Degussa Aktiengesellschaft

Deutsche Gold- Und Silber-Scheideanstalt Vormals Roessler

Asta Pharma Aktiengesellschaft

Asta-Werke Aktiengesellschaft, Chemische Fabrik

Degussa Akteinsellschaft

Degussa Aktienbesellschaft

Axel Kleemann

Jurgen Martens

Karlheinz Drauz

Horst Weigel

Werner Schwarze

Herbert Klenk

Klaus Thiemer

Klaus Huthmacher

Jurgen Engel

Paul Scherberich

Horst Bethge

Fritz Stroman

Marc Samson

Michael Karrenbauer

Bernd Lehmann

Klaus Deller

Wolfgang Leuchtenberger

Peter M Schalke

Gerd Schreyer

Heinz Friedrich

Theodor Lussling

Rudolf M Wagner

Ingomar Nubert

Robert S Nygren

Heinz Kolb

Guenes Giray

Thomas Lied

Heribert Offermanns

Helmut Beschke

Gunther Prescher

Wolfgang Heim

Fritz Schafer

Harald Jakob

Istvan Szelenyi

Bernd Nickel

Guenter Prescher

Franz Effenberger

Peter Hilgard

Manfred Schmidt

Rolf Wirthwein

Klaus Posselt

Ulf Niemeyer

Volker Hafner

Elisabeth Wolf-Heuss

Vladimir Jakovlev

Dieter Most

Karl H Klingler

Hans Remmel

Johann Buchler

Helmut Suchsland

Gunes Giray

Wolf D Pfeifer

Rudi E Moerck

Wolfgang Hohn

Wolfgang Schulz

Ludwig-Karl Schworzer

Rudi Moerck

Elizabeth Wolf-Heuss

Kurt Klostermann

Reinhold Kiel

Erik Westermann

Joerg Pohl

Anne Rindfuss

Ansgar Von Schlichtegroll

Rolf Braun

Detlef Arnoldi

Ute-Achterrath Tuckermann

Bernd Lehamnn

Bergstein Wolfgang

Gregor Schuster

Wolfgang Bergstein

An improved method of preparing 1,6-di(N.sup.3 -cyano-N.sup.1 -guanidino) hexane from alkali dicyanamide and a hexamethylene diammonium salt in alcoholic solution or suspension. The reaction is carried out in the presence of a limited amount of water and of a catalytic amount of a base, preferably a tertiary amine. The pH of the reaction mixture at the start of the reaction is 8 to 10. After the reaction is over, the reaction mixture is compounded with water at a temperature above 80.degree. C. and the coarse product which crystallizes out is separated from the liquid phase. Preferably, sodium dicyanamide and hexamethylene diamine dihydrochloride, preferably formed in situ from aqueous 1,6-diaminohexane and aqueous hydrochloric acid, are reacted at pH 9-9.5 in n-butanol in the presence of 0.1 to 20% by wt. water in relation to the solvent including water. 1,6-di(N.sup.3 -cyano-N.sup.1 -guanidino) hexane is obtained in a high yield (85-86%) and with great purity (95-97%) and with a considerably improved space-time yield.

Method of preparing 1,6-di(N.sup.3 -cyano-N.sup.1 -guanidino) hexane

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.

Process for the production of 1,2-dithiolan-3-pentanoic acid (thioctic

Compounds of formula ##STR1## wherein the radicals R.sub.1 and R.sub.2 are the same or different and represent hydrogen, halogen atoms, a trifluoromethyl group, a cyano, a nitro group, an amino group, a mono-C.sub.1 -C.sub.6 -alkylamino group, a di-C.sub.1 -C.sub.6 -alkylamino group, an amino group that is substituted by a phenyl C.sub.1 -C.sub.4 -alkyl radical, a C.sub.2 -C.sub.6 -alkanoyl-amino group, a C.sub.1 -C.sub.6 -alkoxycarbonyl amino group, a C.sub.1 -C.sub.6 -alkyl group optionally substituted by a phenyl radical, a hydroxy group, a C.sub.1 -C.sub.6 -alkoxy group, a C.sub.2 -C.sub.6 -alkanoyloxy group, a phenoxy group or represent a carbamoyl group optionally substituted by one or two C.sub.1 -C.sub.6 -alkyl groups and the radical A is an acyl group which is derived from an amino acid as well as processes for their preparation.

Nitrogen-containing cyclo-aliphatic compounds having an amino radical

The invention relates to the preparation of optically active salts of the general formula ##STR1## from which the corresponding optically active 3-chloro-2-hydroxypropyltrimethyl ammonium chloride can be obtained by treatment with mineral acid. The L(-) form of this compound is a valuable component for the synthesis of L(-) carnitine.

Optically active salts of a substituted thiazolidine-4-carboxylate and

A method for the catalytic epoxidation of olefines with hydrogen peroxide in the presence of tungsten oxo complexes or of a binuclear compound of the type .mu.-oxobis [porphyrinato-oxo tungsten (V)] or cis-oxo peroxo tungsten (VI) prophyrin or cis-dioxo porphyrinatotungsten (VI) with octaethyl porphyrin or 5,10,15,20-tetraphenyl porphyrin or 5,10,15,20-tetra(4-pyridyl)-porphyrin as ligands.

Method for the catalytic epoxidation of olefins with hydrogen peroxide

L-amino acids present in cleavage solutions obtained in the acylase-catalyzed cleavage of N-acetyl-D,L-amino acids are isolated by use of a strongly acidic ion exchanger in H+ form. First, the mother liquor from a previous treatment cycle is fed to the ion exchanger, and then the cleavage solution and finally the wash water and the discharge from the ion exchanger which is pH-controlled is analyzed into an 'effluent water fraction', an 'N-acetyl-D-amino acid fraction' and an 'L-amino acid fraction'. The last fraction is adjusted by addition of fresh cleavage solution to a pH of between 4.0 and 6.0, and from the mixture which is thus obtained the L-amino acid is isolated by crystallization. The mother liquor which is obtained is recycled back into a subsequent treatment cycle.

Process for the isolation of L-amino acids

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.

Method of preparing m-trifluoromethylphenyl acetonitrile

Compounds of forumla XII ##STR1## wherein R.sub.1 is hydrogen and R.sub.2 is phenyl or benzyl are useful as intermediates in the preparation of 1,2-dithiolane-3-pentanoic acid (D,L-thioctic acid) of formula IX ##STR2##

Intermediates for the production of 1,2-dithiolan acid (thioctic acid)

The reaction mixture obtained in the enzymatic reaction of fumaric acid to form L-malic acid contains the L-malic acid and unreacted fumaric acid as their salts. To recover pure solutions of L-malic acid the reaction mixture is treated at 50.degree. to 150.degree. C. with cation exchangers. The eluate after concentration to 30 to 80 weight % content of L-malic acid is filtered. The pure L-malic acid is recovered by evaporating the solutions, in a given case after treatment with activated carbon.

Process for the recovery of malic acid

The production of solutions of hydrogen peroxide in phenol or its derivatives, e.g. hydrocarbyl substituted phenols, halo substituted phenols or phenol ethers, is carried out in a single step. Practically no loss of hydrogen peroxide occurs since a total distillation of hydrogen peroxide together with phenol or phenol derivative is avoided. Simultaneously the solutions obtained are practically free from water. The mixture of phenol or phenol derivative and aqueous hydrogen peroxide is treated with a material that boils below the boiling point of hydrogen peroxide, phenol or phenol derivative or forms an azeotrope with water that boils below the boiling point of hydrogen peroxide, phenol or phenol derivative and the water removed as an azeotrope. The solution of hydrogen peroxide in phenol or phenol derivative which remains behind is suitable for carrying out oxidation reactions and above all, also for hydroxylation reactions. The latter as especially advantageously carried out in the presence of sulfur-, selenium-, or tellurium oxide.

Process for the production of non-aqueous hydrogen peroxide solutions

There is disclosed a process for the production of 1,4-bis-[3-(3,4,5-trimethoxybenzyloxy)-propyl]-diazepane which consists of first reacting 3-aminopropanol with acrylonitrile and subsequently reacting in aqueous solution with formaldehyde and hydrocyanic acid or with formaldehyde and an alkali cyanide in the presence of alkali hydrogen sulfite to form cyanomethyl-(2-cyano-ethyl)-(3-hydroxy-propyl)-amine; hydrogenating the thus obtained reaction product in the presence of a hydrogenating catalyst and ammonia to 1 (3-hydroxy-propyl)-1,4-diazepane and reacting the latter compound for example with 3-halogen propanol or with allyl alcohol and introducing two 3,4,5-trimethoxy-benzoyl groups into the thus obtained reaction product by esterification.

Production of 1-(3-hydroxy-propyl)-1,4-diazepane and

3-oxonitriles are produced by reaction of carboxylic acid esters with carboxylic acid nitriles in the presence of 70 to 80% suspension of sodium hydride in white oil. The oxonitrile are intermediate products for the production of 3-oxocarboxylic acid amides or esters and pesticides.

Process for the production of 3-oxonitriles

To produce thiosemicarbazide hydrazine is reacted with hydrogen cyanide and sulfur to form hydrazine thiocyanate, and this is then converted into the thiosemicarbazide at an elevated temperature. Advantageously, the reaction is carried out in a polar solvent.

Process for the production of thiosemicarbazide

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 &gt;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.

Salts of oxazaphosphorine derivatives

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Hanau, Germany

Axel Kleemann