精喹禾灵中间体6-氯-2-喹喔啉醇的合成

综述了6-氯-2-喹喔啉醇的合成方法以及国内外研究动态和进展，参考文献20篇。6-氯-2-喹喔啉醇是-种重要的有机化工原料，是合成新型高效除草剂精喹禾灵原药的重要中间体，其合成一般通过6-氯-2-喹喔啉醇-4-氧化物的选择性还原来制取。     

Regioselective synthesis of asymmetrically substituted 2-quinoxalinol salen ligands

Diamino-2-quinoxalinols are reacted with salicylaldehyde derivatives to produce 2-quinoxalinol imines regioselectively as one isomer in good yield. Regioselectivity has been determined through the use of isotopic 15N labeling experiments. The 2-quinoxalinol imines may then be reacted without further purification with additional salicylaldehyde derivatives to yield asymmetrically substituted 2-quinoxalinol salens.     

Allylic C-H activations using Cu(II) 2-quinoxalinol salen and tert-butyl hydroperoxide

Using a Cu(II) 2-quinoxalinol salen complex as the catalyst and tert-butyl hydroperoxide (TBHP) as the oxidant, allylic activations of olefin substrates can be converted to the corresponding enones or 1,4-enediones. Excellent yields can be achieved (up to 99%) within a very short reaction time and with great tolerance for additional functional groups. Possible mechanistic pathways have been characterized using Raman spectroscopy, cyclic voltammetry, and theoretical calculations.     

An efficient method for solution-phase parallel synthesis of 2-quinoxalinol salen Schiff-base ligands

A solution-phase parallel method for the synthesis of 2-quinoxalinol salen ligands was designed and optimized. The synthesis begins with commercially available 1,5-difluoro-2, 4-dinitrobenzene (DFDNB) and employs a sequence of five straightforward and high-yielding reaction steps. Simple laboratory techniques with low sensitivity to water or air for solution-phase parallel reactions were coupled with convenient workup and purification procedures to give high-purity and yield a small ligand library of 20 compounds. The final step, a Schiff-base condensation of an aldehyde with the diaminoquinoxaline results in a new category of ligands for metal coordination or of potential bioactivity, based on the skeleton 2,2'-(1E,1'E)-(quinoxaline-6,7-diylbis(azan-1-yl-1-ylidene))bis(methan-1-yl-1-ylidene)diphenol. The approach described here is easily adaptable for parallel synthesis of a larger library.     

One-pot metal templated synthesis for the preparation of 2-quinoxalinol salen metal complexes

Metal complexes of 2-quinoxalinol salen (salqu) ligands can be prepared in a one-pot metal templated synthesis resulting in significantly enhanced yields than if the ligand were prepared and isolated prior to introducing the metal for complexation. Using this method, 12 salqu metal complexes have been prepared and characterized from +2 metal ions.     

Enantioselective Organocatalytic Cascade Approach to Different Classes of Benzofused Acetals

A novel enantioselective organocatalytic strategy is presented for the synthesis of tetrahydrofurobenzofuran and methanobenzodioxepine natural product core structures. The strategy is based on a pair of divergent reaction pathways in which hydroxyarenes react with γ‐keto‐α,β‐unsaturated aldehydes, catalyzed by a chiral secondary amine. One reaction pathway, which leads to chiral 5,5‐fused acetals with two stereocenters—the tetrahydrofurobenzofuran scaffolds—proceeds in moderate yields and up to 96 % ee. The other reaction pathway provides 5,6‐bridged methanobenzodioxepine scaffolds with three stereocenters in moderate to good yields and up to 95 % ee. The reaction is remarkable as it can proceed with catalyst loadings as low as 0.25 mol %, providing one of the highest known turnover numbers in iminium ion catalysis. Furthermore, the hemiacetal tetrahydrofurobenzofuran can undergo functionalizations including reduction, oxidation, and allylation. Finally, the effects involved in the substrate control for the divergent pathways, based on both experimental and computational studies, have been investigated. A model involving steric, electronic and stereoelectronic interactions is discussed to rationalize the observed selectivities.     

Parallel approach for solution-phase synthesis of 2-quinoxalinol analogues and their inhibition of LPS-induced TNF-alpha release on mouse macrophages in vitro

A parallel solution-phase synthesis of 2-quinoxalinol analogues is described. The key step-simultaneous reductions of m-Ar(NO(2))(2) to m-Ar(NH(2))(2) was investigated extensively. We obtained preliminary pharmacological activity of those analogues for the inhibition of LPS-induced TNF-alpha release on mouse macrophage in vitro. Two compounds revealed inhibitory activity, with IC(50) values of 0.40 microM (7-amino-6-[(3-methoxypropyl)amino]-3-methyl-2-quinoxalinol) and 2.2 microM (7-amino-6-[(3-butoxypropyl)amino]-3-methyl-2-quinoxalinol), respectively.     

Tandem RCM-Pauson-Khand reaction for access to tricycles in one step

Starting from conveniently designed dienynes complexed to cobalt, a tandem RCM-intramolecular Pauson-Khand reaction yields tricyclic compounds. The methodology allows the synthesis of 6,5,5 and 7,5,5 systems.     

Exceptionally pyramidalized olefins: A theoretical study of the cyclopropenyl fused tricycles Tricyclo

RHF, MP2, and TCSCF ab initio theory and B3LYP, B3PW91, and SVWN density functional theory were used to study the series of cyclopropenyl-fused tricycles 9-12. In each of 9-12, the cyclopropenyl double bond is exceptionally pyramidalized (butterfly angle psi approximately 41-50 degrees ) with both endo and exo bent isomers. In the norbornyl systems (9 and 10), the endo bent isomers are more stable than the exo bent isomers, whereas in the bicyclo[2. 2.2]octadiene 12 the reverse is true with the exo bent isomer being the low energy form. The activation barriers for the endo/exo interconversions are calculated to be relatively low (DeltaH() approximately 6-13 kcal/mol).     

Design and synthesis of novel tricycles based on 4H-benzo[1,4]thiazin-3-one and 1,1-dioxo-1,4-dihydro-2H-1lambda6-benzo[1,4]thiazin-3-one

This paper reports our recent efforts to develop novel tricycles based on 4H-benzo[1,4]thiazin-3-one ( 2) and 1,1-dioxo-1,4-dihydro-2H-1lambda(6)-benzo[1,4]thiazin-3-one (3) using 1,5-difluoro-2,4-dinitrobenzene (1). All of these tricycles integrate two privileged structures into one skeleton, including 3,8-dihydro-5-thia-1,3,8-triaza-cyclopenta[b]naphthalene-7-one (4, 10, 12), 5,5-dioxo-3,5,6,8-tetrahydro-5lambda(6)-thia-1,3,8-triaza-cyclopenta[b]naphthalene-7-one (5, 11), 3,8-dihydro-5-thia-1,2,3,8-tetraaza-cyclopenta[b]naphthalene-7-one (6), 5,5-dioxo-3,5,6,8-tetrahydro-5lambda(6)-thia-1,2,3,8-tetraaza-cyclopenta[b]naphthalene-7-one (7), 3,8-dihydro-1H-5-thia-1,3,8-triaza-cyclopenta[b]naphthalene-2,7-dione (8), and 5,5-dioxo-3,5,6,8-tetrahydro-1H-5lambda(6)-thia-1,3,8-triaza-cyclopenta[b]naphthalene-2,7-dione (9). A typical library of scaffold 5 was synthesized in a parallel solution-phase manner and analyzed by HPLC-UV-MS or HPLC-UV-ELSD method.     

Divergent Carbocatalytic Routes in Oxidative Coupling of Benzofused Heteroaryl Dimers: A Mechanistic Update

Mildly thermal air or HNO₃ oxidized activated carbons catalyse oxidative dehydrogenative couplings of benzo[b]fused heteroaryl 2,2’-dimers, e.g., 2-(benzofuran-2-yl)-1H-indole, to chiral 3,3’-coupled cyclooctatetraenes or carbazole-type migrative products under O₂ atmosphere. DFT calculations show that the radical cation and the Scholl-type arenium cation mechanisms lead to different products with 2-(benzofuran-2-yl)-1H-indole, being in accord with experimental product distributions.     

An efficient route to polynitrogen-fused tricycles via a nitrene-mediated N-N bond formation under microwave irradiation

The synthesis of unprecedented fused azaheterocyclic ring systems is described. Tricycles with either a central pyrazole or a triazole ring were obtained via a nitrene-mediated reaction of nitro bis(hetaryl) derivatives in the presence of triethylphosphite. The cyclization proceeded with complete chemoselectivity for the desired N-N bond formation and was completed within minutes under microwave activation. The key nitro bicycles were synthesized using either Stille couplings or aromatic nucleophilic substitution.     

Cu(II) 2-quinoxalinol salen catalyzed oxidation of propargylic,benzylic, and allylic alcohols using tert-butyl hydroperoxide in aqueous solutions

The synthesis of carbonyl compounds by oxidation of alcohols is a key reaction in organic synthesis. Such oxidations are typically conducted using catalysts featuring toxic metals and hazardous organic solvents. Considering green and sustainable chemistry, a copper(II) complex of sulfonated 2-quinoxalinol salen (sulfosalqu) has been characterized as an efficient catalyst for the selective oxidation of propargylic, benzylic, and allylic alcohols to the corresponding carbonyl compounds in water when in combination with the oxidant tert-butyl hydroperoxide. The reactions proceed under mild conditions (70 °C in water) to produce yields up to 99% with only 1 mol % of catalyst loading. This reaction constitutes of a rare example of propargylic alcohol oxidation in water, and it makes this process greener by eliminating the use of hazardous organic solvents. Excellent selectivity was achieved with this catalytic protocol for the oxidation of propargylic, benzylic, and allylic alcohols over aliphatic alcohols. The alcohol oxidation is thought to go through a radical pathway.     

Regiochemistry of addition of aminoheterocycles to α-cyanocinnamonitriles: formation of aza-bridged bi- and tricycles

The additions of various five-membered ring aminoheterocycles to α-cyanocinnamonitriles were studied. Regiochemistry of product formation can in most cases be controlled by choosing the appropriate electrophile. An α-cyanocinnamonitrile with an additional β-leaving group normally provides products arising from initial attack of the ring amino group, while exo attack predominates in the case of the parent α-cyanocinnamonitrile. Aminopyrazole and aminoindazole provide only exo products with either electrophile. Product assignments were made via X-ray and 2D NMR methods; these assignments serve as a benchmark to several literature references and to future investigations of conjugate additions of these nucleophiles.     

An efficient synthesis of fused tricycles with a benzene core via intramolecular double ring-closing enyne metathesis

A double enyne metathesis reaction has been developed for the efficient synthesis of tricyclic products with a benzene core in good yields. By this protocol, bisannulated benzenes with different ring sizes may be simultaneously constructed from the corresponding precursors in just ‘one shot’.     

Synthesis of angularly fused cyclopentanoids and analogous tricycles via photoinduced ketyl radical/radical anion fragmentation-cyclization reactions

Angular fused tricycles were synthesized through intramolecular tandem fragmentation-cyclization reactions by photochemically induced electron transfer (PET) of tricyclic α-cyclopropyl ketones with an unsaturated side chain at the position γ to the carbonyl group. The reactions resulted in regioselective cleavage of a β-cyclopropyl bond with formation of angular fused tricyclic ring systems via ketyl radical/radical anions as reactive intermediates. In general, triethylamine (TEA) was used as a strong reducing reagent in acetonitrile. The preferred regioselectivity of the cyclization step (exo vs endo) depending on the substitution pattern at the quaternary carbon center (Cβ′) of the tricyclic α-cyclopropyl ketones was investigated. In addition, we also checked a two-step pathway for the synthesis of angular dioxa-triquinanes including photolysis of an allyloxy-substituted cyclopenta[c]furanone derivative and subsequent β-cleavage of the resulted dioxa-[4.5.5.5]fenestrane under reductive PET conditions.