公开(公告)号：US4307037A

公开(公告)日：1981-12-22

申请号：US198262

申请日：1980-10-17

Applicant: Helmut Suchsland ,  Volker Hafner ,  Axel Kleemann

Inventor： Helmut Suchsland ,  Volker Hafner ,  Axel Kleemann

IPC: C07C253/08 ,  C07C20060101 ,  C07C67/00 ,  C07C253/00 ,  C07C255/24 ,  C07C255/61 ,  C07C120/00 ,  C07C121/43

CPC classification number: C07C255/00

Abstract: The invention is directed to a process for the production of iminodiacetonitrile by reaction of hexamethylenetetramine with hydrogen cyanide in acidic aqueous mediums. In this process the pH during the reaction which is 5.5 to 7.5 at the beginning is progressively lowered, altogether around 0.5 to 3.5 units and free formaldehyde is present only to a slight extent. Through this and in contrast to the known processes the formation of byproducts is suppressed and iminodiacetonitrile is produced directly in very good yields and sufficiently pure for further use.

Abstract translation: 本发明涉及通过在酸性水性介质中六亚甲基四胺与氰化氢的反应制备亚氨基二乙腈的方法。 在此过程中，开始时5.5至7.5的反应中的pH逐渐降低，共约0.5-3.5个单位，游离甲醛仅在一定程度上存在。 通过这一点，与已知的方法相反，副产物的形成被抑制，亚氨基乙腈直接以非常好的产率直接生产，并且足够纯以供进一步使用。

公开(公告)号：US4263308A

公开(公告)日：1981-04-21

申请号：US112100

申请日：1980-01-14

Applicant: Jurgen Engel ,  Axel Kleemann ,  Ute-Achterrath Tuckermann ,  Klaus Thiemer

Inventor： Jurgen Engel ,  Axel Kleemann ,  Ute-Achterrath Tuckermann ,  Klaus Thiemer

IPC: C07D409/14 ,  A61K31/4433 ,  A61K31/445 ,  C07D333/00 ,  C07D417/14

CPC classification number: C07D333/00

Abstract: There are prepared compounds of the formula ##STR1## where R.sub.1 is hydrogen or hydroxy, R.sub.2 is hydrogen or R.sub.1 and R.sub.2 together represent a second bond between the carbon atoms carrying R.sub.1 and R.sub.2, Alk is a C.sub.2 -C.sub.6 alkylene group, R.sub.3 is a C.sub.3 -C.sub.8 -cycloalkyl group, a C.sub.1 -C.sub.6 -alkyl group, a C.sub.1 -C.sub.6 -hydroxyalkyl group or a C.sub.2 -C.sub.6 -hydroxyalkoxy-C.sub.1 -C.sub.6 -alkyl group and the groups R.sub.4, R.sub.5, R.sub.6 and R.sub.7 are the same or different and are hydrogen, C.sub.1 -C.sub.6 -alkyl group or halogen atoms, their N-oxides, their quaternary salts and their acid addition salts. There are also described processes for their production. The compounds have a strong bronchospasmolytic activity, antianaphylactic activity and an antihistamine-antiserotonine activity.

Abstract translation: 制备式为“IMAGE”的化合物，其中R 1为氢或羟基，R 2为氢或R 1和R 2一起代表携带R1和R2的碳原子之间的第二个键，Alk为C2-C6亚烷基，R3为 C 3 -C 8 - 环烷基，C 1 -C 6烷基，C 1 -C 6羟基烷基或C 2 -C 6羟基烷氧基-C 1 -C 6 - 烷基，R 4，R 5，R 6和R 7基团相同或 不同的是氢，C 1 -C 6烷基或卤原子，它们的N-氧化物，它们的季盐和它们的酸加成盐。 还描述了其生产方法。 该化合物具有强的支气管痉挛分解活性，抗过敏活性和抗组织胺 - 抗血清素活性。

公开(公告)号：US4254269A

公开(公告)日：1981-03-03

申请号：US56838

申请日：1979-07-12

Applicant: Axel Kleemann ,  Ingomar Nubert ,  Fritz Stroman ,  Klaus Thiemer

Inventor： Axel Kleemann ,  Ingomar Nubert ,  Fritz Stroman ,  Klaus Thiemer

IPC: C07D333/24 ,  A61K31/38 ,  A61K31/381 ,  A61P9/08 ,  C07D333/16 ,  C07D333/20 ,  C07D333/12

CPC classification number: C07D333/20 ,  C07D333/16

Abstract: There are prepared compounds of the formula ##STR1## where >A--B-- has either the structure >C(OH)--CH.sub.2 -- or the structure >C.dbd.CH, Alk is a straight or branched chain C.sub.1 -C.sub.5 -alkylene group and Y is a C.sub.3 -C.sub.7 -cycloalkyl group, a benzyl group, a methylenedioxybenzyl group, a benzyl group having one, two or three C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -alkoxy group substituents, a C.sub.1 -C.sub.6 -alkyl group, or a C.sub.1 -C.sub.6 -alkyl group substituted by an amino group, a di C.sub.1 -C.sub.4 -alkylamino group, a mono C.sub.1 -C.sub.4 -alkyl-amino group, a morpholino group, a piperazino group or a 4-(C.sub.1 -C.sub.4 -alkyl)-piperazino group, or Y is ##STR2## where R is hydrogen or a C.sub.1 -C.sub.4 -alkyl group and T is hydrogen or a C.sub.2 -C.sub.6 -alkanoyl group or where --NHY is ##STR3## where R' is hydrogen, phenyl, phenyl substituted once or twice by C.sub.1 -C.sub.4 -alkyl groups, a C.sub.1 -C.sub.4 -alkoxy group or by halogen atoms, a C.sub.1 -C.sub.6 -alkyl group, a C.sub.1 -C.sub.4 -hydroxyalkyl group or a phenalkyl group whose alkyl portion consists of 1-4 carbon atoms or such a phenalkyl group containing 1 to 3 C.sub.1 -C.sub.4 -alkoxy group substituents or when Alk has 2 to 5 carbon atoms the group --NHY is a di-C.sub.1 -C.sub.4 -alkylamino group or the group --NH--CH(R)--CH(OH)--C.sub.6 H.sub.5 and salts thereof. The compounds are effective in improving peripheral and cerebral circulation. There are also produced intermediate compounds of formula (II) where NHY is replaced by chlorine, bromine or iodine.

Abstract translation: 制备式（Ⅰ）化合物，其中AB-具有> C（OH）-CH 2 - 或结构> C = CH的结构，Alk是直链或支链C 1 -C 5亚烷基 Y为C 3 -C 7 - 环烷基，苄基，亚甲二氧基苄基，具有一个，两个或三个C 1 -C 4 - 烷基或C 1 -C 4 - 烷氧基取代基的苄基，C 1 -C 6烷基， 或被氨基取代的C1-C6-烷基，二C1-C4-烷基氨基，单C1-C4-烷基 - 氨基，吗啉代基，哌嗪基或4-（C1-C4- 烷基） - 哌嗪基，或Y是其中R是氢或C 1 -C 4 - 烷基，T是氢或C 2 -C 6烷酰基或其中R'是氢的-NHY是“ 苯基，被C 1 -C 4 - 烷基取代一次或两次的苯基，C 1 -C 4 - 烷氧基或卤素原子，C 1 -C 6 - 烷基，C 1 -C 4 - 羟基烷基或烷基部分由 1-4个碳原子的烷基或含1-3个C 1 -C 4 - 烷氧基的苯烷基 基团取代基，或当Alk具有2至5个碳原子时，基团-NHY是二-C 1 - C 4 - 烷基氨基或基团-NH-CH（R）-CH（OH）-C 6 H 5及其盐。 该化合物有效改善周围和脑部循环。 还制备式（II）的中间体化合物，其中NHY被氯，溴或碘代替。

公开(公告)号：US4224226A

公开(公告)日：1980-09-23

申请号：US926322

申请日：1978-07-20

Applicant: Axel Kleemann ,  Herbert Klenk ,  Heribert Offermanns ,  Paul Scherberich ,  Werner Schwarze

Inventor： Axel Kleemann ,  Herbert Klenk ,  Heribert Offermanns ,  Paul Scherberich ,  Werner Schwarze

IPC: A01N25/00 ,  A01P3/00 ,  A01P13/00 ,  C07C67/00 ,  C07C231/00 ,  C07C231/06 ,  C07C231/08 ,  C07C235/72 ,  C07D307/54 ,  C07C102/08

CPC classification number: C07D307/54

Abstract: Compounds are prepared of the formula ##STR1## where R' is a t-alkyl group having 4 to 18 carbon atoms, preferably t-butyl, t-amyl or t-octyl and R is a straight or branched chain alkyl group with 1 to 18 carbon atoms, preferably 1 to 10 carbon atoms or an alkyl group substituted with one or more phenyl groups or a halogen atom, particularly a chlorine atom, or a cycloalkyl group with 3 to 8 carbon atoms, particularly cyclopropyl, which can be substituted by one or more 1 to 3 carbon atom alkyl groups or one or more halogen atoms, preferably chlorine, or phenyl or naphthyl or a five membered heterocyclic group or such phenyl, naphthyl or heterocyclic group substituted by halogen atoms, nitro groups, alkyl or alkoxy with 1 to 5 carbon atoms by condensing in acid medium an acyl cyanide of the formulaR--CO--CN (II)where R is as defined above with either(a) a tertiary alcohol of the formulaHO--R' (III) in which R' is as defined above, or preferably(b) an alkene of the formula ##STR2## where R.sub.1 and R.sub.2 are the same or different and are hydrogen or an alkyl group and wherein R.sub.3 and R.sub.4 are the same or different and wherein the alkyl groups in each case can be 1 to 15 carbon atoms. Some of the compounds are new. They are useful as intermediates for synthesizing herbicides and can be used directly as fungicides.

Abstract translation: 化合物由式（I）制备，其中R'是具有4至18个碳原子的叔烷基，优选叔丁基，叔戊基或叔辛基，R是直链或支链烷基 具有1至18个碳原子，优选1至10个碳原子的烷基或被一个或多个苯基或卤素原子，特别是氯原子或具有3至8个碳原子的环烷基，特别是环丙基取代的烷基，其可以 被一个或多个1至3个碳原子的烷基或一个或多个卤素原子，优选氯，或苯基或萘基或五元杂环基或被卤素原子取代的苯基，萘基或杂环基，硝基，烷基 或具有1至5个碳原子的烷氧基，通过在酸性介质中缩合式R-CO-CN（II）的酰基氰，其中R如上定义，与（a）式HO-R'（III ），其中R'如上所定义，或优选（b）式“IMAGE”（ IV）其中R 1和R 2相同或不同并且是氢或烷基，并且其中R 3和R 4相同或不同，并且其中每种情况下的烷基可以是1至15个碳原子。 一些化合物是新的。 它们可用作合成除草剂的中间体，可直接用作杀真菌剂。

公开(公告)号：US4222956A

公开(公告)日：1980-09-16

申请号：US12133

申请日：1979-02-14

Applicant: Axel Kleemann ,  Peter Schalke ,  Detlef Arnoldi

Inventor： Axel Kleemann ,  Peter Schalke ,  Detlef Arnoldi

IPC: C07C255/19 ,  C07C20060101 ,  C07C67/00 ,  C07C253/00 ,  C07C120/00 ,  C07C121/407

CPC classification number: C07C255/00

Abstract: Cyanocarboxylic acids are prepared by reacting halocarboxylic acids with cyanohydrins, preferably at a pH of 9 to 11.

Abstract translation: 氰基羧酸通过卤代羧酸与氰醇反应制备，优选在9至11的pH下进行。

公开(公告)号：US4175088A

公开(公告)日：1979-11-20

申请号：US867294

申请日：1978-01-05

Applicant: Axel Kleemann ,  Reinhold Kiel ,  Ingomar Nubert

Inventor： Axel Kleemann ,  Reinhold Kiel ,  Ingomar Nubert

IPC: C07D333/14 ,  A61K31/382 ,  C07D333/16 ,  C07D333/20

CPC classification number: C07D333/16 ,  C07D333/20

Abstract: [1,1-dithien-(3)-yl-1-hydroxy-(3)-propyl]-[1-phenyl-1-hydroxy-(2)-propyl]-amine is prepared by condensing thien-(3)-yl lithium with a .beta.-halogen propionic acid alkyl ester of the formula ##STR1## where R is a lower alkyl group and Hal is chlorine, bromine or iodine, in an inert medium at a temperature below -50.degree. C. to form a compound of the formula ##STR2## which is then reacted with 2-amino-1-hydroxy-1-phenylpropane in an inert medium in the presence of a basic compound. The product cn be converted to [1,1-dithien-(3)-yl-(1)-propen-(3)-yl]-[1-phenyl-(2)-propyl]-amine by dehydration.

Abstract translation: 通过将噻吩（3） - （3） - （1） - 羟基 - （3） - 丙基] - [1-苯基-1-羟基 - （2） ） - 基锂与式（II）的β-卤代丙酸烷基酯反应，其中R是低级烷基，Hal是氯，溴或碘，在惰性介质中，温度低于-50℃ 形成式（III）的化合物，然后在碱性化合物的存在下，在惰性介质中与2-氨基-1-羟基-1-苯基丙烷反应。 通过脱水将产物转化为[1,1-二噻吩 - （3） - 基 - （1） - 丙烯 - （3） - 基] - [1-苯基 - （2） - 丙基] - 胺。

公开(公告)号：US5707933A

公开(公告)日：1998-01-13

申请号：US463279

申请日：1995-06-05

Applicant: Axel Kleemann ,  Robert John Griffith Searle

Inventor： Axel Kleemann ,  Robert John Griffith Searle

IPC: A01N43/56 ,  A01P13/00 ,  C07D401/12 ,  C07D401/02

CPC classification number: C07D401/12 ,  A01N43/56

Abstract: Herbicidal picolinamide derivatives are provided having the formula I ##STR1## which Z represents an oxygen or sulphur atom, R.sup.1 and R.sup.2 each independently represents a hydrogen atom or an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, alkaryl, hydroxy, alkoxy, alkenyloxy, alkynyloxy, alkylcarbonyl, amino, mono- or di-alkylamino, alkoxycarbonylamino, arylamino, arylalkylamino or dialkylcarbamoyl group, or together represent an alkylene chain which is optionally interrupted by an oxygen, or sulphur atom or by a group --NR-- in which R represents a hydrogen atom or an alkyl group, R.sup.3 independently represents a halogen atom or an alkyl or haloalkyl group, R.sup.4, R.sup.5 and R.sup.6 each independently represents a hydrogen or halogen atom, an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, alkaryl, alkoxy, amino, mono- or di-alkylamino, alkoxycarbonylamino, arylamino, dialkylcarbamoyl, acyl or acylamido group or a cyano group, with the proviso that R.sup.5 and R.sup.6 do not represent an acyl, acylamido or cyano group, and n represents 0, 1, 2 or 3.

Abstract translation: 提供除草的吡啶酰胺衍生物，其具有式I（I），其中Z表示氧或硫原子，R1和R2各自独立地表示氢原子或任选取代的烷基，烯基，炔基，环烷基，环烷基烷基，芳基，芳烷基 ，烷芳基，羟基，烷氧基，烯氧基，炔氧基，烷基羰基，氨基，单 - 或二 - 烷基氨基，烷氧基羰基氨基，芳基氨基，芳基烷基氨基或二烷基氨基甲酰基，或一起表示任选被氧或硫原子中断的亚烷基链， 基团-NR-，其中R表示氢原子或烷基，R3独立地表示卤素原子或烷基或卤代烷基，R4，R5和R6各自独立地表示氢或卤素原子，任选取代的烷基，烯基 ，炔基，环烷基，环烷基烷基，芳基，芳烷基，烷芳基，烷氧基，氨基，单 - 或二 - 烷基氨基，烷氧基羰基氨基，芳基氨基，二烷基氨基甲酰基，酰基或酰基酰氨基或ac yano基团，条件是R 5和R 6不表示酰基，酰氨基或氰基，n表示0,1,2或3。

公开(公告)号：US4966732A

公开(公告)日：1990-10-30

申请号：US73584

申请日：1987-07-15

Applicant: Guenes Giray ,  Klaus Huthmacher ,  Axel Kleemann ,  Thomas Lied

Inventor： Guenes Giray ,  Klaus Huthmacher ,  Axel Kleemann ,  Thomas Lied

IPC: C07C323/52 ,  A61K31/385 ,  A61P1/16 ,  A61P25/00 ,  C07C67/00 ,  C07C313/00 ,  C07C319/06 ,  C07C319/14 ,  C07C319/20 ,  C07C323/22 ,  C07C327/22 ,  C07D339/04

CPC classification number: C07D339/04 ,  C07C323/00

Abstract: 1,2-Dithiolane-3-pentanoic acid (D,L-thioctic acid) of the formula ##STR1## is prepared by a process comprising (a) reacting a 2-(3-alkylthiopropionyl)-cyclopentanone-1 of the formula ##STR2## where R is a C.sub.1 -C.sub.4 alkyl, phenyl or benzyl in aqueous alkaline solution at a temperature of about 20.degree. C. to about 90.degree. C. to form the corresponding carboxylic acid of formula VI ##STR3## (b) reacting the compound of formula VI with an alkyl mercaptan at a temperature between -20.degree. C. and 0.degree. C. to form the corresponding thioketal of formula VII ##STR4## (c) reacting the compound of formula VII with sodium in liquid ammonia at temperature temperture between -60.degree. C. and -10.degree. C. to form the 6,8-dimercaptooctanic acid of formual VIII ##STR5## (d) reacting the 6,8-dimercaptooctanoic acid of formula VIII in alkaline solution with an iron (III) salt and oxygen to form the 1,2-dithiolane-3-pentanoic acid of formula IX, or in place of steps (a) through (c) reacting an acid of formula XII ##STR6## where R.sub.1 and R.sub.2 are hydrogen, C.sub.1 -C.sub.4 -alkyl, phenyl or benzyl, with the proviso that both R.sub.1 and R.sub.2 cannot be benzyl, with sodium in liquid ammonia at a temperature between -60.degree. C. and -10.degree. C. to form the corresponding 6,8-dimercaptooctanoic acid of formula VIII. The compounds of formulae VI, VII, XII are new.

公开(公告)号：US4824987A

公开(公告)日：1989-04-25

申请号：US197343

申请日：1988-05-23

Applicant: Axel Kleemann ,  Herbert Klenk ,  Klaus Huthmacher ,  Dieter Most

Inventor： Axel Kleemann ,  Herbert Klenk ,  Klaus Huthmacher ,  Dieter Most

IPC: C07C253/04 ,  C07C255/32 ,  C07C255/33 ,  C07C255/35 ,  C07C120/00

CPC classification number: C07C255/00

Abstract: A method of preparing m-trifluoromethylphenyl acetonitrile of the formula ##STR1## in which m-trifluoromethyl toluene is reacted with cyanogen chloride in the gas phase at 600.degree. to 750.degree. C.

Abstract translation: 制备式“IMAGE”的间三氟甲基苯基乙腈的方法，其中间 - 三氟甲基甲苯与氯化氰在气相中在600至750℃下反应。

公开(公告)号：US4716242A

公开(公告)日：1987-12-29

申请号：US704465

申请日：1985-02-22

Applicant: Jurgen Engel ,  Axel Kleemann ,  Ulf Niemeyer ,  Peter Hilgard ,  Joerg Pohl

Inventor： Jurgen Engel ,  Axel Kleemann ,  Ulf Niemeyer ,  Peter Hilgard ,  Joerg Pohl

IPC: C07F9/24 ,  A61K31/675 ,  A61P35/00 ,  A61P35/02 ,  C07F9/22 ,  C07F9/6584 ,  C07F9/40

CPC classification number: C07F9/65846

Abstract: There are provided new antitumor salts of oxazaphosphorine derivatives of the formula ##STR1## where R.sub.1, R.sub.2, and R.sub.3 are the same or different and represent hydrogen, methyl, ethyl, 2-chloroethyl, or 2-methanesulfonyloxyethyl and wherein at least two of these residues are 2-chloroethyl and/or 2-methanesulfonyl-oxyethyl and A is the group --S--alk--SO.sub.3 H or --N(OH)--CONH--alk--CO.sub.2 H and alk represents a C.sub.2 -C.sub.6 -alkylene residue optionally containing a mercapto group, whereby alk also can be --CH.sub.2 -- in case there is a carboxy group attached to the alk group, with homocysteinethiolactone or .alpha.-amino-.epsilon.-caprolactam or a basic compound of the formula: ##STR2## wherein R.sub.4 is a hydroxy group, an amino group or a C.sub.1 -C.sub.6 -alkoxy group, R.sub.5 is hydrogen or a difluoromethyl group, R.sub.6 is hydrogen, an indolyl-(3)-methyl residue, imidazolyl-(4)-methyl residue, a C.sub.1 -C.sub.10 -alkyl group or a C.sub.1 -C.sub.10 -alkyl group which is substituted by a hydroxy group, a C.sub.1 -C.sub.6 -alkoxy group, a mercapto group, a C.sub.1 -C.sub.6 -alkylmercapto group, a phenyl group, a hydroxy phenyl group, an amino-C.sub.1 -C.sub.6 -alkylmercapto group, an amino-C.sub.1 -C.sub.6 -alkoxy group, an amino group, an aminocarbonyl group, a ureido group (H.sub.2 NCONH--), a guanidino group or a C.sub.1 -C.sub.6 -alkoxycarbonyl group, or wherein R.sub.6 together with the structured portion >CR.sub.5 (NR.sub.7 R.sub.8) forms the proline residue, the 4-hydroxy-proline residue or the 2-oxo-3-amino-3-difluoromethyl-piperidine and the residues R.sub.7 and R.sub.8 represent hydrogen or C.sub.1 -C.sub.6 -alkyl residues.

Abstract translation: 提供了新的式（ⅩⅧ）的恶唑烷磷衍生物的抗肿瘤盐，其中R 1，R 2和R 3相同或不同，代表氢，甲基，乙基，2-氯乙基或2-甲磺酰氧基乙基，其中这些 残基是2-氯乙基和/或2-甲磺酰氧基乙基，A是-S-烷基-SO 3 H或-N（OH）-CONH-烷基-CO 2 H，烷基代表任选含有巯基的C 2 -C 6亚烷基 其中烷基也可以是-CH 2 - ，如果存在与烷基连接的羧基，具有同半胱氨酸硫内酯或α-氨基 - ε-己内酰胺或下式的碱性化合物：其中R 4是羟基 基团，氨基或C1-C6-烷氧基，R5是氢或二氟甲基，R6是氢，吲哚基 - （3） - 甲基残基，咪唑基 - （4） - 甲基残基，C1-C10- 烷基或被羟基，C1-C6-烷氧基，巯基，C1-C6烷基巯基取代的C1-C10-烷基 基团，苯基，羟基苯基，氨基-C 1 -C 6烷基巯基，氨基-C 1 -C 6烷氧基，氨基，氨基羰基，脲基（H 2 NCONH-），胍基 或C 1 -C 6烷氧基羰基，或其中R 6与结构部分> CR 5（NR 7 R 8）一起形成脯氨酸残基，4-羟基 - 脯氨酸残基或2-氧代-3-氨基-3-二氟甲基 - 哌啶和 残基R7和R8表示氢或C1-C6烷基残基。