有机胂化合物的研究(ⅩⅤ)——溴化(4-乙氧羰基苯基)甲基三苯鉮的合成及其与α,β-不饱和酮的相转移反应

黄耀曾等曾报道了环丙烷衍生物的合成方法,但在碱存在下用季鉮盐直接与α,β-不饱和酮进行相转移反应合成环丙烷衍生物的方法尚未见报道。我们用常法制得溴化(p-乙氧羰基苯基)亚甲基三苯基鉮(1),进而与系列α,β-不饱和酮(2_(a-f))在二氯甲烷和50％氢氧化钠液相体系中于室温反应得到相应的环丙烷衍生物(3_(a-f)),为合成这类化合物提供了一条简便     

转移催化(PTC)反应研究III.1-^1^4C,1,1-二溴-2-苯基环丙烷及其取代物的合成

本文报道了^1^4C-溴仿的制备,并在相转移催化条件下由它合成了五个^1^4C-标记偕二溴环丙烷衍生物2a-e.2a-e与非标记产物3a-e的纯度对照,表明均已达到化学纯.     

氯甲基化-二苯并-14-冠4的合成

以邻苯二酚和1,3-二溴丙烷为原料,高产率(50.24％)地制备了二苯并-14-冠-4(1);1在多聚甲醛和浓盐酸存在下与四丁基溴化胺反应,合成了氯甲基化-二苯并-14-冠4,其结构经1H NMR和IR表征.     

相转移催化(PTC)反应研究——Ⅲ.1-~(14)C,1,1-二溴-2-苯基环丙烷及其取代物的合成

本文报道了~(14)C-溴仿的制备,并在相转移催化条件下由它合成了五个~(14)C-标记偕二溴环丙烷衍生物2a～e。2a～e与非标记产物3a～e的纯度对照,表明均已达到化学纯。     

新型手性季鏻盐的合成

以(S)-联萘酚为原料,与三氟甲磺酸酐反应制得联萘酚三氟甲磺酸酯(2);2在Ni(dppp)Cl2催化下与碘甲烷格氏试剂反应得2,2’-二甲基联萘(3);3经溴代反应得2,2’-二溴甲基联萘4;4与1,3-双(二苯基膦)丙烷(dppp)在甲苯中回流合成了一个新型的联萘酚衍生的双中心手性季鏻盐,其结构经1H NMR,31P NMR和FT-IR表征。     

5(R)-(l-氧基)-2(5H)-呋喃酮与溴代丙二酸二乙酯的反应

研究了5(R)-(l-?氧基)-2(5H)-呋喃酮与溴代丙二酸二乙酯在无水K2CO3和相转移催化剂四丁基溴化铵(TBAB)存在下,以乙腈为溶剂,在80℃下的反应及产物结构特征.在上述条件下得到了预期的具有两个乙酯基的手性环丙烷/丁内酯衍生物3,同时还得到了含有一个乙酯基的手性环丙烷/丁内酯化合物5以及少量的含溴产物6.通过对产物结构分析,提出了产物形成的可能机理.     

(R)-α-烷基糠胺的不对称合成

本文通过(+)-樟脑缩呋喃甲亚胺的不对称烷基化反应, 合成了(R)-α)-烷基糠胺。反应的非对映选择性经1H NMR测定为5～67%(d.e)。用1, 3-二碘丙烷和α, α-二溴邻二甲苯作烷基化试剂, 得到预期的双亚胺烷基产物, 而用1,2-二溴乙烷时,却给出偶联产物。     

新型手性咪唑鎓环番的合成及对氨基酸的对映选择性识别

以L-氨基酸为手性源, 合成了一系列新型手性咪唑鎓环番, 并进行了结构表征. 在碱性条件下, L氨基酸和乙二醛、甲醛缩合生成了(S)-2-(1-咪唑)羧酸钠, 转化为甲酯后与乙二胺进行胺解反应制得开链手性咪唑二酰胺, 然后与二溴化合物在高稀淡技术和无水条件下进行季铵化关环反应, 再进行阴离子交换制得目标分子(4~6). 以手性咪唑鎓环番为主体分子, 研究了对氨基酸及其衍生物的对映选择性识别作用.     

2-(2-苯并呋喃基)-6-氯-3-喹啉甲酸衍生物的简便合成

以6-氯-2-氯甲基-3-喹啉甲酸乙酯(1)为底物,在无水碳酸钾作为缚酸剂、乙腈作为溶剂、聚乙二醇-400作为相转移催化剂的条件下分别与水杨醛(2a~2i)、邻羟基苯乙酮(2j~2o)及2-羟基-1-萘醛(2p)经"三步一锅法"在超声辅助下回流反应,成功的合成了2-(2-苯(萘)并呋喃基)-6-氯-3-喹啉甲酸衍生物(3a~3p).所合成化合物的结构均通过红外光谱、核磁共振氢谱、核磁共振碳谱和高分辨质谱得以证实.     

(2S)-(+)-2-溴-1-(6'-甲氧基-2'-萘基)丙-1-酮的不对称合成

以(2R,3R)-酒石酸二甲酯为手性辅助剂,6-甲氧基-2-丙酰基萘经缩酮化、溴化铜不对称溴化、水解等反应合成了(2S)-2-溴-1-(6'-甲氧基-2'-萘基)丙-1-酮。总收率94%。     

(Z)-3-丁烯基-4-羟基苯酞的合成

（Ｚ）－３－丁烯基－４－羟基苯酞的合成李绍白,王志伟,方小平,李裕林（兰州大学应用有机化学国家重点实验室,兰州,７３００００）关键词（Ｚ）－３－丁烯基－４－羟基苯酞,苯酞,３－丙基－５－羟基异香豆素,异香豆素,合成（Ｚ）－３－丁烯基－４－羟基苯酞（１...     

光学活性噻吗洛尔的合成

噻呜洛尔(Timolol)是一种新型的β-受体阻断剂。化学名为S-(-)-1-叔丁胺基-3-[(4-吗啉代-1,2,5-噻二唑-3-基)氧]-2-丙醇顺丁烯二酸盐。     

Reaktionen von α-Chlorcarbonsäurechloriden mit Trialkylaminen

The condensation of α,α-dichloropropionyl chloride (IVa) and of trichloroacetyl chloride (IVb) with α-chloropropionyl chloride (Ia) in the presence of triethylamine led to two acid chloride enol-esters, both as mixtures of cis- and trans-isomers, namely 1, 2-dichloropropenyl α,α-dichloropropionate (Va) and 1, 2-dichloropropenyl trichloroacetate (Vb). A mixture of triethylamine and trichloroacetyl chloride produced an oxidation-reduction reaction to give 48% 1, 2, 2, 2-tetrachloroethyltrichloroacetate (VIII) and 69% 1-diethylamino-4, 4, 4-trichloro-1-butene-3-one (IX). Basic hydrolysis of IX led to 43% of glutaconic acid (XIII). Tripropylamine reacted in the same way with trichloroacetyl chloride to yield 1-dipropylamino-2-methyl-4, 4, 4-trichloro-but-1-ene-3-one (XIX) which was readily hydrolyzed in acid solution to α-trichloroacetyl-propionaldehyde (XX).     

(+)-2-甲基-4-戊烯酸的合成

丙二酸二乙酯与碘甲烷反应生成二乙基甲基丙二酸酯(1). 由(1)进行皂化和脱羧反应制备2-甲基-4-戊烯酸(4).用一种新的拆分剂葡辛胺拆分(4)得到(+)-2-甲基-4-戊烯酸.     

Synthesis and reactivity of 3-(trichlorogermyl)propanoic acid and 3-(triphenylgermyl) propanoic acid

3-(Trichlorogermyl)propanoic acid (la) reacts with phenylmagnesium bromide in malar ratio 1:4 to give 3-(triphenylgermyl)propanoic acid (2a).In the compounds la and 2a theβ-carboxylic functional group shows some unusual properties when they react with excess of phenylmagnesium bromide.The compound la reacts with phenylmagnesium bromide in molar ratio 1:5 to give phenyl 2-(triphenylgermyl)ethylketone (3a) and in molar ratio 1:6 to give l,l-diphenyl-3-(triphenylgermyl)propanol (4a).The compound 2a reacts with phenylmagnesium bromide in molar ratio 1:2 to give 3a and in molar ratio 1:3 to give 4a also.Dehydration of the compound 4a with dilute hydrochloric acid seems especially easy.Moreover,the compound la reacted with phenylmagnsium bromide in molar ratio 1:6,then the mixture was treated with dilute hydrochloric acid to give 1,1-diphenyl-3-(triphenylgermyl)-1-propene (5a) in one pot reaction.Alkyl Ge-C bond in the compound 5a can be cleaved selectively by lithium aluminium hydride ( LiAlH4) in good yiel     

Epoxidation and reduction of DHEA, 1,4,6-androstatrien-3-one and 4,6-androstadien-3beta,17beta-diol

Dehydroepiandrosterone (DHEA) reacted with m-chloroperoxybenzoic acid(m-CPBA) to form 3beta-hydroxy-5alpha,6alpha-epoxyandrostan-17-one (1), but it did not react with 30% H2O2. 1,4,6-Androstatrien-3,17-dione (2) was obtained from DHEA and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in dioxane. Compound 2 was reacted with 30%H2O2 and 5% NaOH in methanol to give 1alpha,2alpha-epoxy-4,6-androstadien-3,17-dione (3),which was stereoselectively reduced with NaBH4 to form 1alpha,2alpha-epoxy-4,6-androstadien-3beta,17beta-diol (7) and reacted with Li metal in absolute ethanol-tetrahydrofuran mixture to give 2-ethoxy-1,4,6-androstatrien-3,17-dione (8). Compound 2 was also epoxidized with m-CPBA in dichloromethane to afford 6alpha,7alpha-epoxy-1,4-androstadien-3,17-dione (4),which was reacted with NaBH4 to synthesize 6alpha,7alpha-epoxy-4-androsten-3beta,17beta-diol (9).Compound 4 was reduced with Li metal in absolute ethanol-tetrahydrofuran mixture to form 7beta-ethoxy-6alpha-hydroxy-1,4-androstadien-3,17-dione (10). Compound 2 was reduced with NaBH4 in absolute ethanol to form 4,6-androstadien-3beta,17beta-diol (5), which was reacted with 30% H2O2 to give the original compound, but which reacted with m-CPBAto give 4beta,5beta-epoxy-6-androsten-3beta,17beta-diol (6).     

Synthesis of pyridazino[4,5-b]indole derivatives from 2-(3-carboxy-1-methylindole)acetic acid anhydride

2-(3-Carboxy-1-methylindole)acetic acid anhydride ( 1 ) reacts with aryldiazonium salts to give 85–95% of the corresponding α-hydrazono anhydrides 2 . Treating 2 with boiling hydrazine hydrate in xylene, the respective 2-aryl-4-carbohydrazido-5-methyl-1-oxo-1,2-dihydro-5H/-pyridazino[4,5-b]indoles 3 were obtained (47–67%), and these compounds characterized as the respective benzylidene derivatives 4 . Compounds 2 react with amines (aniline, morpholine, piperidine) to give the respective 2-(3-carboxy-1-methylindole)aceta-mide 5 or the respective 2-aryl-4-carboxamido-5-methyl-5H-pyridazino[4,5-b]indole 6 , the product obtained depending on the structure of the aryl substituent. Boiling 2b (aryl = 4-chlorophenyl) with 5% sodium hydroxide gave (80%) 2-(3-carboxy-1-methylindole)acetic acid ( 7 ). Hydrolysis of 2b gave a mixture of 7 and 2-(3-carboxy-1-methylindolyl)-2-(4-chlorophenylhydrazono)acetic acid ( 8 ).     

(S)-2-氨基-1,1-二苯基-1-丙醇的合成和外消旋Droxidopa前体的拆分

(S)-2-氨基-1,1-二苯基-1-丙醇是一种合成多种手性助剂的重要中间体,也用于外消旋屈昔多巴前体化合物的拆分。从价廉易得的L-丙氨酸出发,通过四步反应制得,总收率55.6%L-丙氨酸经甲酯化,苄氧羰基保护制得的L-2-苄羰基氨基丙酸甲酯与苯基溴化镁反应制得(S)-2-苄氧羰基氨基-1,1-二苯基-1-丙醇。是在5%Pd/C催化加氢下脱除苄氧羰基得到标题化合物。该制备方法涉及的中间体及目标化合物易于纯化,总收率高且重现性好。我们用制得的氨基醇能成功地拆分外消旋苏式屈昔多巴前体化合物3-3,4-二苄氧苯基)-N-苄氧羰基丙氨酸。     

Reactions of 1,2-Dimethyl-5-nitroimidazole,novel methods of conversion of the 2-Methyl group to a nitrile

1, 2-Dimethyl-5-nitroimidazole( 1 )and N,N-dimethylformamide dicyclohexylacetal gave the 2-(β-dimethylaminovinyl) analog 2 and with iodine and pyridine gave the 2-(1-pyridinium)methyl compound 3 . Benzoyl chloride-triethylamine and 1 led to benzoylation of the 2-methyl group to give ketone 9 as the enol benzoate. Nitrous acid or nitrosylsulfuric acid with 9 or its enol ester afforded the oximinoketone 10 which was cleaved with thionyl chloride to give 2-cyano-1-methyl-5-nitroimidazole ( 11 ) in high overall yield. 1-Ethyl-2-methylbenzimidazole ( 22 ) was converted to 2-cyano-1-ethylbenzimidazole ( 25 ) similarly. Reaction of 1 with ethyl oxalyl chloride and triethylamine afforded ethyl 1-methyl-5-nitro-2-imidazolepyruvate ( 19 ) as the enol oxalate. Nitrous acid and 19 gave the oximino pyruvate 20 which effervesced on mild heating to give 2-cyano-1-methyl-5-nitroimidazole ( 11 ). The preparation of 1-methyl-5-nitro-2-imidazoleacetonitrile ( 39 ) is reported.     

Synthesis of new chiral sulfinyldiacetic acid derivatives and attempt at chemoselective asymmetric Pummerer reaction

(R(S))-1 (85% ee) was prepared by utilizing a porcin pancreatic lipase-promoted hydrolysis of sulfinyldiacetic acid dimethyl ester (8) which was derived from thiodiacetic acid (7). (R(S))-1 (99% ee) and (S(S))-1 (99% ee) were readily obtained by methanolysis of (R(S),S)-12 and (S(S),S)-12 with MeONa in MeOH. (R(S),S)-12 and (S(S),S)-12 were furnished by chromatographic separation of the diastereomeric mixture, obtained by oxidation of thiodiacetic mono-carboxylic acid (11) with 30% H2O2 followed by dehydrative condensation of the resultant sulfinyldiacetic mono-carboxylic acid with 4(S)-isopropyl-1,3-thiazolidine-2-thione. (R(S))-1 (99% ee) was successively treated with (TMS)2NLi, Ac2O, and TMSOTf to give a major chiral-3 product in 75% ee and in a highly chemoselective manner (chiral-3:chiral-2=93:7).