公开(公告)号：US07109362B2

公开(公告)日：2006-09-19

申请号：US10432455

申请日：2001-11-29

申请人： Martin Jochen Klatt ,  Markus Niebel ,  Joachim Paust

发明人： Martin Jochen Klatt ,  Markus Niebel ,  Joachim Paust

IPC分类号： C07B45/00 ,  A61K31/095 ,  C07D339/04

CPC分类号： C07D339/04

摘要： The present invention relates to a process for the preparation of R- and S-lipoic acid and R- and S-dihydrolipoic acid comprising(a) reaction of where MS is SO2—R′ and R and R′ independently of one another are C1–C6-alkyl, C3–C8-cycloalkyl, C3–C8-cycloalkylalkyl, aryl or aralkyl, with sodium sulfide and sulfur in methanol. The invention especially relates to processes for preparing pure R- or S-dihydrolipoic acid, which is either used directly or processed further to give R- and S-lipoic acid. The process also serves for the production of pharmaceuticals. The present invention further relates to a solution of sodium sulfide trihydrate and sulfur in methanol, the sulfur being present in a molar excess over the sodium sulfide trihydrate, and a kit which comprises the solution according to the invention.

摘要翻译： 本发明涉及制备R-和S-硫辛酸和R-和S-二氢硫辛酸的方法，其包括（a）其中MS为SO 2 -R'和R和 R'彼此独立地是C 1 -C 6 - 烷基，C 3 -C 8 - 环烷基 C 3 -C 8 - 环烷基烷基，芳基或芳烷基，与硫化钠和硫在甲醇中反应。 本发明特别涉及制备纯R-或S-二氢硫辛酸的方法，其可直接使用或进一步加工得到R-和S-硫辛酸。 该方法还用于生产药物。 本发明还涉及硫化钠三水合物和硫在甲醇中的溶液，所述硫以超过硫化钠三水合物的摩尔量存在，以及包含根据本发明的溶液的试剂盒。

公开(公告)号：US5582739A

公开(公告)日：1996-12-10

申请号：US126881

申请日：1993-09-27

申请人： Klaus Kaiser ,  Joachim Paust

发明人： Klaus Kaiser ,  Joachim Paust

IPC分类号： C07D307/62 ,  C02F1/52 ,  C02F1/58 ,  C07F9/655

CPC分类号： C07F9/65515 ,  Y10S210/906

摘要： A process for reducing the phosphate content in waste water from the preparation of salts of ascorbic acid 2-monophosphate comprisesA. treating the waste water from the crystallization of the metal salts of ascorbic acid 2-monophosphate with an alkali metal or alkaline earth metal hypochlorite, chlorine or H.sub.2 O.sub.2,andB. precipitating, at a pH of 9-12, the inorganic phosphate which has been produced from organically bound phosphorus and/or was present in the waste water, especially as calcium phosphate.

摘要翻译： 从制备抗坏血酸2-单磷酸盐的盐中降低废水中的磷酸盐含量的方法包括：用碱金属或碱土金属次氯酸盐对2-一磷酸抗坏血酸的金属盐进行结晶处理废水 ，氯或H 2 O 2，和B.在pH为9-12的条件下沉淀出由有机结合的磷生成的和/或存在于废水中，特别是作为磷酸钙的无机磷酸盐。

公开(公告)号：US5504230A

公开(公告)日：1996-04-02

申请号：US358113

申请日：1994-12-16

申请人： Michael John ,  Joachim Paust

发明人： Michael John ,  Joachim Paust

IPC分类号： C07C51/00 ,  C07C57/03 ,  C07C69/56 ,  C07C403/00 ,  C07C403/20 ,  C07F9/02 ,  C07F9/54

CPC分类号： C07C403/20 ,  C07F9/5435 ,  C07B2200/09 ,  C07C2101/16

摘要： A process for preparing 9-(Z)-retinoic acid from mother liquors from the industrial preparation of C.sub.15 -triarylphosphonium salts of the general formula I ##STR1## where R.sup.1 to R.sup.3 are each aryl and X.sup..crclbar. is halogen or (HSO.sub.4).sup..crclbar., in an organic solvent, which comprisesA. increasing the proportion of 9-(Z)-C.sub.15 -triarylphosphonium salt in the C.sub.15 -triarylphosphonium salts isolated from the mother liquor by treatment with isopropanol at elevated temperature, cooling and separating off the all-(E)-C.sub.15 -triarylphosphonium salt which has crystallized out,B. subjecting the resulting C.sub.15 -triarylphosphonium salt to a Wittig reaction with an alkyl .beta.-formylcrotonate of the general formula ##STR2## and C. hydrolyzing the resulting oily retinoic ester mixture in a C.sub.3 -C.sub.9 -alkanol, preferably in a propanol or butanol, precipitating the resulting 9-(Z)-retinoic acid where appropriate by adding methanol as crystals, with all-(E)-retinoic acid and other retinoic acid isomers remaining in the alkanolic solution.

摘要翻译： 从通式Ⅰ的C15-三芳基鏻盐的工业制备方法由母液制备9-（Z） - 视黄酸的方法，其中R 1至R 3各自为芳基，X（ - ）为卤素或 （HSO 4）（ - ），在有机溶剂中，其包括A.通过在高温下用异丙醇处理从母液中分离的C 15 - 三芳基鏻盐中增加9-（Z）-C15-三芳基鏻盐的比例，冷却 并分离已结晶的全 - （E）-C 15 - 三芳基鏻盐，B.将所得的C 15 - 三芳基鏻盐与通式为“IMAGE”的β-甲酰基巴豆酸烷基酯进行维蒂希反应，并将C.水解 得到的油状视黄酸酯混合物在C3-C9-链烷醇中，优选在丙醇或丁醇中，通过加入甲醇作为结晶，通过全 - （E） - 维A酸和其它物质沉淀得到的9-（Z） - 维A酸 视黄酸异构体残留在链烷醇溶胶中 小心

公开(公告)号：US5424465A

公开(公告)日：1995-06-13

申请号：US220495

申请日：1994-03-31

申请人： Michael John ,  Joachim Paust

发明人： Michael John ,  Joachim Paust

IPC分类号： C07C51/353 ,  C07C403/20

CPC分类号： C07C403/20 ,  C07B2200/09 ,  C07C2101/16

摘要： 13-(Z)-Retinoic acid is prepared bya) reacting 5-hydroxy-4-methyl-2(5H)-furanone with a [3-methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadienyl]triarylphosphonium salt andb) subsequently partially isomerizing the resulting mixture of 13-(Z)- and 11,13-di-(Z)-retinoic acid,where the reaction in step a) is carried out in the presence of lithium hydroxide as alkali metal hydroxide and in dimethylformamide as solvent at from +10.degree. to -9.degree. C. and/or the isomerization in step b) is carried out by irradiating the mixture of isomers obtained in a) in an organic solvent in the presence of a photosensitizer with light in the wavelength range from 200 to 600 nm.

摘要翻译： 通过a）使5-羟基-4-甲基-2（5H） - 呋喃酮与[3-甲基-5-（2,6,6-三甲基-1-环己烯-1-酮） （Z） - 和11,13-二 - （Z） - 视黄酸的混合物，其中步骤a）中的反应， 在作为碱金属氢氧化物的氢氧化锂和作为溶剂的二甲基甲酰胺存在下，在+ 10〜-9℃下进行，和/或步骤b）中的异构化是通过照射在 ）在光敏剂存在下在有机溶剂中，其中波长范围为200-600nm。

公开(公告)号：US5338888A

公开(公告)日：1994-08-16

申请号：US086028

申请日：1993-07-06

申请人： Joachim Paust ,  Wolfgang Krause

发明人： Joachim Paust ,  Wolfgang Krause

IPC分类号： B01J31/02 ,  C07B61/00 ,  C07C41/50 ,  C07C43/303 ,  C07C41/01 ,  C07C41/28

CPC分类号： C07C41/50

摘要： An improved process for preparing E,Z-butenedial bis(dialkyl acetals) by reacting the corresponding 2,5-dialkoxy-2,5-dihydrofurans with the corresponding lower alkanols in the presence of an acid at elevated temperature entails carrying out the reaction in the presence of approximately equimolar amounts of a trialkyl orthoformate and in the presence of catalytic amounts of a strong mineral acid or of a strong organic acid.

摘要翻译： 通过使相应的2,5-二烷氧基-2,5-二氢呋喃与相应的低级链烷醇在酸的存在下在升高的温度下反应来制备E，Z-丁二烯双（二烷基缩醛）的改进方法需要进行反应 存在大约等摩尔量的原甲酸三烷基酯，并且在催化量的强无机酸或强有机酸的存在下。

公开(公告)号：US4999437A

公开(公告)日：1991-03-12

申请号：US486755

申请日：1990-03-01

申请人： Walter Dobler ,  Joachim Paust ,  Roland Betz

发明人： Walter Dobler ,  Joachim Paust ,  Roland Betz

IPC分类号： C07F9/655

CPC分类号： C07F9/65515

摘要： Ascorbic acid 2-phosphate is prepared by reacting ascorbic acid or an ascorbic acid derivative with POCl.sub.3 in the presence of a tertiary amine in a suitable aqueous solvent at from -10.degree. to 25.degree. C. while maintaining a pH of about 8-13.5 with KOH during the entire phosphorylation reaction and then isolating the ascorbic acid 2-phosphate, by a process in which an aqueous solution of a magnesium compound is added to the reaction mixture obtained in the phosphorylation, without prior treatment with an ion exchanger, until the formation of crystalline KMg PO.sub.4 is complete, the KMgPO.sub.4 which is crystallized out is separated off, the resulting filtrate is evaporated down at a pH of from 6 to 11 and/or from 0.1 to 5 times the amount, based on the evaporated filtrate, of a lower primary alkanol or acetone is added and the stirred mixture is cooled until KCl has completely crystallized out, and the ascorbic acid phosphate is isolated in a conventional manner from the reaction solution obtained by separating off KCl and substantially freed from inorganic salts. It is particularly advantageous if the ascorbic acid 2-phosphate is isolated in the form of the novel potassium magnesium ascorbate 2-phosphate, which is also claimed.The process is particularly advantageous if the ascorbic acid derivative used is 5,6-isopropylideneascorbic acid which has been obtained by reacting ascorbic acid with acetone in the presence of oleum. The process is particularly important for the preparation of L-ascorbic acid 2-phosphate.

摘要翻译： 抗坏血酸2-磷酸酯通过使抗坏血酸或抗坏血酸衍生物与POCl 3在叔胺存在下，在-10℃至25℃的合适的水性溶剂中反应制备，同时保持约8-13.5的pH，同时用 KOH，然后通过将镁化合物的水溶液加入到磷酸化中获得的反应混合物中而不用离子交换剂进行预处理的方法分离出抗坏血酸2-磷酸酯，直到形成 结晶KMg PO4完成后，将结晶出来的KMgPO4分离出来，所得滤液按照蒸发滤液的6至11和/或0.1至5倍的pH蒸发掉， 加入低级主链烷醇或丙酮，将搅拌的混合物冷却直至KCl完全结晶出来，并以常规方式从得到的反应溶液中分离抗坏血酸磷酸酯 通过分离KCl并基本上从无机盐中除去。 特别有利的是，抗坏血酸2-磷酸酯以新的抗坏血酸钾2-磷酸2-钾的形式被分离，这也是要求保护的。 如果所使用的抗坏血酸衍生物是在发烟硫酸存在下使抗坏血酸与丙酮反应获得的5,6-异亚丙基抗坏血酸，该方法是特别有利的。 该方法对于制备L-抗坏血酸2-磷酸酯尤为重要。

公开(公告)号：US4544758A

公开(公告)日：1985-10-01

申请号：US508802

申请日：1983-06-28

申请人： Friedrich Vogel ,  Joachim Paust ,  Axel Nuerrenbach

发明人： Friedrich Vogel ,  Joachim Paust ,  Axel Nuerrenbach

IPC分类号： C07C17/16 ,  C07D311/72 ,  C07F3/02 ,  C07F9/143 ,  C07F9/54

CPC分类号： C07F9/5428 ,  C07C17/16 ,  C07D311/72 ,  C07F3/02 ,  C07F9/143

摘要： The invention relates to intermediate compounds having the general formula I ##STR1## in which R.sup.1 is H, an alkyl, arylalkyl or an aliphatic acyl radical, preferably a benzyl or acetyl group and wherein X and Y together span an additional bond between the X and Y carrying C atoms (Ia) or in which Y is OH and X is H (Ib) and in which the dotted line can represent an additional bond particularly [2R,1'Z,3'E,7'E]-6-benzyloxy-2,5,7,8-tetramethyl-2-(4',8',12'-trimethyl-trideca-1',3',7'-trien-1'-yl)chroman and 6-benzyloxy-2,5,7,8-tetramethyl-2-(1'-hydroxy-4',8',12'-trimethyl-trideca-3',7'-diene-1'-yl)chroman, as well as compounds and methods of preparing compounds having the general formula II ##STR2## in which Z is one of the groups ##STR3## wherein R.sup.2 is an alkyl group with 1 to 4 carbon atoms preferably CH.sub.3 or C.sub.2 H.sub.5, particularly (3,7,11-trimethyl-trideca-2,6,10-trien-1-yl)triphenylphosphonium chloride and (3,7,11-trimethyl-trideca-2,6,10-trien-1-yl) phosphoric acid dimethylester as well as methods for the preparation of (2R,4'RS,8'RS)-.alpha.-tocopherol and (all-rac)-.alpha.-tocopherol via the new intermediate product.

摘要翻译： 本发明涉及具有通式I（I）的中间体化合物，其中R 1为H，烷基，芳烷基或脂族酰基，优选苄基或乙酰基，并且其中X和Y一起跨越 X和Y携带C原子（Ia）或其中Y是OH，X是H（Ib），其中虚线可以代表额外的键，特别是[2R，1'Z，3'E，7'E] -6-苄氧基-2,5,7,8-四甲基-2-（4'，8'，12'-三甲基十三碳烯-1'，3'，7'-三烯-1'-基）苯并二氢吡喃酮 6-苄氧基-2,5,7,8-四甲基-2-（1'-羟基-4'，8'，12'-三甲基 - 三环-10a-3'，7'-二烯-1'-基）苯并二氢吡喃 ，以及制备具有通式II（II）的化合物的化合物和方法，其中Z是组ClMg之一; BrMg（IIa）; 其中R2是具有1至4个碳原子的烷基，优选CH 3或C 2 H 5，特别是（3,7,11-三甲基 - 十三碳-2,6,10-三烯-1-基）三苯基氯化鏻和 （3,7,11-三甲基 - 十三碳-2,6,10-三烯-1-基）磷酸二甲酯以及制备（2R，4'RS，8'RS）-α-生育酚的方法和 （全消旋） - α-生育酚通过新的中间产物。

公开(公告)号：US4120868A

公开(公告)日：1978-10-17

申请号：US859020

申请日：1977-12-09

申请人： Hagen Jaedicke ,  Joachim Paust

发明人： Hagen Jaedicke ,  Joachim Paust

IPC分类号： C07D319/06 ,  C07D319/04

CPC分类号： C07D319/06 ,  C07C403/14 ,  C07C2101/16

摘要： New acetals, containing a 6-membered ring, of 2-methyl-2,4-dialkoxy-3-buten-1-al, are obtained by reacting the corresponding 2-methyl-2-alkoxy-3-butyn-1-al-acetals with a mixture of the appropriate alcohol and an alkali metal alcoholate of the said alcohol at from 100.degree. to 200.degree. C. The acetals are intermediates for the preparation of carotinoid-based physiologically safe food dyes.

摘要翻译： 通过使相应的2-甲基-2-烷氧基-3-丁炔-1-基 - 丙酮与2-甲基-2,4-二烷氧基-3-丁烯-1-al的新的缩醛，含有6-元环的2-甲基-2,4-二烷氧基-3-丁烯-1- - 乙缩醛，其合适的醇和所述醇的碱金属醇化物的混合物在100至200℃下进行。缩醛是用于制备基于类胡萝卜素的生理安全食品染料的中间体。

公开(公告)号：US20050101669A1

公开(公告)日：2005-05-12

申请号：US10432455

申请日：2001-11-29

申请人： Martin Klatt ,  Markus Niebel ,  Joachim Paust

发明人： Martin Klatt ,  Markus Niebel ,  Joachim Paust

IPC分类号： C07D339/04 ,  A61K31/20

CPC分类号： C07D339/04

摘要： The present invention relates to a process for the preparation of R— and S-lipoic acid and R— and S-dihydrolipoic acid comprising (a) reaction of where MS is SO2—R′ and R and R′ independently of one another are C1-C6-alkyl, C3-C8-cycloalkyl, C3-C8-cycloalkylalkyl, aryl or aralkyl, with sodium sulfide and sulfur in methanol. The invention especially relates to processes for preparing pure R— or S-dihydrolipoic acid, which is either used directly or processed further to give R— and S-lipoic acid. The process also serves for the production of pharmaceuticals. The present invention further relates to a solution of sodium sulfide trihydrate and sulfur in methanol, the sulfur being present in a molar excess over the sodium sulfide trihydrate, and a kit which comprises the solution according to the invention.

摘要翻译： 本发明涉及制备R-和S-硫辛酸和R-和S-二氢硫辛酸的方法，其包括（a）其中MS为SO 2 -R'和R和 R'彼此独立地是C 1 -C 6 - 烷基，C 3 -C 8 - 环烷基 C 3 -C 8 - 环烷基烷基，芳基或芳烷基，与硫化钠和硫在甲醇中反应。 本发明特别涉及制备纯R-或S-二氢硫辛酸的方法，其可直接使用或进一步加工得到R-和S-硫辛酸。 该方法还用于生产药物。 本发明还涉及硫化钠三水合物和硫在甲醇中的溶液，所述硫以超过硫化钠三水合物的摩尔量存在，以及包含根据本发明的溶液的试剂盒。

公开(公告)号：US06348593B1

公开(公告)日：2002-02-19

申请号：US09497151

申请日：2000-02-03

申请人： Jörg Botzem ,  Hagen Jaedicke ,  Michael John ,  Joachim Paust

发明人： Jörg Botzem ,  Hagen Jaedicke ,  Michael John ,  Joachim Paust

IPC分类号： C07D47500

CPC分类号： C07C237/36 ,  C07C49/175 ,  C07C251/08 ,  C07D475/04

摘要： A process for preparing folic acid, which comprises reacting a tetraalkoxypropanol of the general formula I, in which the substituents R are C1-C4-alkyl, with triaminopyrimidone of the formula II and p-aminobenzoyl-L-glutamic acid of the formula III

摘要翻译： 一种制备叶酸的方法，其包括将取代基R为C1-C4烷基的通式I的四烷氧基丙醇与式II的三氨基吡啶酮和式III的对氨基苯甲酰基-L-谷氨酸反应