CHAPTER 4 THE ZININ REDUCTION OF NITROARENES H. K. Porter Organic Chemicals Department E. I. dw Pont de Nemours and Co., Inc., Wilmington, Delaware CONTENTS PAGE Inrropuction eo . 456 Mecuanism 60... coe 456 Scorz aNp Lrmrrations Se . 458 Side Reactions oe 460 ‘Dehalogenation s+ ss - 460 Formation of Sulfonic Acid. Se 460 Replacement of Halogen by the Mereapto Group ee 461 Hydroxylation. oo ee - 461 Hydroxylamine Formation =| ss soe 461 Thiosulfonic Acid Formation =. 6. ee 461 Reduction of Azido Groups eee 462 Elimination of a Sulfonie Acid Group... oe | ate Decarbonylation —. toe be 468 Benzotriazole Formation Be 463 Oxidation of Methyl and Methylene». 464 Zinin Reduction of Compounds without a Nitro Group. 464 Reduction of Nitrosoarenes to Arylamines . 5. 464 Cleavage of Azo Groups. re Reduction of Azobenzenes to Hydrazobenzenes : - 464 EXPERIMENTAL CONDITIONS AND PROCEDURES. =... 464 5-Nitro-m-phenylenediamine . 485 Metanilic Acid 2 | Lo 465 Sodium Picramate 45a: : 466 Tapurar Survey. , toe 467 Table I. Reduction of Mononitroarenes and Their Halogen Derivatives | 467 ‘Table II. Reduction of Dinitroarenes and Their Halogen Derivatives . 468 Table III. Reduction of Trinitroarenes . ae 469 Table IV. Reduction of Nitrophenols and Ethers . =. ss. 469, Table V. Reduction of Nitroary! Ketones and Aldehydes. 470 Table VI. Reduction of Nitroarenecarboxylie Acids, Esters, and Amides . 470 Table VIL. Reduction of Nitroarencsulfonic Acids. =. st 47 Table VIII. Reduction of Nitroquinones and Derivatives. 472 ‘Table IX. Reduction of Nitroarylamines : . 414 455456 ORGANIC REACTIONS Table X. Reduction of Nitroaryl Azo Compounds : . 4 Table XI. Reduction of Nitrosoarenes. - ss se £ REFERENCES To TABLES . toe # INTRODUCTION The Zinin reduction is a method for the reduction of nitroarenes by negative divalent sulfur (sulfide, sulfhydrate, and polysulfides). This versatile reaction can be carried out in standard laboratory equipment and has been used for plant-scale manufacture of aromatic amines when other reduction media are destructive to sensitive compounds or result in undesired side reactions. ‘The reaction, first used by Zinin in 1842 to prepare aniline from nitro- benzene, has since been of great importance in the preparation of aro- matic amines. With the advent of catalytic reduction procedures, Zinin’s method has seen less use in the laboratory as a preparative technique. Recently published laboratory texts of organic chemistry often fail to mention this rather simple procedure for the preparation of a host of ordinary or rare amines. Economically, in most instances it has not proved s0 attractive as the iron reduetion method in commercial applications.” but it is used with more sensitive compounds that would not be com. patible with acid media or would be reduced farther than desired by the iron or catalytic hydrogenation process. Refinements in technique? and a better understanding of the reaction mechanism (see below) should make the method attractive for the prep- aration of a variety of amines. A closer look at the technology may lead to the development of processes which offer advantages over many current catalytic and iron reduction methods. For instance, a recent article describes a continuous process for reducing 1-nitronaphthalen: with aqueous sodium disulfide. Several reactions discussed on pp. 460 464 produce products other than the expected amines and should lead t« general preparative methods for materials not readily obtainable by other reduction methods. MECHANISM Tho stoichiometry of the Zinin reduction is illustrated by Zinin’~ original reduction of nitrobenzene by aqueous ammonium sulfide. 4. CgH,NO, + 6S? + 7 H,O > 4 CgH,NH, + 38,0; + 6OH- 1 N, Zinin, J. Prakt, Chem., (1) 87, 149 (1842). 2 P. H. Groggins, Unit Processes in Organic Synthesis, McGraw-Hill, New York, 1958. pp. 186-190. 2 HLT. Stryker, U.S. Pat. 3,223,727 (1965) (C-4., 64, 4051 (1966)]. 4G. M. Tomokkin and B. I. Kissin, Khim, Prom., 8, 79 (1960) {C.4., 85, 469 (1961)THE ZININ REDUCTION OF NITROARENES 487 If the reductant is disulfide, the equation is analogous. CoHyNO, + 8,°° + HO > CgHgNHy + ,0,?° Although earlier studies,'~’ particularly those by Hodgson,** provide insight into the mechanism, the kinetie work of Hojo and co-workers is the most helpful. They worked mostly with disulfide, which reduced nitrobenzene much more rapidly than did sulfide. The medium they used was aqueous methanol, and the rate increased rapidly with increasing concentration of water. They showed that when sufficient alkali is present to keep the equilibrium 8,2> + H,0 = HS; + OH- far on the side of disulfide ion, the rate of reaction is first-order in di- sulfide ion and first-order in nitroarene. Electron-withdrawing sub- stituents speeded up the reaction considerably; the relative rates fitted the Hammett equation well, with p = —3.55. Azoxybenzene is reduced very slowly compared to nitrobenzene. These observations suggest that the rate-determining step is attack of disulfide ion on the nitro group. Probably the first product is a nitroso compound, which is rapidly reduced to a hydroxylamine and then an amine. ArNO, + 8,2> -> ArNO > ArNHOH —> ArNH These kinetic studies suggest to the experimenter that disulfide ion rather than sulfide ion be used; that as high a concentration of water be used as is consistent with complete or partial solution of the nitroarene in the reaction mixture; that enough excess alkali be used to have almost all the reductant present as sulfide ion or disulfide ion; and that excess reductant be used to ensure a rapid reduction that does not stop at an intermediate stage, thus minimizing condensations of intermediates to give azoxy or azo compounds. The uniqueness of the Zinin reduction of nitroarenes, as compared to reduction by iron or catalytic hydrogenation, lies in its lower reduction potential and its narrow useful range of electromotive force. This means that functional groups other than nitro are less likely to be reduced. Moreover, selective reduction of one nitro group in a dinitro- or trinitro- arene is often possible. Some useful generalizations (pp.458~459) often enable 3 11, Goldschmidt and H. Larsen, Z. Phys. Chem. (Leipzig), 71, 437 (1910). © K. Brand, J. Prakt. Chem., [2)74, 449 (1906). 7 LM. Kogan and A. I. Kizber, J. Gen. Chem., 5, 1762 (1935). 8 H, H, Hodgson, J. Soe. Dyers Colour., 58, 246 (1943). * H. H. Hodgson, 1. Chem. Sor., 1944, 75. ° M. Hojo, Y. Takagi and Y. Ogata, J. Amer. Chem, Soc., 82, 2459 (1960),