Alkylation of 4,5-dichloropyridazin-6-one with α,ω-dibromoalkanes or 4,5-dichloro-1-(ω-bromoalkyl)pyridazin-6-ones

Alkylations of 4,5-dichloropyridazin-6-one (1) with dibromoalkanes 2 or 3 in the presence of potassium carbonate or tetrabutylammonium bromide/potassium hydroxide were investigated under restricted condition. Reactions of 1 with 2 or 3, except for 2b and 3b , in the presence of potassium carbonate or tetrabutylammonium bromide/potassium hydroxide gave only the N-alkylation products 3 and/or 4. Alkylation of 1 with 2b or 3b in the presence of potassium carbonate yielded the N-alkylation products 3b and/or 4b and the O-alkylation product 5 as the main product, whereas treatment of 1 with 2b or 3b in the presence of tetrabutylammonium bromide/potassium hydroxide afforded selectively the N-alkylation products 3b and/or 4b.     

Retro-ene reactions. III. Alkylation of 4,5-dichloro-1-hydroxymethylpyridazin-6-ones: Synthesis of 4,5-dichloro-1-(ω-phthalimido and saccharin-2′-ylalkyl)pyridazin-6-ones

4,5-Dichloro-1-(ω-phthalimido and saccharinyl-2′-ylalkyl)pyridazin-6-ones were synthesized from 4,5-dichloro-1-hydroxymethylpyridazin-6-one and the corresponding N-(ω-haloalkyl)phthalimides and saccharins via a fragmentation of retro-ene type.     

Synthesen von ω-substituierten ω-Nitrocarbonsäureestern aus α-Nitrocycloalkanonen

Synthesis of ω-Nitroalkanoates Substituted in ω-Position from α-Nitrocycloalkanones α-Nitrocycloalkanones substituted in α-position by a functionalized alkyl residue underwent ring opening to the corresponding chain derivatives by intermolecular nucleophilic attack; ω-nitroalkanoates substituted in ω-position were obtained (Scheme 1). The so formed methyl 6-nitro-9-oxodecanoate ( 3 ) was used to prepare methyl 8-(2-methyl-1,3-dioxolan-2-yl)octanoate ( 15 ), an intermediate in the synthesis of the sex phermone of the honey bee.     

Nucleophilic substitution in 1-alkyl-4,5-dichloro-3-nitropyridazin-6-ones

Treatment of 1-alkyl-4,5-dichloro-3-nitropyridazin-6-one with C-nucleophiles and with ambident nucleophiles (2-azahetarylacetonitriles) leads to a selective substitution of a chorine atom by the quaternary carbon atom of the carbanion formed from a substituted acetonitrile. The pK_a of the CH-acid 2-(1-alkyl-5-chloro-3-nitro-6-oxo-1,6-dihydro-4-pyridazinyl)malononitrile was determined by potentiometric titration. Reaction of 2-(1-alkyl-5-chloro-3-nitro-6-oxo-1,6-dihydro-4-pyridazinyl)-2-hetarylacetonitriles with primary amines gives 6,7-dihydro-1H-pyrrolo[2,3-d]pyridazin-7-ones. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 556–564, April, 2006.     

The structure of 6-tert-butyl-4,5-dichloro-3-ethyl-4,5-dihydro-2,1-benzoisoxazole

X-ray structural analysis revealed that the product of the reaction of 3,6-dialkyl-substitutedN-oxo-2,1-benzoisoxazolinium sulfate with hydrochloric acid is 6-tert-butyl-4,5-dichloro-3-ethyl-4,5-dihydro-2,1-benzoisoxazole.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 862–864, May, 1994.     

Reaction of 4,5-dichloro-3-nitropyridazin-6-one with dimethylchloromethyleneammonium chloride

3,4,5-Trichloropyridazin-6-one, 3,4,5,6-tetrachloropyridzine and 4,5-dichloro-3-(N,N-dimethylamino)-pyridazin-6-one were synthesized from 4,5-dichloro-3-nitropyridazin-6-one and dimethylchloromethylene-ammonium chloride selectively.     

Cyclization reactions of ω-tosyloxy-1-alkynyl- and ω-tosyloxy-1-alkenylborates and their ω-halo analogues

The reaction of trialkylboranes with ω-tosyloxy-1-lithio-1-alkynes can induce transfer of an alkyl group from the boron atom to the alkynyl carbon atom with concomitant formation of four- through six-membered carbocycles via intramolecular displacement of the ω-tosyloxy group. The stereoselectivity of the reaction, however, is low (anti/syn≃1.6–1.7). The corresponding reaction of ω-halo- or ω-tosyloxy-1-alkenylborates also gives exocyclic alkenes via 1,2-migration-cyclization followed by dehydroboration. In the cases of cyclopropanation, cyclopropylcarbinyl-to-homopropargyl rearrangement rather than dehydroboration takes place. Diphenylzirconocene reacts similarly with 6-lithio-5-hexynyl tosylate to give phenylmethylenecyclopentane in 45% yield. On the other hand, attempts to induce a similar migration with phenyl derivatives of Y, V, Cr, and Mn have led to < 5–10% yields of the same cyclization product.     

Retro-ene reaction. V. Functionalization of 4,5-dihalopyridazin-6-ones using 1-hydroxymethyl-4,5-dihalopyridazin-6-ones as 1–0, 3-n, 5–0 ene-adducts

Functionalization of 1-hydroxymethyl-4,5-dihalopyridazin-6-ones via a retro-ene reaction with some nucleophiles gave regioselectively only 5-halo-4-substitutedpyridazin-6-ones.     

Synthesis of 4,5-dichloro-1-(4,5-dichloropyridazin-3-yl)pyridazin-6-one

This paper presents the synthesis of 4,5-dichloro-1-(4,5-dichloropyridazin-3-yl)pyridazin-6-one from 4,5-dichloropyridazin-6-one.     

The reaction of aromatic α,β-unsaturated ketones with 4,5-diamino-1,6-dihydropyrimidin-6-ones

The reaction of 4,5-diamino-1,6-dihydropyrimidin-6-ones 1 with one equivalent of the chalcones 2 leads in an acidic medium to the formation of the 2,4-diaryl-2,3,6,7-tetrahydro-1H-pyrimido[4,5-b][1,4]diazepin-6-ones 3a-m . The structure elucidation of the products is based on detailed nmr investigations including selective ¹³C[¹H] decoupling experiments.     

Specifically (π → π*)-Induced Cyclohexenone Reactions 6-Benzylbicyclo [4.4.0]dec-1-en-3-ones

6-Benzylbicyclo [4.4.0]dec-1-en-3-one ( 9 ) and the 2-methyl homologue ( 10 ) underwent a (γ → α )-1, 3-benzyl shift to the β,γ-unsaturated ketones 21 and 22 , respectively, when excited in the π π* absorption band. The quantum yield was ca. 0.1 at 254 nm for the formation of both products in alkane solvents. These reactions occur specifically from the S₂(π, π*) state in competition with its decay to the S₁(n, π*) and T states. The triplet reaction of 9 , initiated by n → π* irradiation and by sensitization, was a double-bond shift to 20 , whereas no identifiable product was observed from 10 under these conditions. Direct and acetone-sensitized irradiations of 21 and 22 resulted in oxadi-π-methane rearrangements to mixtures of syn- and anti- 30 and syn- and anti- 31 , respectively.     

Syntheses of oxazolo[4,5‐c]pyridine and 6‐azaindole

The preparation of oxazolo[4,5‐c]pyridine and 6‐azaindole from 4‐bromo‐3‐pivaloylaminopyridine ( 8 ) is reported. The oxazolopyridine 2‐tert‐butyl‐oxazolo[4,5‐c]pyridine ( 9 ) was successfully prepared from 8 in 78% yield by a new base/TBAB promoted non‐catalyzed microwave cyclisation strategy (10 min) or, alternatively, in 54% yield by conventional heating (48 hrs) and CuI catalysis. The 6‐azaindole 2‐phenyl‐1‐(trimethylacetyl)‐6‐azaindole ( 13 ) was prepared from 8 in a two step procedure, including a Sonogashira coupling reaction.     

A Study on the Intramolecular Mitsunobu Reaction of N6‐(ω‐Hydroxyalkyl)adenines

The cyclization of N ⁶‐(ω‐hydroxyalkyl)adenines with a N⁶H‐group leads to N⁶,N1 ring closure regardless of the method of the cyclization that was used. Five‐membered to eight‐membered rings were obtained using NBS/PPh₃; however, under Mitsunobu conditions, the eight‐membered fused purine was not formed. Surprisingly, the cyclization of N ⁶‐methyl‐N ⁶‐(4‐hydroxybutyl)adenine only leads to N⁶,N7 ring closure using both methods.     

Photochemische Umwandlungen, 41 [1] 3ω → 3 π-Isomerisierungen von Monohetero-trishomobenzol-derivaten. Vorläufige mitteilung

The all-cis-oxa- and azatrishomobenzene diesters 4a and 4b resp. undergo thermally a very clean 3ω → 3π isomerization reaction yielding the heterocyclonona-2, 5, 8-triene derivatives 6a and 6b resp. (E_a = 27.4 and 26.5 kcal/mole). In contrast, the cis, cis, trans-oxatrishomobenzene diester 9 is stable up to 170°. Some applications and limitations of this 3ω → 3π-route to iso- and heterocyclononatriene derivatives are discussed.     

β‐Turn Analogues in Model αβ‐Hybrid Peptides: Structural Characterization of Peptides Containing β2,2Ac6c and β3,3Ac6c Residues

The effect of gem‐dialkyl substituents on the backbone conformations of β‐amino acid residues in peptides has been investigated by using four model peptides: Boc‐Xxx‐β^2,2Ac₆c(1‐aminomethylcyclohexanecarboxylic acid)‐NHMe (Xxx=Leu ( 1 ), Phe ( 2 ); Boc=tert‐butyloxycarbonyl) and Boc‐Xxx‐β^3,3Ac₆c(1‐aminocyclohexaneacetic acid)‐NHMe (Xxx=Leu ( 3 ), Phe ( 4 )). Tetrasubstituted carbon atoms restrict the ranges of stereochemically allowed conformations about flanking single bonds. The crystal structure of Boc‐Leu‐β^2,2Ac₆c‐NHMe ( 1 ) established a C₁₁ hydrogen‐bonded turn in the αβ‐hybrid sequence. The observed torsion angles (α(?≈?60°, ψ≈?30°), β(?≈?90°, θ≈60°, ψ≈?90°)) corresponded to a C₁₁ helical turn, which was a backbone‐expanded analogue of the type III β turn in αα sequences. The crystal structure of the peptide Boc‐Phe‐β^3,3Ac₆c‐NHMe ( 4 ) established a C₁₁ hydrogen‐bonded turn with distinctly different backbone torsion angles (α(?≈?60°, ψ≈120°), β(?≈60°, θ≈60°, ψ≈?60°)), which corresponded to a backbone‐expanded analogue of the type II β turn observed in αα sequences. In peptide 4 , the two molecules in the asymmetric unit adopted backbone torsion angles of opposite signs. In one of the molecules, the Phe residue adopted an unfavorable backbone conformation, with the energetic penalty being offset by a favorable aromatic interaction between proximal molecules in the crystal. NMR spectroscopy studies provided evidence for the maintenance of folded structures in solution in these αβ‐hybrid sequences.     

Oxidative Coupling of αω,-Di(cyclopentadienyl)alkane-diides

The Cu^II-induced oxidative coupling of αω,-di(cyclopentadienyl)alkane-diides 6 (n = 2–5) has been shown to proceed mainly by an intermolecular pathway to give polymers 8 , while the yield of intramolecular coupling 6 → 7 strongly decreases with increasing number n of C-atoms of the alkyl chain (Scheme 3). For n = 2, intramolecular coupling may be considerably enhanced by replacing the H-atoms of the CH₂CH₂ bridge of 6a (n = 2) by Me groups. In this case, intramolecular couplings 11 → 20 (Scheme 7) and 22 → 23 + 24 (Scheme 8) are accomplished with a total yield of 59% and 54%, respectively. All the intramolecular couplings investigated so far proceed stereoselectively to give the C₂-symmetrical cyclohexanes 7a, 20 and 23 with a fixed chair conformation. These results are easily explained, if a conformational equilibrium E ? F is operative in which large substituents R are assumed to enhance the gauche-conformation F which is the favored conformation for intramolecular couplings. Bridged dihydropentafulvalenes 20 and 23 are quantitatively rearranged to the thermodynamically favored bridged pentafulvenes 27 and 28 under base or acid catalysis, respectively (Scheme 9).     

α,ω-Disubstituted polymethylpolyphosphonates and polyphenylpolyphosphonates from condensation polymerization

Condensation polymerization of phosphonates through formation of P? O? P linkages has been achieved by (1) volatilization of methyl chloride from mixtures of CH₃P(O)Cl₂ with CH₃P(O)(OCH₃)₂; (2) volatilization or chemical removal of water from CH₃P(O)(OH)₂; and (3) volatilization of HCl from mixtures of CH₃P(O)Cl₂ with CH₃P(O)(OH)₂ or C₆H₅P(O)Cl₂ with C₆H₅P(O)(OH)₂. Depending on the proportions of the reagents, the polymerization products consist of various mixtures of chain molecules of the type \documentclass{article}\pagestyle{empty}\begin{document}${\rm X \hbox{--} P}({\rm O})({\rm R})\rlap{--}[{\rm O \hbox{--} P}({\rm O})({\rm R})\rlap{--}]_n {\rm X}$\end{document} for R = CH₃ and X = OCH₃, Cl, or OH, or for R = C₆H₅, x = Cl or OH. ³¹P nuclear magnetic resonance (NMR) was used to investigate both the polymethylpolyphosphonates and the polyphenylpolyphosphonates; and ¹H NMR of the CH₃P and CH₃O moieties was also used to study the polymethylpolyphosphonates. In the methoxyl-terminated polymethylpolyphosphonates, which was the system studied most extensively, no detectable amounts of cyclic molecules were found at equilibrium, but a crystalline methylphosphonic anhydride, CH₃PO₂, exhibited some ring structures. The equilibrium size distributions gave evidence that the sorting of the mono- and difunctional phosphorus-based units making up the oligomeric chains is affected by neighboring units. Kinetic measurements demonstrated that the condensation polymerization is a complicated process involving considerable scrambling of terminal groups with bridging oxygen atoms.     

Structural Factors Affecting the Basicity of ω-Pyridylalkanols, ω-Pyridylalkanamides and ω-Pyridylalkylamines

The present paper describes the preparation by conventional methods (when not available commercially) and the pK_a-determination of the α-, β- and γ-isomers of pyridylethanamide, 3-pyridylpropanamide. 4-pyridylbutanamide, 5-pyridyl-pentanamide, pyridylmethanol, 2-pyridylethanol, 3-pyridylpropanol, 4-pyridyl-butanol, 5-pyridylpentanol, pyridylmethylamine, 2-pyridylethylamine, 3-pyridyl-propylamine, 4-pyridylbutylamine, and 5-pyridylpentylamine. While a field effect accounts for many variations in pK_a as a function of chain length, marked inductive effects are operative in some methyl and ethyl homologs. The pK_a-decreasing influence of an intramolecular H-bond is also apparent in some lower homologs belonging to the α-series.     

Bifunctional even-electron ions. II. Fragmentation behaviour of aliphatic ω-hydroxy and ω-methoxy methoxonium ions

Bifunctional methoxonium ions \documentclass{article}\pagestyle{empty}\begin{document}$ {\rm R} -\mathop {\rm C}\limits^ + ({\rm OCH}_3 ) - ({\rm CH}_2 )_{\rm n} - {\rm OH}({\rm b}) $\end{document} and \documentclass{article}\pagestyle{empty}\begin{document}$ {\rm R} - \mathop {\rm C}\limits^ + ({\rm OCH}_3 ) - ({\rm CH}_2 )_{\rm n} - {\rm OCH}_3 ({\rm c}) $\end{document} (c) show as the main reactions those caused by functional group interaction, as has already been found for the analogous hydroxonium ions (g). Although there are similarities in the fragmentation behaviour of the isomeric ions b and g, their fragmentation pathways are different, proving b and g as distinct species. The dominant primary fragmentation for b and c is loss of CH₃OH. The hydrogen migrations prior to this reaction have been established by deuterium labelling. The findings on the fragmentation behaviour of the bifunctional methoxonium ions have been extended to the general behaviour of hydroxy and alkoxy substituted alkoxonium ions.     

天然产物 6-脱氧-6氨基葡萄糖甘油糖脂的合成

天然氨基甘油糖脂sn-1,2-dipalmitoyl-3-(N-palmitoyl-6-dehydroxy-6-amino-α-glucosyl)glycerol 3 和 sn-1-palmitoyl-2-myristoyl-3-(N-stearoyl-6-dehydroxy-6-amino-α-glucosyl)glycerol 4 通过简便有效的合成策略首次被合成。其关键步骤为：三氯亚胺酯糖基供体 10 与 (S)-isopropyleneglycerol 在乙醚溶液中发生糖苷化反应,立体选择性的生成3-O-(2,3,4-tri-O-benzyl-6-dehydroxy-6-benzyloxycarbonylamino-α-D- glucopyranoyl)-1,2-O-isopropylene-sn- glycerol 7。中间体 7 经过脱除丙酮叉、与不同的脂肪酸缩合、脱除保护基和选择性的在氨基上酰化,最终得到目标化合物 3 和 4。