,3-b]quinazolin-5-one (3) in quantitative yield. Treatment of the dimethyl analog of 2 (9) with sodium iodide in acetone gave a mixture of the 2,3-dihydro-2,2-dimethyl- (10) and 2,3-dihydro-3,3-dimethyl-5H-oxazolo[2,3-b]quinazolin-5-ones (11). However, rearrangement of 9 with sulfuric acid produced only 10. Synthesis of 11 by another route for comparison is described, and the known syntheses of 2,3-dihydro-5H-oxazolo[2,3-b]quinazolin-5-ones are reviewed.