Zur Synthese sulfonierter Derivate von 2-Fluoranilin

Syntheses of Sulfonated Derivatives of 2-Fluoroaniline Synthesis of 4-amino-3-fluorobenzenesulfonic acid ( 3 ) was achieved in two ways: reaction of 2-fluoroaniline ( 1 ) with amidosulfonic acid and by first conventionally converting 4-nitro-3-fluoroaniline ( 8 ) to 4-nitro-3-fluorobenzenesulfonyl chloride ( 9 ) followed subsequently by hydrolysis to 3-fluoro-4-nitrobenzenesulfonic acid ( 10 ) and reduction. Hydrogenolysis of 3 gave sulfanilic acid ( 7 ). Both, sulfonation of fluorobenzene ( 6 ) to 4-fluorobenzenesulfonic acid ( 11 ) followed by nitration and sulfonation of 1-fluoro-2-nitrobenzene ( 12 ) led to 4-fluoro-3-nitrobenzenesulfonic acid ( 13 ). Reduction of 13 gave the isomeric 3-amino-4-fluorobenzenesulfonic acid ( 4 ), which was also obtained both by sulfonation of 1 and by sulfonation of o-fluoroacetanilide ( 14 ) followed by hydrolysis. Selective hydrogenolyses of 2-amino-5-bromo-3-fluorobenzenesulfonic acid ( 15 ), prepared by reaction of 4-bromo-2-fluoroaniline ( 16 ) with amidosulfonic acid, and of 4-amino-2-bromo-5-fluorobenzenesulfonic acid ( 20 ), obtained by sulfonation of 5-bromo-2-fluoroaniline ( 19 ) yielded the isomers 2-amino-3-fluorobenzenesulfonic acid ( 5 ) and 3 , respectively. The fourth isomer, 3-amino-2-fluorobenzenesulfonic acid ( 2 ), was synthesized by sulfur dioxide treatment of the diazonium chloride derived from 2-fluoro-3-nitroaniline ( 21 ) to 2-fluoro-3-nitrobenzenesulfonyl chloride ( 22 ), followed by hydrolysis to 2-fluoro-3-nitrobenzenesulfonic acid ( 23 ) and final Béchamp-reduction.     

Zur Synthese sulfonierter Derivate von 4-Fluoranilin

Syntheses of Sulfonated Derivatives of 4-Fluoroaniline Synthesis of 2-amino-5-fluorobenzenesulfonic acid ( 2 ) was achieved by baking the hydrogen sulfate of 4-fluoroaniline ( 1 ). Sulfonation of p-fluoroacetanilide ( 4 ) with oleum followed by hydrolysis gave 5-amino-2-fluorobenzenesulfonic acid ( 3 ). The same reaction with 1 yielded 3 in an impure state. The structures of 2 and 3 were confirmed by converting the diazonium chlorides derived from 5-fluoro-2-nitroaniline ( 5 ) and from 2-fluofo-5-nitroaniline ( 8 ) to 5-fluoro-2-nitrobenzene-sulfonyl chloride ( 6 ) and 2-fluoro-5-nitrobenzenesulfonyl chloride ( 9 ), respectively, followed by hydrolysis of 6 to 5-fluoro-2-nitrobenzenesulfonic acid ( 7 ), and of 9 to 2-fluoro-5-nitrobenzenesulfonic acid ( 10 ), and by final reduction. Compound 10 was also obtained by sulfonation of 1-fluoro-4-nitrobenzene ( 11 ) with oleum.     

Zur Synthese sulfonierter Derivate von 4- und 5-Aminoindan

On the Synthesis of Sulfonated Derivatives of 4- and 5-Aminoindan Baking the hydrogensulfate salt of 4-aminoindan (1) and 5-aminoindan (2) led, respectively, to 4-aminoindan-7-sulfonic acid (3) and 5-aminoindan-6-sulfonic acid (4). Acid 4 was also obtained by direct sulfonation of 2. 4-Aminoindan-6-sulfonic acid (5) and 6-aminoindan-4-sulfonic acid (6) were prepared by sulfonation of 4-nitroindan (7) and 5-nitroindan (9) , respectively, to 4-nitroindan-6-sulfonic acid (8) and 6-nitroindan-4-sulfonic acid (10) , followed by a Béchamp-reduction. Treatment of 1 with amidosulfuric acid gave 3 , whereas the same reaction with 2 led to a mixture of 4 and 5-aminoindan-4-sulfonic acid (11). Independent synthesis of 11 was achieved by the following sequence of reactions: sulfur dioxide treatment of the diazonium chloride derived from 4-amino-5-nitrodan (13) gave 5-nitroindan-4-sulfonyl chloride (14) ; hydrolysis to 5-nitroindan-4-sulfonic acid (15) , and final reduction. The 4-aminoindan-5-sulfonic acid (16) was synthesized by treatment of 4-amino-7-bromoindan (18) with amidosulfuric acid to give 4-amino-7-bromoindan-5-sulfonic acid (19) followed by hydrogenolysis. Sulfonation of 4-acetyl-amino-7-bromoindan (17) with oleum followed by hydrolysis led to 7-amino-4-bromoindan-5-sulfonic acid (20) , the structure of which was confirmed by reductive dehalogenation to 5 .     

Zur Synthese sulfonierter Derivate von 2,3-Dimethylanilin und 3,4-Dimethylanilin

On the Synthesis of Sulfonated Derivatives of 2,3-Dimethylaniline and 3,4-Dimethylaniline Baking the hydrogensulfate salt of 2,3-dimethylaniline ( 1 ) or of 3,4-dimethylaniline ( 2 ) led to 4-amino-2,3-dimethylbenzenesulfonic acid ( 4 ) and 2-amino-4,5-dimethylbenzenesulfonic acid ( 5 ), respectively (Scheme 1). The sulfonic acid 5 was also obtained by treatment of 2 with sulfuric acid or by reaction of 2 with amidosulfuric acid. 3-Amino-4,5-dimethylbenzenesulfonic acid ( 3 ) and 5-Amino-2,3-dimethylbenzenesulfonic acid ( 6 ) were prepared by sulfonation of 1,2-dimethyl-3-nitrobenzene ( 9 ) to 3,4-dimethyl-5-nitrobenzenesulfonic acid ( 11 ) and of 1,2-dimethyl-4-nitrobenzene ( 10 ) to 2,3-dimethyl-5-nitrobenzenesulfonic acid ( 12 ), respectively, with subsequent Béchamp reduction (Scheme 1). Preparations of 2-amino-3,4-dimethylbenzenesulfonic acid ( 7 ) and of 6-amino-2,3-dimethylbenzenesulfonic acid ( 8 ) were achieved by the sulfur dioxide treatment of the diazonium chlorides derived from 3,4-dimethyl-2-nitroaniline ( 24 ) and from 2,3-dimethyl-6-nitroaniline ( 31 ) to 3,4-dimethyl-2-nitrobenzenesulfonyl chloride ( 29 ) and 2,3-dimethyl-6-nitrobenzenesulfonyl chloride ( 32 ), respectively, followed by hydrolysis to 3,4-dimethyl-2-nitrobenzenesulfonic acid ( 30 ) and 2,3-dimethyl-6-nitrobenzenesulfonic acid ( 33 ), and final reduction (Scheme 3). Compound 7 was also synthesized by reaction of 4-chloro-2,3-dimethylaniline ( 23 ) with amidosulfuric acid to 2-amino-5-chloro-3,4-dimethylbenzenesulfonic acid ( 20 ) and subsequent hydrogenolysis (Scheme 2). 4′-Bromo-2′, 3′-dimethyl-acetanilide ( 13 ) and 4′-chloro-2′, 3′-dimethyl-acetanilide ( 14 ) on treatment with oleum yielded 5-acetylamino-2-bromo-3,4-dimethylbenzenesulfonic acid ( 17 ) and 5-acetylamino-2-chloro-3,4-dimethylbenzenesulfonic acid ( 18 ), respectively. Their structures were proven by hydrolysis to 5-amino-2-bromo-3,4-dimethylbenzenesulfonic acid ( 21 ) and 5-amino-2-chloro-3,4-dimethylbenzenesulfonic acid ( 22 ), followed by reductive dehalogenation to 3 .     

Zur Synthese sulfonierter Derivate von 4-Amino-1,3-dimethylbenzol und 2-Amino-1,3-dimethylbenzol

Syntheses of Sulfonated Derivatives of 4-Amino-1, 3-dimethylbenzene and 2-Amino-1, 3-dimethylbenzene Direct sulfonation of 4-amino-1, 3-dimethylbenzene (1) and sulfonation of 4-nitro-1,3-dimethylbenzene ( 4 ) to 4-nitro-1,3-dimethylbenzene-6-sulfonic acid ( 3 ) followed by reduction yield 4-amino-1,3-dimethylbenzene-6-sulfonic acid ( 2 ). The isomeric 5-sulfonic acid ( 5 ) however is prepared solely by baking the acid sulfate salt of 1 . Reaction of sulfur dioxide with the diazonium chloride derived from 2-amino-4-nitro-1,3-dimethylbenzene ( 7 ) leads to 4-nitro-1,3-dimethylbenzene-2-sulfonyl chloride ( 8 ), which is successively hydrolyzed to 4-nitro-1,3-dimethylbenzene-2-sulfonic acid ( 9 ) and reduced to 4-amino-1, 3-dimethylbenzene-2-sulfonic acid ( 6 ). Treatment of 4-amino-6-bromo-1,3-dimethylbenzene ( 12 ) and 4-amino-6-chloro-1, 3-dimethylbenzene ( 13 ), the former obtained by reduction of 4-chloro-6-nitro-1,3-dimethyl-benzene ( 10 ) and the latter from 4-chloro-6-nitro-1, 3-dimethylbenzene ( 11 ), with oleum yield 4-amino-6-bromo-1,3-dimethylbenzene-2-sulfonic acid ( 14 ) and 4-amino-6-chloro-1,3-dimethylbenzene-2-sulfonic acid ( 15 ) respectively; subsequent carbon-halogen hydrogenolyses of 14 and 15 lead also to 6 (Scheme 1). Baking the acid sulfate salt of 2-amino-1, 3-dimethylbenzene ( 17 ) gives 2-amino-1, 3-dimethylbenzene-5-sulfonic acid ( 16 ), whereas the isomeric 4-sulfonic acid ( 18 ) can be prepared by either of the following three possible pathways: Sulfonation of 2-nitro-1,3-dimethylbenzene ( 20 ) to 2-nitro-1,3-dimethylbenzene-4-sulfonic acid ( 21 ) followed by reduction or sulfonation of 2-acetylamino-1,3-dimethylbenzene ( 19 ) to 2-acetylamino-1,3-dimethylbenzene-4-sulfonic acid ( 22 ) with subsequent hydrolysis or direct sulfonation of 17 . Further sulfonation of 18 yields 2-amino 1,3-dimethylbenzene-4,6-disulfonic acid ( 23 ), the structure of which is independently confirmed by reduction of unequivocally prepared 2-nitro- 1,:3-dimethylbenzene-4,6-disulfonic acid ( 24 )(Scheme 2).     

Notizen zur Synthese sulfonierter Derivate von 5,6,7,8-Tetrahydro-1-naphthylamin und 5,6,7,8-Tetrahydro-2-naphthylamin

Notes on the Synthesis of Sulfonated Derivatives of 5,6,7,8-Tetrahydro-1-naphthylamine and 5,6,7,8-Tetrahydro-2-naphthylamine Sulfonation of 5,6,7,8-tetrahydro-1-naphthylamine ( 1 ) with sulfuric acid gave a mixture of 1-amino-5,6,7,8-tetrahydronaphthalene-2-sulfonic acid ( 2 ), 4-amino-5,6,7,8-tetrahydronaphthalene-2-sulfonic acid ( 13 ) and 4-amino-5,6,7,8-tetrahydronaphthalene-1-sulfonic acid ( 3 ). The same reaction with 5,6,7,8-tetrahydro-2-naphthylamine ( 20 ) yielded 3-amino-5,6,7,8-tetrahydronaphthalene-2-sulfonic acid ( 21 ); formation of 2-amino-5,6,7,8-tetrahydronaphthalene-1-sulfonic acid ( 16 ) or of 3-amino-5,6,7,8-tetrahydronaphthalene-1-sulfonic acid ( 24 ) was not observed. Treatment of 4-bromo-5,6,7,8-tetrahydro-1-naphthylamine ( 4 ) or of its 4-chloro analogue 5 with amidosulfuric acid gave 1-amino-4-bromo-5,6,7,8-tetrahydronaphthalene-2-sulfonic acid ( 9 ) and its 4-chloro analogue 10 , respectively, which were dehalogenated to 2 . Preparations of 13 and 24 were achieved by sulfonation of 5-nitro-1,2,3,4-tetrahydronaphthalene ( 14 ) and 6-nitro-1,2,3,4-tetrahydronaphthalene ( 22 ) to 4-nitro-5,6,7,8-tetrahydronaphthalene-2-sulfonic acid ( 15 ) and 3-nitro-5,6,7,8-tetrahydronaphthalene-1-sulfonic acid ( 23 ), respectively, followed by Béchamp reductions. The sulfonic acid 13 was also obtained by hydrogenolysis of 4-amino-1-bromo-5,6,7,8-tetrahydronaphthalene-2-sulfonic acid ( 11 ) or of its 1-chloro analogue 12 ; compounds 11 and 12 were synthesized from N-(4-bromo-5,6,7,8-tetrahydro-1-naphthyl)acetamide ( 7 ) and from its 4-chloro analogue 8 , respectively, by sulfonation with oleum and subsequent hydrolysis. By ‘baking’ the hydrogensulfate salt of 1 or 20 compounds 3 and 21 were obtained, respectively. Synthesis of 16 was achieved by sulfur dioxide treatment of the diazonium chloride derived from 2-nitro-5,6,7,8-tetrahydro-1-naphthylamine ( 17 ) giving 2-nitro-5,6,7,8-tetrahydronaphthalene-1-sulfonyl chloride ( 18 ), followed by hydrolysis of 18 to the corresponding sulfonic acid 19 and final reduction.     

Zur Synthese von Aminocaprolactam

α-Amino-?-caprolactam (I), an intermediate for the synthesis of L-lysine, has been synthesized by BECKMANN -rearrangement of α-amino-cyclohexanoneoxime (XII) in concentrated sulfuric acid (13% yield) or oleum (34% yield). Cyclisation of α-amino-?-bromocaproamide hydrobromide (VIII) did not yield I but an isomer of I of unknown structure (compound X). Upon hydrolysis X gave a compound XI which was similar to lysine in its chromatographic and electrophoretic behavior.     

Zur Synthese von Human-Big-Gastrin I

The synthesis of the tetratriacontapeptide amide corresponding to the revised primary structure of human big gastrin I is described. For this purpose the fragments were designed in view of the maximum use of those utilized in our previous synthesis of human big gastrin I according to the first sequence proposal. Consequently the key tripeptide-Pro-Pro-His- (sequence 7–9) was prepared in suitably protected form to be used as amino or carboxyl component for assembly of the segments 1–9 and 1–14, respectively. Final condensation of the latter nona- and tetradecapeptide derivatives with the C-terminal segments 10–34 and 15–34 via the azide and the dicyclohexylcarbodiimide/N-hydroxysuccinimide procedure, respectively, leads to crude fully protected human big gastrin I. Upon deprotection by exposure to trifluoroacetic acid in presence of ethanedithiol-(1,2) as scavanger, ion exchange chromatography and partition chromatography, the desired tetratriacontapeptide amide was isolated in satisfactory yield with a high degree of purity. The identical immunological behaviour of the synthetic material, if compared with that of natural human big gastrin I, represents ulterior strong evidence for the correctness of the newly proposed structure for this putative prohormonal form of the gastrins.

Kurzmitteilung:Wünsch E., Wendlberger G., Mladenova-Orlinova L., Göhring W., Jaeger E., Scharf R., Gregory R. A., Dockray G. J., Hoppe-Seyler's Z. Physiol. Chem.362, 179 (1981).     

Zur Synthese von substituierten Spirochromanen

Zusammenfassung -Salicyliden-lävulinsäure (I) reagiert mit Ketonen bei Einwirkung von Chlorwasserstoff nach der Art einerMichael-Addition zu Addukten, die durch einen zweimaligen Ringschluß substituierte Spirochromane als Endprodukte liefern (V).

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TheMichael reaction of -salicyliden-levulinic acid (I) with ketones under the catalytic influence of hydrogen chloride yields adducts, from which by two ring closures spirochromanes (V) are finally obtained.

     

Zur Synthese von β-Isosantalol

The synthesis of a new allylic alcohol with a norbornane skeleton is described. The convergent synthesis leads from 3-methylene-norbornan-2-one to -isosantalol (6). An important structural parameter of6 is derived from -Santalol (1), the main constituent of east indian sandalwoodoil with a powerful woody fragrance. Another structural parameter of6 is derived from isosantalol (3) with a weak woody odour. The odour of the new alcohol6 is weaker than that of3, probably because of too much osmophoric groups and a very reactivecis-1,3-butadiene-system. Another possible route to6 by means of aWittig-reaction did not succed.

Teil der Diplomarbeit vonM. Wiedenhorn, Universität Wien, 1980.     

Zur Synthese von isocamphananalogem Ephedrin

The synthesis of two new bicyclic phenylethylamine derivatives with potentially simpathomimetic effects is described. The synthesis of the isocamphane analogous apoephedrine (4) starts from the bicyclic methylketone5 and leads via its -bromoderivative6 and the corresponding tosylamidoketone8 to4. The synthesis of the title compound2 has been accomplished by preparing the -oximinoketone19 from the bicyclic ethylketone15 with subsequent reduction to the amino alcohol derivative20 and final selective monomethylation by theJohnstone procedure via the corresponding trifluoroacetamide.

Herrn Prof. Dr.K. Kratzl mit den besten Wünschen zum 70. Geburtstag gewidmet.     

Zur Synthese von Isocamphenilansäurederivaten

Improved procedures for the preparation of derivatives of the title compound are described.

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Als 1. Mitt. ist gedacht:G. Buchbauer, G. W. Hana undH. Koch, Mh. Chem.107, 387 (1976).     

Zur Synthese von Isocamphenilans?urederivaten

Improved procedures for the preparation of derivatives of the title compound are described.     

Zur Mikrobe Stimmung von Hydrazin und einigen seiner Derivate

Ohne Zusammenfassung     

Zur Synthese von Homocamphenilansäure

Syntheses of the title compound and of some of its derivatives are described. Homocamphenilanic acid could not be obtained by aDiels-Alder reaction of cyclohexadiene with an appropriate dienophile but is easily accessible via homocamphene by hydroboration of this homoterpene and subsequent oxidation of the reaction product.

Anmerkung: Zur Verwendung der Vorsilbe Homo- im Zusammenhang mit Norbornanen siehe Lit. [13] und Fußnote in Lit. [12].     

Zur Synthese von Cyclopentan-2-on-carbonsäureäthylester

Zusammenfassung Es wird eine mit Natriumäthylat in homogener Phase verlaufende intramolekulare Cyclisierung von Adipinsäureester zu Cyclopentan-2-on-carbonsäureester beschrieben.Die Reaktion verläuft inDMSO bzw.DMF als Lösungsmittel in ausgezeichneten Ausbeuten.