Patented Dec. 26, 1950 2,535,417

UNlTED stares mm orrics 2,535,417 PROCESS FOR THE liIBRDDUCTION OF LIU-PHENAN’EHRULINE Ernst Hodel, Birstelden. near Basel, and Hans Gysin, Basel. Switzerland. assignors to J. R. Geigy A. G., Basel, Switzerland, a Swiss ?rm Ne Drawing. Application :February 27, 1950. Se rial No. 145,628. In Switzerland March 4, 1949' 5 Glaims. (Cl: 26ii—288) 1. 2 1.10-phenanthroline was ?rst produced by Blau copper chloride, and the 1.10-phenanthroline '(Monatshefte 19, 64f‘, 1898) by condensing ‘isolated in the form of its copper complex com O-phenyIene diamine withv 2 mols of glycerine ‘pound. It can be liberated from the complex by means of‘ sulphuric acid in the presence of compound with hydrogen sulphide by methods nitrobenzene, also by condensing S-aminoquino known per se and puri?ed by distillation or line with 1 moi of glycerine under the same recrystallisation, for example, in water. reaction conditions. As S-aminoquinoline is In this way, by the use of nitrobenzene sul obtained from o-nitraniline by condensat‘on with ‘phonic acid as dehydrogenating agent, a yield glycerine and reduction, both processes can be ‘of more than 30% of the theoretical calculated called one and three step processes. Blau also ‘on o~phenylenediamine and one of about 25% by describes a number oi metal complex compounds the use of arsenic acid can be obtained. A yield of 1.10-phenanthmline. The iron-phenan of 69% is obtained when 8-aminoquinoline is throline complex is later suggested as reversible used as starting product. Redox indicator, the ferrous step is brilliant red This is a three or fourfold increase over the coloured‘. the ferric step is blue. (Walden. Ham previors one step process and also over- the three mett and Chaomann, J Am. Chem. Soc. 53 R998, ‘step process as the yield is increased at least 1.931 and Walden and (Jo-worker, J. Am. Chem. ‘one and a half times. Soc 56 10921934). It is advantageous to so choose the concentra The suitability of 1.10-phenanthroline for ‘t'for- of sulphuric acid having regard to the water analytical purpose and a‘so the colouring of ‘ content of the copper salt and, if need be, to bacteria caused Frederick G. Smith and C. A. ‘that oi the g‘ycerine so that a concentration of Getz (Chem. Pay. 16. 113 (1035) to thorouchlv 68-70% results. test the possibility of improving the nhenan The most suitable temperature for the reaction thrnline synthesis with Which up to then the "is Nil-140° C.. i. e. at or just under the boiling yields had merely amounted to '7 to 8% calcu- I‘ 'point of the reaction mixture. For each mol lated on the mononuclear starting product. They of the amino groups capable of condensation, were able to attain yields of about 20% in a ca. 1.5-2 5 mols glycerine and l-l 5 mols nitro three step process whereby a yield of ca. 40% Jbenzene sulphonic acid or arsenic acid are used. was obtained on condensing 8-aminoouinol‘ne 1-1.?5 mol copp er salt per mol of starting product with glvcerine. The authors 11°66. arsenic pent 59 ‘is suflicient. The 8-15 times more sulphuric acid ovide as dehvdroeeneting agent, and the reduc "than starting product guarantees that the reac tion of fl-nitroouino‘ine was carried out with tion mixture liquid is sufficiently thin. iron powder and h"d.Y‘0?h10‘-"lf‘, acid. Kn‘w'onel The improvement in yield is not due merely had already used arsenic acid instead of nitro ‘to an improvement of the isolation of the phenan ben'zene to produce S-nitrcouinOline (‘Ber 29, throline from the reaction mixture, as the addi 705. 18.06). Barrens and Mayer, C. r_. 16, 1428', tion of copper sulphate after the reaction causes 1934.) used sodium nitrcbenzene sulnbonate as nothing like so great an increase in the yield as another water soliible dehvdrogenating agent ‘occurs in the presence of copper salts during for Skraup’s quinoline synthesis. These dehy~ condensation both by the use of arsenic acid and droeenating agents have the advantage over .40 also in particular of nitrobenzene sulphonic acid nitrobenzene that their reduction products can as dehydrogenating agents. be more easily separated from raw phenan~ The following examples should illustrate two throline. However. this is obtained in a very ' methods of carrying out this invention without impure form and the troublesome isolation from limiting it to them. Parts mentioned therein the resinous raw product is an additional diffi 45 are parts by weight and temperatures are given cultv and reduces the yields. in degrees centigrade. It has now been discovered that LIO-phenan throline can be produced with much better yields Example 1 and more easily worked up by condensing 246 parts of nitrobenzene are heated to 100° o-phenylenediamine or S-aminoquinoline with with 620 parts 28% oleum while stirring until glycerine, e. g by means of sulphuric acid, in the a sample of the mixture dissolves clearly in presence of the usual dehydrogenating agents water. ' such as nitrobenzene sulphonic acid or arsenic The mixture is then cooled and 950 parts of acid, if the condensation is done in the presence 64% sulphuric acid, 110 parts of o-phenylenedi of copper-(ID-salts, e. g. copper sulphate or 56 amine and 355 parts of 90% glycerine are added. 2,535,417 3 4 This mixture is then heated to 110-120“ and 300 is heated to 110° and 250 parts crystallised copper parts of crystallised copper sulphate are added sulphate are added whereupon the reaction mix whereupon the reaction mixture becomes thick, ture becomes thick but on further heating again but on further heating again becomes a thin becomes a thin liquid. The mixture is heated for liquid. Afterwards it is heated for 4 hours under 4 hours at 130-140° under re?ux while stirring. re?ux, i. e. at about 140° while stirring. The After this time, a diazotised sample of the re mixture, cooled to about 60°, is then poured action mixture should no longer couple with R into 5,000 parts of water and allowed to stand. salt. When this state is reached, the mixture After about 24 hours the separated black phenan is cooled to 90-100° and poured into 3000 parts throline copper complex salt together with simi 10 water. After standing for 12 hours the separated larly separated hydroxy metanilic acid is ?ltered green-grey complex compound together with off. The sediment is suspended in diluted sul some hydroxy metanilic acid which has also phuric acid and disintegrated by the addition of separated, can be ?ltered oif. The sediment is hydrogen sulphide or by dropping in sodium suspended in diluted sulphuric acid and dis sulphide solution. The precipitated copper sul 15 integrated by the addition of hydrogen sulphide phide is ?ltered, whereupon after treating the or by dropping in sodium sulphide solution. The ?ltrate with animal charcoal, 1.10-phenanthro precipitated copper sulphide is ?ltered off and line is liberated with lyes, for example caustic after treating the ?ltrate with animal charcoal, soda lye, and shaken out with chloroform. After 1.10-phenanthroline is liberated with lyes, e. g. evaporation of the solvent, a reddish coloured caustic soda lye. The free base can then either crystallised mass remains, which, recrystallised be extracted with chloroform and after evapora in water produces a yield of over 30% 1.10 tion of the solvent, recrystallised from ?rstly phenanthroline hydrate. The dehydrated 1.10 water, and then diluted acetone, or it can be phenanthroline melts at 117-118°. - allowed to solidify, ?ltered, distilled in a high Example 2 25 vacuum and ?nally recrystallised from diluted acetone. By the ?rst method a yield of 52-57% A mixture of 900 parts of sulphuric acid, 108 1.10-phenanthroline is obtained in the form of parts of o-phenylenediamine, 320 parts of de its hydrate which is increased to 60-65% by the hydrated glycerine and 300 parts of dry arsenic second method. acid is heated to 100-110° and then 300 parts of 30 What we claim is: crystallised copper sulphate are added. The 1. Process for the manufacture of 1.10 temperature is then raised. At about 130” a phenanthroline by condensation of a starting strong reaction takes place, so that heating must material selected from the group consisting of be discontinued and, if necessary, the mixture o-phenylenediamine and B-aminoquinoline to allowed to cool. On completion of the reaction, 35 gether with glycerine in the presence of a Skraup the reaction mixture is heated for a further 3 dehydrogenating agent selected from the group hours at 140°. The mixture is then cooled to consisting of nitrobenzene sulphonic acid and about 60°, poured in to 5,000 parts of water and arsenic acid, characterised in that the condensa allowed to stand. After about 24 hours, the pre tion is carried out in 60-70% sulphuric acid as cipitated phenanthroline copper complex salt is 40 condensing agent at a temperature of about ?ltered off, suspended in diluted sulphuric acid 120-140" C. and in the presence of an inorganic and sodium sulphide solution is added dropwise. salt of bivalent copper suf?cient in amount to The precipitated copper sulphide is then ?ltered transform all phenanthroline into its copper off and a yield of about 25% of o-phenanthroline complex compound, isolating the phenanthroline is obtained from the ?ltrate by the method de copper complex and separating the 1.10 scribed in Example 1. phenanthroline by decomposition of the complex. Example 3 2. Process as claimed in claim 1 in which 1-l.25 mol of a copper salt is used per mol of the start 184 parts of nitrobenzene are heated to 100° ing material. with 476 parts 26% oleum while stirring until a 3. Process as claimed in claim 1 in which cupric sample of the reaction mixture is clearly soluble 50 sulphate is used. in water. It is then cooled and 965 parts 62% 4. Process as claimed in claim 3 in which cupric sulphuric acid, 144 parts B-aminoquinoline and chloride is used. 235 parts of 90% glycerine are added. (The 8 5. Process as claimed in claim 1 in which the aminoquinoline is obtainable, e. g. from 8-nitro— 1.10-phenanthroline is obtained from the phen quinoline by reduction with iron powder and anthroline copper complex by decomposition by hydrochloric acid according to Claus and Setzer, means of hydrogen sulphide. J. Chemie (2) 53, 400 (1896) or from 8-hydroxy ERNST HODEL. quinoline by reacting with ammonium sulphite HANS GYSIN. solution at 140-150° (N. N. Woroshtzow and J. M. Kogan, B. 65, 142 (1932)). Thereafter the mixture '0 No references cited.