硒催化羰基化合成1,3,4-噻二唑-2-氨基甲酸酯

以非金属硒作为催化剂,以CO替代剧毒光气作为羰基化试剂,以O₂作为氧化剂,通过2-氨基-1,3,4-噻二唑与醇以"一锅法"方式发生硒催化氧化羰基化反应,提出了一种成本低、原子经济性高、合成路线简短及环境相对友好的合成1,3,4-噻二唑-2-氨基甲酸酯类化合物的新方法.研究了反应温度、醇的用量、压力及碱的种类等对合成1,3,4-噻二唑-2-氨基甲酸酯的影响,在优化反应条件下,2-氨基-1,3,4-噻二唑可与一系列醇顺利发生羰基化反应,以45%~90%的收率得到1,3,4-噻二唑-2-氨基甲酸酯类化合物.     

苯并噻唑-2-甲醛合成方法的改进

以邻氨基苯硫酚为原料,先与羟基乙酸反应合成2-羟甲基苯并噻唑,然后通过氧化反应生成苯并噻唑-2-甲醛。对比了几种氧化剂的效果,发现二氧化锰氧化的效果最好。优化的反应条件为,2-羟甲基苯并噻唑与二氧化锰的摩尔比为1∶8,回流反应8h,产率可达90.2%。该方法适合苯并噻唑-2-甲醛及其衍生物的大规模生产。     

硒催化2-氨基苄醇氧化羰基化合成1,4-二氢-2H-3,1-苯并噁嗪-2-酮

1,4-二氢-2H-3,1-苯并噁嗪-2-酮作为一种重要的母体骨架广泛存在于生物活性化合物中。此外,在有机合成中它可作为经受热脱羧生成氮杂-邻二亚甲基苯的有效工具。文献报道的合成1,4-二氢-2H-3,1-苯并噁嗪-2-酮的方法有：2-氨基苄醇与光气或其替代物反应,钯或硫催化的2-氨基苄醇与 CO的羰基化反应,钯或硒催化的2-硝基苄醇与 CO的羰基化反应,钯催化的2-叠氮基苄醇直接羰基化反应或2-叠氮基苄醇的氮杂-维悌希(aza-Wittig)/杂累积多烯调节的环合反应,苯并呋喃酮的胺解-霍夫曼重排反应,硼氢化锂还原1,2-二氢-3,1-苯并噁嗪-2,4-二酮,以及2-羟甲基苯基氨基甲酸酯的分子内亲核取代反应。上述合成方法存在原料毒性高或成本高且来源不便、原子经济性低、有腐蚀性废物或 CO2排放、CO利用率低、催化剂昂贵且难以循环使用、反应步骤较多等缺陷,因此发展绿色、高效、经济的合成新途径具有重要意义。本文采用廉价易得的非金属硒作催化剂,用 CO作羰基化试剂, O2作氧化剂,通过硒催化2-氨基苄醇的氧化羰基化反应直接合成了目标产物1,4-二氢-2H-3,1-苯并噁嗪-2-酮。通过考察反应时间、反应温度、催化剂硒的用量、助催化剂种类及用量、CO和 O2的比例及溶剂种类等影响因素,得到了优化的反应条件,目标产物收率最高可达87%。实验证实,该 Se/CO催化体系具有相转移催化功能。反应前硒以粉末形式存在于反应体系中,为多相体系;反应开始后,硒粉参与羰基化反应形成可溶活性化合物,从而成为均相体系;反应完成后硒粉经氧化可重新从反应介质中沉淀析出,又变为多相体系。因此,该体系既实现了高效的均相催化反应,又便于催化剂分离回收,且回收的硒可重复使用,其催化活性基本保持不变。结合相关文献,我们提出了该反应的机理：在助催化剂三乙胺存在下,硒首先与 CO反应原位生成羰基硒,然后羰基硒先后接受2-氨基苄醇中氨基和羟基的亲核进攻生成目标产物,同时释放出硒化氢,硒化氢再被 O2氧化为硒,从而进入下一轮催化循环反应。总之,我们成功开发出一条绿色、高效、经济的1,4-二氢-2H-3,1-苯并噁嗪-2-酮合成新途径。用廉价易得且能循环使用的硒替代贵金属钯作催化剂,用 CO替代剧毒光气或其衍生物作羰基化试剂, O2作氧化剂,硒催化的2-氨基苄醇氧化羰基化反应可顺利进行,以87%的良好收率得到目标产物,具有成本低、原子经济性高、CO利用率高、步骤简短、无腐蚀性废物或温室气体 CO2排放、无光气使用及环境相对友好等优点。     

6-取代苯并噻唑-2-氨基硫代磷酸二烷基酯的合成

用6-位取代的2-氨基苯并噻唑与三氯硫磷反应,合成了3个苯并噻唑-2-氨基硫代磷酰二氯,并由此合成了9个苯并噻唑-2-氨基硫代磷酸二烷基酯.讨论了苯并噻唑环上取代基对反应的影响和产物中硫代磷酸酯的烷基的空间效应对反应的影响.所合成的部分化合物对人喉鳞状细胞癌(Hep-2)具有一定的抑制能力.     

新型2-苯并噻唑磺酰脲氨基酸及其甲酯衍生物的合成与抗肿瘤活性

以2-巯基苯并噻唑为原料,经弱氧化和氨化制得2-苯并噻唑次磺酰胺（2）; 2经高锰酸钾氧化制得2-苯并噻唑磺酰胺（3）; 3与氯甲酸乙酯反应制得2-苯并噻唑磺酰胺甲酸乙酯（4）; 4与L-氨基酸甲酯反应制得一系列2-苯并噻唑磺酰脲氨基酸甲酯（6a~6j）; 6经水解合成了10个新型的2-苯并噻唑磺酰脲氨基酸（7a~7j）,其结构经¹H NMR, IR和ESI-MS表征。并研究了6和7对Cdc25B的抑制活性。结果表明:在用药浓度为20 μg·mL^-1时,6c, 6j, 7d, 7h和7j对Cdc25B抑制活性较好,抑制率分别为78.1%, 71.2%, 65.6%, 57.2%和65.9%。     

新有机试剂4-(2-苯并噻唑偶氮)焦棓酚的合成、性能和分析应用

本文以2-氨基苯并噻唑为原料,经重氮化后与焦棓酚偶联合成了4-(2-苯并噻唑偶氮)焦棓酚,用乙醇重结晶精制。并用元素分析、波谱等鉴定了结构。测定了其离解常数和质子化常数。研究了该试剂的一般性质、多配位显色反应,发现其与Mo(Ⅵ)、W(Ⅵ)、Ti(Ⅳ)等的显色反应在CTMAB和CPB等阳离子表面活性剂存在下有高的灵敏度。     

2-二氟溴甲基-1,3-苯并噻唑的简便合成

本文应用二氟溴乙酸作为二氟溴甲基的合成子,实现了2 巯基芳胺与二氟溴乙酸的缩合反应合成2-二氟溴甲基-1,3-苯并噻唑。该反应以5当量二氟溴乙酸,氯苯为溶剂,于100 ℃下与2-巯基芳胺反应18~40 h,产率高达88%。目标产物通过核磁共振和高分辨质谱表征。该反应条件温和,是对现有合成2-二氟溴甲基-1,3-苯并噻唑的良好补充。     

荧光素的全合成

设计了一条新的萤火虫荧光素(6)的全合成路线.以对甲氧基苯胺为起始原料,经酰胺化、硫代、水解、铁氰化钾氧化等反应构筑苯并噻唑环得到6-甲氧基苯并噻唑-2-甲酸(2).首次采用一锅法对2进行酰氯-酰胺化后,经脱水制得关键中间体2-氰基-6-甲氧基-苯并噻唑(4);4经脱甲基、与D-半胱氨酸盐酸水合物反应合成了6,总收率20%,100%ee.其结构经UV,1H NMR,FT-IR和MS表征.     

1-(2-苯并噻唑基)-5-(2-苯基-1,2,3-三唑基)-3-芳基-2-吡唑啉衍生物的合成及其荧光性能

以2-苯基-1,2,3-三唑基-4-甲醛为原料,与苯乙酮或取代苯乙酮发生羟醛缩合生成相应的查尔酮；再与2-肼基苯并噻唑反应,合成了5个含1,2,3-三唑基、苯并噻唑基的新型吡唑啉衍生物，其结构经¹H NMR、 IR和元素分析表征。荧光性能研究结果表明：该类化合物具有良好的荧光性,其最大发射波长在427～444 nm,荧光强度大小与衍生物中不同的取代基有关     

S-烃基-1-烃基-3-[4-(苯并噻唑-2-巯基)苯基]异硫脲的合成及生物活性

以2-巯基苯并噻唑(1)为原料,经缩合和还原得到2-(4-氨基苯硫基)苯并噻唑(3),再与异硫氰酸苯甲酰酯或异硫氰酸烃基酯反应得到取代硫脲(5和7),最后与卤代烃反应得到20个新的S-烃基-1-烃基-3-[4-(苯并噻唑-2-巯基)苯基]异硫脲化合物(6和8),其结构经IR,1H NMR,MS及元素分析确证.初步的药理试验表明,20个目标化合物均有不同程度的iNOS抑制活性,化合物8a,8b,8c,8e,8f,8i,8j和8k的iNOS抑制活性强于阳性对照药氨基胍,其中化合物8j的iNOS抑制活性比氨基胍强26倍多.     

Synthesis of naphtho[2',3':4,5]imidazo[2,1-<Emphasis Type="Italic">b</Emphasis>][1,3]-thiazole-5,10-dione and naphtho[2',3':4,5]imidazo-[2,1-<Emphasis Type="Italic">b</Emphasis>][1,3]benzothiazole-7,12-dione

The reaction of 2,3-dibromo-1,4-naphthoquinone with 2-aminothiazole in MeONa/MeOH at 60oC for 3 h gave naphtho[2',3':4,5]imidazo[2,1-b][1,3]thiazole-5,10-dione in 64% yield. The reaction of 2,3-dibromo-1,4-naphthoquinone with 2-aminobenzothiazole under the above-mentioned conditions gave 2-(benzo[d]thiazol-2-ylamino)-3-bromonaphthalene-1,4-dione in 64% yield, which on treatment with Na/THF or NaN₃/acetone under reflux conditions gave naphtho[2',3':4,5]imidazo[2,1-b][1,3]- benzothiazole-7,12-dione in 69 and 56% yields, respectively.     

Research on heterocyclic compounds. XXI. Synthesis of imidazo[2,1-b]benzothiazole and imidazo[2,1-b]thiazole derivatives

The reaction of some 2-aminobenzothiazoles and 2-aminothiazoles with ethyl 3-bromo-4-oxopentanoate was investigated with the aim to obtain the corresponding imidazo[2,1-b]benzothiazole and imidazo[2,1-b]-thiazole derivatives, respectively. In some cases, two unexpected side products were obtained together with the required compound and their structures were elucidated: e.g., 2-aminobenzothiazole reacted with ethyl 3-bromo-4-oxopentanoate to give ethyl 2-methylimidazo[2,1-b]benzothiazole-3-acetate together with ethyl imi-dazo[2,1-b]benzothiazole-2-propionate and ethyl 3-(benzothiazol-2-yl)amino-4-oxopentanoate.     

Cyclometalated palladium pre-catalyst for N-alkylation of amines using alcohols and regioselective alkylation of sulfanilamide using aryl alcohols

Simple pyrazole based palladacycle-phosphine with a high turnover has been developed and applied for the N-alkylation of amines and sulfanilamide using alcohols as substrates by hydrogen borrowing strategy. N-alkylation of primary and secondary amines resulted in high isolated yields at 100–130 °C, under solvent free conditions. More challenging secondary aliphatic as well as aromatic alcohols were also successfully utilized as alkylating agents under similar reaction conditions. The turn over number reached up to 43000 for N-benzylation of aniline using benzyl alcohol. Notably, regioselective N-alkylation of 2-aminobenzothiazole and 4-aminobenzenesulfonamide to the corresponding 2-N-(alkylamino)azoles and 4-amino-(N-alkyl)benzenesulfonamides using alcohols as alkylating agents have been achieved using our new pre-catalyst-phosphine system.     

Pd/light-accelerated atom-transfer carbonylation of alkyl iodides: applications in multicomponent coupling processes leading to functionalized carboxylic acid derivatives

The atom-transfer carbonylation reaction of various alkyl iodides thereby leading to carboxylic acid esters was effectively accelerated by the addition of transition-metal catalysts under photoirradiation conditions. By using a combined Pd/hν reaction system, vicinal C-functionalization of alkenes was attained in which α-substituted iodoalkanes, alkenes, carbon monoxide, and alcohols were coupled to give functionalized esters. When alkenyl alcohols were used as acceptor alkenes, three-component coupling reactions, which were accompanied by intramolecular esterification, proceeded to give lactones. Pd-dimer complex [Pd(2)(CNMe)(6)][PF(6)](2), which is known to undergo homolysis under photoirradiation conditions, worked quite well as a catalyst in these three- or four-component coupling reactions. In this metal/radical hybrid system, both Pd radicals and acyl radicals are key players and a stereochemical study confirmed the carbonylation step proceeded through a radical carbonylation mechanism.     

Palladium-Catalyzed Low Pressure Carbonylation of Allylic Alcohols by Catalytic Anhydride Activation

A direct carbonylation of allylic alcohols has been realized for the first time with high catalyst activity at low pressure of CO (10 bar). The procedure is described in detail for the carbonylation of E-nerolidol, an important step in a new BASF-route to (−)-ambrox. Key to high activities in the allylic alcohol carbonylation is the finding that catalytic amounts of carboxylic anhydride activate the substrate and are constantly regenerated with carbon monoxide under the reaction conditions. The identified reaction conditions are transferrable to other substrates as well.     

色谱法同时测定羰化反应尾气中的O2、CO、CO2

提出用特制活性炭填充柱分离,热导检测器检测,以外标法定量,同时测定O2、CO、CO2.探讨了该方法的校正因子、各组分的线性相关性及微量氧气的分离和定量等.在选定的色谱条件下,O2与CO的分离度达1.7,各组分的相对标准偏差＜0.18%,绝对误差＜0.04%.     

Toward transition metal-catalyzed carbonylation of methanol without HI as copromoter: catalytic exocyclic carbonylation of cycloimino esters

[reaction: see text] Initial studies of a rare exocyclic C-O bond carbonylation are reported. Under the catalysis of Co(2)(CO)(8) in the absence of HI as the copromoter, cycloimino esters are carbonylated to afford N-acyllactams in high yields under relatively mild conditions (100-160 degrees C and 200-1000 psi). The reaction is interesting because it opens up the possibility of carbonylation of alcohols in the absence of HI.     

Pd/Light‐Accelerated Atom‐Transfer Carbonylation of Alkyl Iodides: Applications in Multicomponent Coupling Processes Leading to Functionalized Carboxylic Acid Derivatives

The atom‐transfer carbonylation reaction of various alkyl iodides thereby leading to carboxylic acid esters was effectively accelerated by the addition of transition‐metal catalysts under photoirradiation conditions. By using a combined Pd/hν reaction system, vicinal C‐functionalization of alkenes was attained in which α‐substituted iodoalkanes, alkenes, carbon monoxide, and alcohols were coupled to give functionalized esters. When alkenyl alcohols were used as acceptor alkenes, three‐component coupling reactions, which were accompanied by intramolecular esterification, proceeded to give lactones. Pd‐dimer complex [Pd₂(CNMe)₆][PF₆]₂, which is known to undergo homolysis under photoirradiation conditions, worked quite well as a catalyst in these three‐ or four‐component coupling reactions. In this metal/radical hybrid system, both Pd radicals and acyl radicals are key players and a stereochemical study confirmed the carbonylation step proceeded through a radical carbonylation mechanism.     

Novel palladium(II) complex containing a chelating anionic N-O ligand: efficient carbonylation catalyst

[reaction: see text] A novel palladium(II) complex containing chelating anionic pyridine-2-carboxylato and labile tosylato ligands is a highly efficient catalyst for the carbonylation of organic alcohols and olefins to carboxylic acids/esters. Carbonylation of primary, secondary, and tertiary alcohols as well as linear and functionalized terminal olefins was studied. In all cases remarkable activity and selectivity were observed. The catalyst is stable under reaction conditions even in the absence of excess phosphine ligands.