1-硫代-1-磷杂-2,6,7-三氧杂双环[2.2.2]辛烷基-4-亚甲基硫醚及其亚砜的合成

本文通过Williamson反应, 合成了9个双环笼状硫代磷酸酯的硫醚衍生物3a～i. 以3b,3c为例研究了硫醚衍生物的还原性, 并合成相应的亚砜化合物4b,4c. 讨论了亚砜化合物的立体化学.     

1,2,4-三唑-3-硫醚衍生物的合成、晶体结构与神经氨酸酶抑制活性

设计并合成了一系列1,2,4-三唑-3-硫醚衍生物,目标化合物的化学结构经¹H NMR、¹³C NMR、质谱和元素分析确证;采用单晶X射线衍射法测定了(E)-4-(4-羟基-3-甲氧基苯基亚甲氨基)-5-乙基-4H-1,2,4-三唑-3-丙硫醚(1c)的晶体结构.目标化合物体外神经氨酸酶(Neuraminidase, NA, H1N1)抑制活性测试结果表明,大部分化合物1具有较好的NA抑制活性,其中(E)-4-(4-羟基-3-甲氧基苯基亚甲氨基)-5-乙基-4H-1,2,4-三唑-3-乙硫醚(1b)和1c的NA抑制活性最佳,其IC50值分别为(6.86±2.08)和(9.1±1.56)μg/m L.     

1-(取代硅基甲硫基)甲基-2,8,9-三氧杂-5-氮杂-1-硅杂双环[3.3.3]十一烷的合成与生物活性

2,8,9一三氧杂一5一氮杂司一硅杂双环［3．3．3」十一烷（Silatrane）衍生物是一类具有广泛生物活性的五配位有机硅化合物,自6O年代发现以来一直引起人们浓厚的兴趣,随着其1位硅原子上所连基团的变化,该类化合物可表现出通然不同的生物活性［’j．为寻找新的生物活性物质,本文在Silatranel位引入一类含硅甲硫醚基团,合成了11种新的Silatrane衍生物,并初步测定了其在农药、医药方面的生物活性;同时,在其质谱中发现存在罕见的重排裂解过程．合成方法如下：回实验部分1．l仪器与试剂BrukerAC－PZOO型NMR仪,CDCI。为溶剂,TM…     

1-氧代-1-磷杂-2, 6, 7-三氧杂双环[2.2.2]-4-含硫取代基辛烷 的合成

本文利用中间体1-氧代-1-磷杂2,6,7-三氧杂双环[2.2.2]-4-羟甲基辛烷(1)和1-氧代-1-磷杂-2,6,7-三氧杂双环[2.2.2]-4-氯甲酰基辛烷(3)分别与RSH或取代硫醇按步骤反应得到了相应的4-亚甲基硫醚(5a～f)、4-亚甲基亚砜(6a～f)、4-(氯代乙硫基)甲酰基(7)及4-(β-烷硫基)-α-硫代酯基(8a～i)的双环笼状磷酸酯新衍生物共22个。所有的化合物经元素分析、IR和^1HNMR得到了证实。     

1-(2’-烷硫基乙氧基)甲基尿嘧啶及其氧化物的合成

采用 3 0 %H2 O2 /DEAD的试剂组合 ,用于将硫醚及亚砜的衍生物氧化成砜类物质的反应 ,合成了1 ( 2 烷硫基乙氧基 )甲基尿嘧啶及其氧化物 ,产物结构经元素分析、1HNMR和IR进行表征 ,并研究了其抗癌活性     

1，3-二羟基丙酮衍生物的合成

以五氧化二磷为引发剂，二甲亚砜氧化1，3-二芳氧基(烷氧基)-2-丙醇化合物合成了一系列1，3-二羟基丙酮衍生物．通过IR和^H NMR对化合物进行了表征．     

对苯二酚-二(4-氧代-4-磷杂-3,5,8-三氧杂双环[2.2.2]辛基)甲酸酯的合成及表征

自1960年Verkade 等[1 ]首次合成了结构新颖的双环笼状磷酸酯以来,由于其高度对称的结构而引起人们的极大兴趣,具有生物活性的衍生物不断见诸报道[2～3 ].由于该化合物具备丰富的炭源(季戊四醇) 和酸源(磷酸),其衍生物逐渐成为无卤膨胀阻燃剂研究的热点之一.李昕等[4-5]以PEPA为中间体,合成了分子中同时具有三个笼状磷酸酯结构的化合物的三聚物(Trimer),结构对称性好,磷含量高,热稳定性和成炭性比较好.杨兴钰等[6]以PEPA为中间体,合成了8个双环笼状磷酸酯酰胺类化合物,该类化合物集酸源、炭源和气源于一体,应用于环氧树脂材料中具有良好的阻燃性.目前含有芳环结构的PEPA衍生物的合成鲜有报道.本研究课题以季戊四醇、三氯氧磷、浓硝酸、二氯亚砜和对苯二酚等为原料,合成了一种具有芳环结构、含磷量高、耐热性好、无卤等特点的PEPA衍生物对苯二酚-二(4-氧代-4-磷杂-3,5,8-三氧杂双环[2 2 2]辛基)甲酸酯.合成路线如下:1 实验部分1.     

3-氨基-7,8-二甲氧基香豆素及其衍生物的合成及抗氧化活性

合成了3-氨基-7,8-二甲氧基香豆素及其衍生物共11个化合物,其中3个化合物(2b、2d、2e)为新型香豆素芳酰胺类化合物。 通过猝灭1,1-二苯基-2-三硝基苯肼(DPPH)、2,2'-联氮二(3-乙基苯并噻唑-6-磺酸)二铵盐阳离子自由基(ABTS^+·)和羟自由基实验考察了所合成化合物的抗氧化活性,结果表明化合物2b对DPPH自由基、羟自由基的清除能力超出或接近对照品维生素C,而衍生物2a、2b和2c的抗氧化活性优于母体。 故酰化可提高3-氨基-7,8-二甲氧基香豆素的抗氧化性能,尤其是普遍提高了羟基自由基的清除能力。     

1,5-苯并硫氮杂 -β-内酰胺衍生物的不对称合成及晶体结构

用(-)-4R-苯基唑烷酮为手性诱导试剂,N-端保护的N-乙酰氯与1,5-苯并硫氮杂反应合成了5个具有光学活性的1,5-苯并硫氮杂 -β-内酰胺衍生物,并通过1H NMR,MS,IR,[α]20 1)和元素分析对此类化合物进行了表征,用X射线衍射法确定了产物Ⅱb的立体结构.晶体X射线衍射分析结果表明,化合物Ⅱ b属单斜晶系,P21 21 21空间群,晶胞参数:Mr=553.05,a=1.229 3(2)nm,b=2.602 6(5)nm.c=1.014 6(2)nm,β=90°,V=3.246 1 nm3,Z=4,Dc=1.312 g/cm3,F(000)=1 344,R1=0.058 4,wR2=0.114 0.该化合物分子中七元杂环为类椅式构象,四元环上连接的两个取代基在环的同侧.     

1-(2′-烷硫基乙氧基)甲基尿嘧啶及其氧化物的合成

采用30％H202／DEAD的试剂组合,用于将硫醚及亚砜的衍生物氧化成砜类物质的反应,合成了1-(2-烷硫基乙氧基)甲基尿嘧啶及其氧化物,产物结构经元素分析、1H NMR和IR进行表征,并研究了其抗癌活性.     

Synthesis of carbinoxamine via α-C(sp3)–H 2-pyridylation of O,S or N-containing compounds enabled by non-D–A-type super organoreductants and sulfoxide- or sulfide HAT reagents

The radical cations of tertiary amines (R₃N) have been well-established as the precursors of HAT reagents in photochemical transformations. Similarly, thiols and thioacids bearing SH groups have also been widely applied as HAT reagents. Despite the fact that sulfoxides (R₂SO) and sulfides (RSR) also bear lone pairs of electrons, these compounds have been barely reported as HAT reagents in photocatalysis. On the other hand, the α-C–H 4-pyridylation of O or N-containing compounds has been documented, whereas 2-pyridylation remains challenging. However, the antihistamine and anticholinergic agent carbinoxamine is an ether bearing 2-pyridyl, which has not been obtained by the existing α-photoarylation of ether. In this work, we report the discovery of a non-donor–acceptor (D–A) type organic photoreductant CBZ6 and sulfoxide/sulfide synergistically catalyzed general α-C(sp³)–H arylation of ethers, thioethers and amines. By using as low as 1 mol% of CBZ6 as a recyclable organic photoreductant and sulfoxides or sulfides as a new type of HAT reagent, the 2- or 4-pyridylation of O, N, or S-containing compounds has been accomplished. This is the first base-free version of α-C–H 2-/4-pyridylation of O, N, or S-containing compounds. It is the first example of sulfoxides or sulfides working as HAT reagents. It is also the first general method for photocatalytic HAT 2-pyridylation of various ethers, amines or thioethers.

We report the discovery of a non-donor–acceptor (D–A) type organic photoreductant CBZ6 and sulfoxide/sulfide synergistically catalyzed general α-C(sp³)–H arylation of ethers, thioethers and amines.     

Structural and mechanistic look at the orthoplatination of aryl oximes by dichlorobis(sulfoxide or sulfide)platinum(II) complexes

Structural and mechanistic aspects of orthoplatination of acetophenone and benzaldehyde oximes by the platinum(II) sulfoxide and sulfide complexes [PtCl(2)L(2)] (2, L = SOMe(2) (a), rac-SOMePh (b), R-SOMe(C(6)H(4)Me-4) (c), and SMe(2) (d)) to afford the corresponding platinacycles cis-(C,S)-[Pt(II)(C(6)H(3)-2-CR'=NOH-5-R)Cl(L)] (3, R, R' = H, Me) have been investigated. The reaction of acetophenone oxime with sulfoxide complex 2a in methanol solvent occurs noticeably faster than with sulfide complex 2d due to the fact that the sulfoxide is a much better platinum(II) leaving ligand than the sulfide. Evidence is presented that the orthoplatination is a multistep process. The formation of unreactive dichlorobis(N-oxime)platinum(II) cations accounts for the rate retardation by excess acetophenone oxime and suggests the importance of pseudocoordinatively unsaturated species for the C-H bond activation by Pt(II). A comparative X-ray structural study of dimethyl sulfoxide platinacycle 3b (R = R' = Me) and its sulfide analogue 3e (R = H, R' = Me), as well as of SOMePh complex 3c (R = H, R' = Me), indicated that they are structurally similar and a sulfur ligand is coordinated in the cis position with respect to the sigma-bound phenyl carbon. The differences concern the Pt-S bond distance, which is notably longer in the sulfide complex 3e (2.2677(11) A) as compared to that in sulfoxide complexes 3b (2.201(2)-2.215(2) A) and 3c (2.2196(12) A). Whereas the metal plane is practically a plane of symmetry in 3b due to the H-bonding between the sulfoxide oxygen and the proton at carbon ortho to the Pt-C bond, an S-bonded methyl of SOMePh and SMe(2) is basically in the platinum(II) plane in complexes 3c and 3e, respectively. There are intra- and intermolecular hydrogen bond networks in complex 3b. An interesting structural feature of complex 3c is that the two independent molecules in the asymmetric unit of the crystal reveal an extremely short Pt-Pt contact of 3.337 A.     

Tautomeric structure of 1-methyldihydropyridazino-[3,4-b]quinoxalines in solution

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 1 with ethyl 2-ethoxymethylene-2-cyano-acetate or ethoxymethylenemalononitrile gave 6-chloro-2-[2-(2-cyano-2-ethoxycarbonylvinyl)-1-methylhy-drazino]quinoxaline 4-oxide 3a or 6-chloro-2-[2-(2,2-dicyanovinyl)-1-methylhydrazino]quinoxaline 3b , respectively. The reaction of 3a with a base afforded 7-chloro-1-methyl-1,5-dihydropyridazino[3,4-b]quinoxaline 4 . From the NOE spectral data, the 1-methyldihydropyridazino[3,4-b]quinoxalines 2a, 2b and 4 were found to exist as the 1,5-dihydro form in a dimethyl sulfoxide or trifluoroacetic acid/dimethyl sulfoxide solution.     

双核有机锡配合物CH_2(SnPhBr_2)_2·2DMSO的合成及晶体结构

通过双 (苯基二溴化锡基 )甲烷CH2 (SnPhBr2 ) 2 与DMSO的配位反应或者双 (苯基二溴化锡基 )甲烷的双 (三唑 )甲烷配合物CH2 (SnPhBr2 ) 2 ·CH2 Tz2 与DMSO的配体取代反应 ,可以制得标题化合物。用X 射线衍射测定了该化合物的晶体结构。结果表明 ,该晶体属于单斜晶系 ,C2 /c空间群。分子式为C1 3H1 2 Br4Sn2 ·2 (C2 H6SO) ,Mr=881 .52 ,a =1 0 .0 4 0 (2 ) ,b =1 5.345(3) ,c =1 7.992 (4) ,β =1 0 5.99(3)°,V =2 665(1 ) 3,Z =4,Dc=2 .1 92Mg·m- 3,μ =7.9674mm- 1 ,1 31 4个可观测衍射点 (I≥ 3σ(I) ) ,最终结构偏离因子R =0 .0 4 2 ,Rw =0 .0 4 6。分子中 2个锡原子均为六配位的变形八面体构型 ,通过DMSO中的氧原子桥联 2个锡原子。     

On the stereospecific reduction of vinylsulfoxides with thepossibility of deuterium labeling

Upon treating triene sulfoxide 2 or 3 in the of methanol (internal proton source) in ether with -butyllithium, the reduced product 4b or 4c, respectively, is obtained with retention of configuration. A deuterium label can be incorporated by using methanol-0-d₁ as the internal proton source.     

Regioselective Alkylation of the Polyfunctional Nucleophile 1-(Methylthio)-3-triethylsilyloxypentadienyllithium

γ-Selective sulfenylation of the triethysilyloxypentadienyllithium 1 gave the versatile alkylthiodene 4 which on successive deprotonation and alkylation furnished with high regioselectivity the γ-products 6 . Fluoride-promoted silylether cleavage 6 → 7 may be followed by intramolecular [4 + 2]-addition 7c → 8 and sulfoxide elimination 8 → 9 . The conversions 7b → 12 and 7a → 17 demonstrate the feasibility of 5 to serve as an equivalent of the hypothetical β-deprotonated divinylketone 13 whose two enone units may be unmasked separately.     

Additive Pummerer reactions of vinylic sulfoxides. Synthesis of γ-hydroxy-α,β-unsaturated esters, α-hydroxyketones, and 2-phenylsulfenyl aldehydes and primary alcohols

Treatment of β-monosubstituted vinylic sulfoxides 1 with trifluoroacetic anhydride in dichloromethane gave excellent yields of 1,2-bis(trifluoroacetoxy)thioethers 6. Mildly basic methanolysis of 2-alkyl-substituted 6 gave α-hydroxyaldehydes 11 as monomer-dimer mixtures; similar treatment of the 2-aryl analogues afforded aryl (hydroxymethyl) ketones 12. Compounds 11 underwent Wittig reactions with methoxycarbonylmethylenetriphenylphosphorane to give high yields of γ-hydroxy-α,β-unsaturated esters 13, predominantly as the E-isomers. β-Monosubstituted vinylic sulfoxides 1 possessing a β-aryl group, and β-disubstituted vinylic sulfoxides 3 reacted with trifluoromethanesulfonic anhydride-sodium acetate in acetic anhydride to give 2-(phenylsulfenyl)acylals 14. These gave 2-phenylsulfenyl aldehydes 15 upon basic methanolysis, and the corresponding primary alcohols 16 on reduction with sodium borohydride. Reaction of both geometric isomers of enantiomerically pure vinylic sulfoxide 1o with TFAA gave racemic 6o as a mixture of diastereomers. Reaction of optically pure (E)- and (Z)-1p with trifluoromethanesulfonic anhydride-sodium acetate in acetic anhydride gave acylal 19 in 10.5 and 23% e.e., respectively.     

4‐Chloro‐3′‐methylsulfinyl‐5(6 or 8)‐nitro‐3,4′‐diquinolinyl sulfides

Reaction of 4‐chloro‐3′‐methylthio‐3,4′‐diquinolinyl sulfides 3, 9b, 9c with a nitrating mixture proceeds via the 3′‐methylthio group monooxidation and yields 3′‐methylsulfinyl diquinolinyl sulfides 4, 5b, 5c , respectively. Further treatment of 4 with a nitrating mixture followed as C₅‐ and C₈‐nitration and gives mixture of 5a and 5c. Treatment of 3′‐methylsulfinyl quinolines 6 and 7 with hydrochloric acid/potassium iodide system causes reduction of the sulfoxide group in 6 and 7 to the sulfide group yielding 8 , in case of 4‐methoxyquinolines 6 , hydrolysis of the 4‐methoxyquinoline moiety to the 4‐quinolinone moiety takes place simultaneously. The proton and carbon chemical shifts of 4 and 5a were completely assigned following COSY, HETCOR and INEPT or COLOC studies.     

Highly enantioselective construction of tertiary thioethers and alcohols via phosphine-catalyzed asymmetric γ-addition reactions of 5H-thiazol-4-ones and 5H-oxazol-4-ones: scope and mechanistic understandings

Phosphine-catalyzed highly enantioselective γ-additions of 5H-thiazol-4-ones and 5H-oxazol-4-ones to allenoates have been developed for the first time. With the employment of amino-acid derived bifunctional phosphines, a wide range of substituted 5H-thiazol-4-one and 5H-oxazol-4-one derivatives bearing heteroatom (S or O)-containing tertiary chiral centers were constructed in high yields and excellent enantioselectivities. The reported method provides facile access to enantioenriched tertiary thioethers/alcohols. The mechanism of the γ-addition reaction was investigated by performing DFT calculations, and the hydrogen bonding interactions between the Brønsted acid moiety of the phosphine catalysts and the “CO” unit of the donor molecules were shown to be crucial in asymmetric induction.