EXCHANGE 
 
 BOBl'lZWMVd 
 
37 1922 
 UNIVERSITY OF PENNSYLVANIA 
 
 THE 
 
 METHYLATION OF PARA-AMINOPHENOL 
 BY MEANS OF FORMALDEHYDE 
 
 BY 
 
 ERNEST CARL WAGNER 
 
 A THESIS 
 
 PRESENTED TO THE FACULTY OF THE GRADUATE SCHOOL 
 IN PARTIAL FULFILLMENT OF THE REQUIRE- 
 MENTS FOR THE DEGREE OF 
 DOCTOR OF PHILOSOPHY 
 
 1921 
 
UNIVERSITY OF PENNSYLVANIA 
 
 THE 
 
 METHYLATION OF PARA-AMINOPHENOL 
 BY MEANS OF FORMALDEHYDE 
 
 BY 
 
 ERNEST CARL WAGNER 
 
 A THESIS 
 
 PRESENTED TO THE FACULTY OF THE GRADUATE SCHOOL 
 IN PARTIAL FULFILLMENT OF THE REQUIRE- 
 MENTS FOR THE DEGREE OF 
 DOCTOR OF PHILOSOPHY 
 
 1921 
 
ACKNOWLEDGMENT 
 
 The subject of this study was suggested 
 by Dr. W. T. Taggart, under whose super- 
 vision and with whose encouragement the 
 work described was undertaken. 
 
 Much practical help and many useful sug- 
 gestions were given by Dr. H. S. Lukens. 
 
 To these gentlemen the writer takes this 
 opportunity to express his appreciation. 
 
The Methylation of p-Aminophenol 
 by Means of Formaldehyde 
 
 A Study of Certain Methods for the Conversion 
 of the Condensation-products of Formaldehyde 
 and p-Aminophenol into N-Methyl-p-aminophenol 
 
 This paper it divided as follows: 
 
 /- The Condensations of Formaldehyde and 
 Aromatic Amines 
 
 A. Condensations in Neutral or Alkaline Media 
 
 B. Condensations in Acid Media 
 
 C. Summary of Important Condensations and 
 
 Secondary Reactions 
 
 //- Methylation of Aromatic Amines by Means 
 of Formaldehyde 
 
 III- Experimental Results on the Methylation of 
 p-Aminophenol by Means of Formaldehyde 
 
 IV- Summary 
 
 I. The Condensations of Formaldehyde and Aromatic Amines 
 
 In the condensations of formaldehyde with the amines, the 
 fundamental change consists in the splitting out of the elements 
 of water, with the result that a methylene-group is introduced. 
 Typically the necessary hydrogen atoms are displaced from an 
 amino-group, or from two imino-groups. It is characteristic of 
 certain condensations, however, that only nuclear hydrogen 
 atoms are involved. The course of the condensation depends 
 upon (a) the nature of the medium in which condensation oc- 
 curs, i.e., whether neutral, alkaline, or acid, (b) the relative pro- 
 portions of amine and aldehyde, (c) the presence of substances 
 with which further reaction may occur, and (d) the influence of 
 substituent groups present in the amine molecule. 
 
METHYI<ATION OF PARA-AMINOPHENOI, 
 
 With respect to these influences, it can be said introductorily 
 that what may be termed the normal condensation occurs in 
 neutral or alkaline solution, that which results in presence of 
 acid being essentially different. The relative amounts of amine 
 and aldehyde present determine whether one or two amine mole- 
 cules will be involved in the condensation, and also, when an 
 excess of amine-salt is present, whether or not further condensa- 
 tions of the primary product with uncondensed amine will occur. 
 
 The influence of substituent groups upon aldehyde condensa- 
 tions was observed by Kibner 1 who found that trichloraniline 
 did not react with chloral, though less chlorinated anilines con- 
 densed. In other cases, such as o-dimethyltoluidine, a condens- 
 ing agent (zinc chloride) may be required. 2 It has been found 
 also that tribromaniline does not condense with formaldehyde, 
 either under ordinary conditions, or in a sealed tube at 250. 
 The effect of the substituent bromine-atoms in this case is so 
 strong that the action of an excess of bromine upon a benzol 
 solution of anhydroformaldehydeaniline not only brominates the 
 aromatic nucleus, but to a certain extent eliminates the methyl- 
 ene-group previously united with the nitrogen-atom. This is 
 evidenced by the appearance of tribromaniline as a constant pro- 
 duct of this bromination. 
 
 A Condensations of Formaldehyde and Aromatic Amines in 
 Neutral or Alkaline Media. 
 
 The essential reactions which may occur, depending upon the 
 nature of the amine, and upon the relative proportions of amine 
 and formaldehyde, are the following : 
 
 (a) C 6 H 6 .N|H 2 T6|CH 2 = C 6 H 6 .N:CH 2 + H 7 O 
 
 ( anhyd rof ormaniline ) 
 
 , 
 C 6 H 6 NH!H 
 
 (methylene-di-phenamine base) 
 
 C ' > N 
 
 R > NH 
 
 $&**& ______ i 
 
 (tnethylene-di-phenamine base) 
 1 Annal., 302, 349. 
 'Alexander, Ber., 25, 2408 (1892). 
 
MKTHYLATION OF PARA-AMINOPHENOI, 
 
 Compounds of these types are more or less generally referred 
 to as "SchifFs Bases," which include also the condensation- 
 products of other aldehydes. 
 
 The earliest known and simplest formaldehyde condensation 
 of type (a) among aromatic amines was studied by Pratesi and 
 Tollens 3 in the case of aniline. Anhydroformaldehydeaniline, 
 or anhydroformaniline, is thus obtained in the trimeric form 
 (C 6 H 5 N.CH 2 ) 3 . 4 Polymerization occurs also with other amines, 
 such as the toluidines 5 and p-aminophenol. 6 The existence of two 
 forms of such compounds, having different melting points and 
 solubilities, has been observed in several cases. This was attributed 
 at first to different degrees of polymerization. It was shown by 
 Bischoff, however, that (CH 3 .C 6 H 4 .N.CH,) n exists in two forms, 
 both of which have the same molecular weight, corresponding to 
 the formula (CH 3 .C 6 H 4 .N.CH 2 ) 3 . He concluded that the two 
 forms must be geometrical isomers of the cis and trans types with 
 respect to the CH 3 .C 6 H 4 -groups attached to the [ N.CH 2 -] 3 
 ring. Anhydroformaniline likewise probably exists in two forms. 
 Dimeric forms of these anhydro-bases, such as 
 
 (CH 3 .C 6 H 4 .N.CH 2 ) 2 , 
 
 or structurally, CH 3 .C 6 H 4 .N<^ 2 >N.CH 4 .CH S , 
 
 have been reported. 7 
 
 The general reaction of which the formaldehyde-aniline con- 
 densation serves as a type was soon applied to the toluidines, etc., 
 by Wellington and Tollens, 8 and has since that time been extended, 
 where applicable, to apparently all amines of importance, both 
 aliphatic and aromatic, as well as to many heterocyclic compounds. 
 
 3 Pratesi, Gazz. chint. ital., 14, 351 (1884); Tollens, Ber., 17, 653 (1884); 
 18,3309(1885). 
 
 * Miller and PlochU, Ber. y 25, 2020, (1892); Bischoff, Ber., 3!, 3248 
 (1899). 
 
 6 Bischoff. /. c. 
 
 D. R. P., 68707. 
 
 7 Ber. y 31, 2037, 3248; AnnaL, 256, 288. 
 
 8 Bcr., 18,3298(1885). 
 
F PARA-AMINOPHENOI, 
 
 Condensation of two equivalents of amine and one of formalde- 
 hyde is of type (b), and yields methylene-di-imine compounds of 
 the type-formula Ar.NH.CH 2 .NH.Ar. Thus two molecules of 
 aniline and one of formaldehyde form methylenediphenyldi-imine, 
 or dianilinomethane : 8 C 6 H 5 .NH.CH 2 .NH.C 6 H 5 . By boiling this 
 compound in alcohol, it is transformed into anhydroformaniline. 10 
 Exactly analogous condensations occur with other amines. 11 
 
 The most interesting reaction of the di-imine bases occurs when 
 they are heated with amine-salts. Diamino-diphenylmethane 
 derivatives are thus formed, by a rearrangement which recalls the 
 transformation of hydrazobenzene to benzidine : 12 
 
 Ar.NH.CH 2 NH.Ar. *-> Ar.NH.CH 2 .Ar.NH 2 
 
 H* NH 2 .Ar.CH 2 .Ar.NH 2 . 
 
 As these compounds are formed directly when condensation is 
 conducted in presence of free acid, and with base in excess of 
 formaldehyde, the secondary reaction just given belongs more 
 properly to Section B, where its probable mechanism will be 
 indicated. 
 
 Condensations of types (a) and (b) may occur simultaneously, 
 one or the other predominating; excess of aldehyde favors the 
 first, while excess of amine favors the second. 13 
 
 Condensations of type (c) are characteristic of secondary 
 amines, and are in no essential manner different from the pre- 
 ceding. The methyltoluidines, for example, condense with 
 formaldehyde to form (C 7 H 7 .N.CH 3 ) 2 CH 2 . 14 When heated with 
 amine-salts, these compounds, like those obtained from primary 
 amines, are rearranged to form dialkylamino-diphenylmethane 
 derivatives. 
 
 Compounds intermediate between the methylene-di-imine 
 bases (Ar.NH.CH 2 NH.Ar.), and the diamino-diphenylmethanes 
 
 9 Pratesi, Bischoff, /. c. 
 
 10 Eberhardt and Welter, Ber., 27, 1804 (1894). 
 
 11 Eibner, Annal., 302, 349 (1898): Bischoff, /. c.\ Bischoff and Reinfeld, 
 Ber., 36, 41 (1903); D. R. P. 138393, etc. 
 
 12 D. R. P. 63081, 107718. 
 
 13 Eibner; Eberhardt and Welter, /. c. 
 
 14 Braun, Ber., 41, 2145 ( I 98). 
 
METHYIyATlON OF PARA-AMINOPHENOI, 
 
 (NH 2 .Ar.CH 2 .Ar.NH 2 ), viz., the aminobenzylanilines (NH 2 .Ar.- 
 CH 2 .NH.Ar.), are formed when an anhydro formaldehyde-base is 
 heated with an amine-salt : 15 
 
 C 6 H 5 .N:CH 2 + H.C 6 H 4 .NH a (HCl)~- 
 
 C 6 H 5 .NH.CH 3 .C 6 H 4 .NH,(HC1). 
 
 Condensations of nuclear-substituted amines proceed often in 
 the normal manner; o-nitraniline, for example, yields 
 
 Similar condensations occur with halogenated amines, aminoben- 
 zoic acids, aminosulphonic acids, benzidine, tolidine, phenetidine, 
 etc. 
 
 It is of great practical importance that the methylene-group of 
 the diphenylmethane compounds can be condensed with a third 
 amine-molecule by oxidation, forming triphenylmethane deriva- 
 tives, among which fuchsine and the homologous pararosanilines 
 are included. 17 
 
 Primary condensation-products of the type Ar.N :CH 2 , although 
 probably cyclic polymers devoid of double bonds, are able to unite, 
 by addition, with several substances, the most important of which 
 are (i) hydrogen, (2) sulphurous acid or bisulphites, and (3) 
 hydrocyanic acid. These additions occur according to the follow- 
 ing equations : 18 
 
 (1) Ar.N:CH 2 -f 2H .= Ar.NH.CH 3 
 
 (2) Ar.N:CH 2 + NaHSO 3 = Ar.NH.CH 2 SO 3 Na 
 
 (3) Ar.N:CH 2 + HCN = Ar.NH.CH 2 .CN 
 
 The bisulphite compound contains a replaceable SO 3 H or 
 -SO 3 Na group : 19 by interaction with cyanide a phenylglycineni- 
 trile results: 
 
 Ar.NH.CH 2 .SO,Na + NaCN = Ar.NH.CH 2 .CN + Na 2 SO 3 . 
 The synthesis of phenylglycine and its homologues is thus possible 
 
 D. R. P. 87934- 
 
 16 Pulvermacher, Ber,, 25, 2764526, 955. 
 
 17 D. R. P. 53937, 55565, 61146, 67013, 73092. 
 
 18 Miller and Plochl, Ber., 25, 2020 (1892); Eibner, AnnaL, 3x6, 89 
 (1901); Lcpetit, Atti. accad. Lincei, 26, I, 126 (1917); Gazz. chitn. ital., 47, 
 I, 197 (1917); C. A., 1918, 366. 
 
 19 Knoevenagel, Ber., 37, 4073 (1904). 
 
PARA-AMINOPHENOI, 
 
 by a convenient method, as the products may be obtained directly 
 by proper treatment of amine, cyanide, formaldehyde, and alkali. 20 
 
 Preparation of phenylglycine-o-carbonic acid is accomplished by 
 a similar process, starting with anthranilic acid. 21 Condensations 
 of formaldehyde with anthranilic acid or its esters have been 
 rather carefully studied. 22 
 
 Union of the anhydro-base Ar.N :CH 2 with hydrocyanic acid or 
 bisulphite may take place either after isolation of the base, or in a 
 mixture of amine, formaldehyde, and cyanide or bisulphite. In 
 the latter case it is to be supposed that the cyanhydrin or aldehyde- 
 bisulphite is primarily formed, and reacts with the amine : 
 
 iOH + HiN.H.Ar 
 CH 2 + HCN -* CH 3 < 
 
 Ar. NH.CH 2 . CN -f- H 2 O 
 CH,0 + NaHS0 3 -~ CH a <j^---- II - iNH - Ar 
 
 w v^ojlN 3, 
 
 *Ar.NH.CH a .SO 3 Na + H,O. 
 
 The corresponding bisulphite compound of p-aminophenol is 
 HO.C 6 H 4 .NH.CH 2 .SO 3 Na. It may be made either by dissolving 
 the condensation-product HO.C 6 H 4 .N :CH 2 in bisulphite solu- 
 tion, 23 or by dissolving p-aminophenol in formaldehyde- bisulphite 
 solution. The addition-product readily evolves sulphur dioxide 
 when heated with acids, and may therefore be represented as a 
 loose compound of the formula (HO.C 6 H 4 N :CH 2 ) NaHSO 3 . Its 
 alkaline solution exhibits reducing properties, and it has been 
 recommended as a photographic developer under the name 
 "Eurekin." The general similarity of this compound and the 
 developer "Metol," as shown by the formulas 
 
 20 JBer., 27, 1805; 3 9, 987; D. R. P. 135332, 145376, etc. 
 31 D. R. P. 117924, 120105, 158090, 151538. 
 
 22 Erdmann, //*' Ch., (2), 68,387, 569; Mehner, ib., (2), 63, 244565, 
 533J Goldschmidt, Chem. Ztg., 26, 179; Haller and Fiesselmann, Annal., 
 324, n8; Bischoff and Reinfeld, Ber., 35, 3440; 36, 41. 
 
 23 D. R. P. 68707. 
 
METHYI.ATION OF PARA-AMINOPHENOI, 
 
 (p-HO.C 6 H 4 N:CH 2 )NaHS0 3 , (p-HO.C 6 H 4 .NH.CH 3 ) 2 H 2 SO 4 , 
 
 (Eurekin) (Metol) 
 
 seems to be of little significance in the preparation of the latter. 
 
 B Condensations of Formaldehyde and Aromatic Amines in 
 
 Acid Media." 
 
 The condensation of aniline and formaldehyde in presence of 
 hydrochloric acid yields a chlorinated product C 6 H 5 .NH.CH 2 C1. 25 
 This compound is itself of no great importance, but derives 
 interest from the fact that it readily loses a molecule of hydro- 
 chloric acid, especially in contact with alkalies, and passes into 
 the anhydride of p-aminobenzyl alcohol : 
 
 NHjHHiCl -f ! OiCH, NH. 
 
 CH 2 - 
 
 (exochlormethyl- (anhydroamino- 
 
 aniline) benzylalcohol) 
 
 These reactions occur strikingly in the case of methylaniline, 28 
 the exochlormethyl-derivative of which separates as white needles 
 when the secondary base is allowed to stand with formaldehyde 
 in dilute hydrochloric acid solution. The product, when treated, 
 in solution, with alkali, is transformed into white, amorphous 
 anhydro-p-methylamino-benzylalcohol. Analogous reactions occur 
 also with ethylaniline 27 and other primary and secondary amines. 
 That anhydroaminobenzylalcohol is a para-compound is shown by 
 its reduction to p-toluidine. 28 The anhydroaminobenzylalcohols 
 are characterized by their insolubility in water and in the usual 
 
 24 D. R. P. 53937, 70402, 95184, 95600, 96851, 96852, 97710; Ber., 31, 
 1037 (1891)); 33,250(1901); C. C., 1898, 11,159; 1912, II, 2070; 1906, I, 
 1416; C. A., 11, 582 (1917.) 
 
 25 Goldschmidt, Chem. Ztg., a4, 284 (1900); D. R. P. 96851; cf. Raikow, 
 Chem. Ztg., 20, 307 (1896). 
 
 26 Goldschmidt, /. c. 
 
 31 Goldschmidt, Chem. Ztg., 26, 606, (1902). 
 18 D. R. P. 83544. 
 
METHYI,ATION 01? PARA-AMINOPHENOI, 
 
 organic solvents ; they are soluble in dilute hydrochloric or other 
 mineral acid, with formation of the corresponding salt. The 
 anhydro-alcohols derived from primary amines are themselves 
 secondary amines, and form nitrosamines. The anhydroamino- 
 benzylalcohols are obtained in more or less polymerized condition, 
 the degree of polymerization varying with the amount of acid 
 present during their formation. 29 The simplest member is 
 obtained in polymerized form from the true alcohol, 
 NH 2 .C 6 H 4 .CH 2 OH, by heating with acid, 30 as well as by treatment 
 of exochlormethylanilme, C 6 H 5 .NH.CH 2 C1, with alkali. 
 
 The anhydroaminobenzylalcohols may be prepared also from 
 condensation-products of the types Ar.N :CH 2 and (Ar.NH) 2 CH, 
 by action of strong acids. Thus anhydroformaniline, in contact 
 with strong hydrochloric acid, is gradually transformed into exo- 
 chlormethylaniline, which is converted by alkali to anhydro-p- 
 aminobenzylalcohol. 31 By action of glacial acetic acid in the cold, 
 however, an isomeric form of anhydroformaniline results, having 
 the probable formula C 6 H 5 NH.CH 2 C 6 H 4 .N :CH 2 , 32 and possessing 
 the ability for further condensations. 
 
 Typical condensations occur with /3-phenylhydroxylamine, 88 
 and with p-substituted amines such as p-toluidine, xylidenes, 
 and p-chloraniline. 34 The products resemble the other anhydro- 
 aminoalcohols ; that from p-chloraniline is exceptional in being 
 crystallizable. In the same way p-aminophenol yields an 
 amorphous base of the probable formula, 35 
 
 NH 
 HO.C 6 H,< I 
 
 CH 2 
 
 This differs from the anhydroaminobenzylalcohols mentioned 
 above by its solubility in alkalies as the phenolate; it is precipi- 
 tated from acid solution by sodium carbonate. 
 
 D. R. P. 96851. 
 
 90 D. R. P. 83544. 
 
 11 D. R. P. 95184. 
 
 M D. R. P. 121506. 
 
 M D. R. P. 87972. 
 
 84 D. R. P. 122474. 
 
 K Orloff, "Formaldehyde," Leipzig, (1909) p. 95. 
 
 8 
 
METHYLATION OF PARA-AMINOPHENOL 
 
 With salts of aromatic amines, the anhydroaminobenzylalcohols 
 combine to form diphenylmethane derivatives, a reaction of 
 importance : 38 
 
 H.C 6 H 4 .NH,(HC1) 
 CH, 
 
 By use of nuclear-substituted and N-alkylated amines, unsym- 
 metrically substituted diphenylmethane derivatives may be 
 obtained. 
 
 It will be recalled that diphenylmethane derivatives are formed 
 (page 4) in another way, by heating the methylenedi-imine bases 
 with excess of amine-salt, or with amine and acid, a transforma- 
 tion like that of hydrazobenzene to benzidine : 
 Ar.NH.CH 2 .NH.Ar. -> Ar.NH.CH 2 .Ar.NH 2 
 
 -w NH 2 .Ar.CH 2 .Ar.NH 2 . 
 
 This transformation has been studied for o-nitraniline by Meyer 
 and Rohmer, 37 and for several secondary amines by Braun. 38 
 It appears that the exochlor-compound is first formed, with 
 splitting-off of a molecule of amine. The former may then pass 
 into the anhydroaminobenzylalcohol, reaction of which with the 
 amine first liberated yields the diphenylmethane compound which 
 constitutes the end-product. For the simplest case the trans- 
 formation may be indicated by the scheme : 
 
 C 6 H 5 NH CHCD C 6 H 5 .NH.CH 2 .C1 C 6 H 4 
 
 C 6 H 5 NH >C1 * C 6 H 5 .NH,.HC1 --- ' CH, 
 
 This general process is susceptible of many modifications. It is 
 most simply carried out in a single operation, by interaction of 
 formaldehyde and excess of amine in presence of acid. When 
 mixed products are desired, the di-imine is first produced, and is 
 further condensed with the salt of another amine. 
 
 w D. R. P. 96762. 
 
 n Ber. t 33, 250 (1901). 
 
 88 Ber., 4x, 2145 (1908.) 
 
M3THYLATION OF PARA-AMINOPHNOI< 
 
 The same products may be obtained in still another way, from 
 the p-aminobenzylaniline derivatives, NH 2 .Ar.CH 2 .NH.Ar, 39 
 which are formed by interaction of amine-salts with bases of the 
 type Ar.N :CH 2 (pages 4 and 5). The p-amino-benzylaniline thus 
 obtained, when heated with amine and hydrochloric acid, yields a 
 diphenylmethane derivative, with elimination of a molecule of 
 amine : 
 
 NH 2 .C 6 H 4 .CH 2 .NH.C 6 H 5 + H.C 6 H 4 .NH 2 (HC1) * 
 
 NH 2 .C 6 H 4 .CH 2 .C 6 H 4 .NH 2 (HC1) + C 6 H 5 .NH 2 . 
 
 The anhydroaminobenzyl (or homologous) alcohols show a 
 characteristic reaction with /?-arylhydroxylamines, by which 
 result the p-amino-benzaldehydes : 
 
 NH 
 C 6 H 5 .NHOH + I >C 6 H,~ C 6 H 5 .N:CH.C 6 H 4 .NH a 
 
 CH 2 
 
 (H20) 
 
 ^ C 6 H 5 .NH 2 + OHC.C 6 H 4 .NH 2 . 
 
 The same products are obtained by suitable reduction of nitro- 
 compounds in neutral solution and in presence of formaldehyde. 
 
 While the secondary amines condense with formaldehyde in the 
 normal manner, by virtue of the presence of amino-hydrogen, the 
 tertiary amines show a different behavior. Dimethylaniline, con- 
 densed with formaldehyde in acetic acid solution, yields tetra- 
 methyldiaminodiphenylmethane, 
 
 (CH 3 ) 2 N.C 6 H 4 .CH 2 .C 6 H 4 .N(CH 3 ) 2 . 40 
 
 The m-aminophenols, and the corresponding cresols, react in the 
 same way. 41 By dehydration and oxidation, the products of such 
 condensations yield the pyronines. 42 
 
 The m-diamines condense similarly to form diphenylmethane 
 derivatives, from which acridine compounds are obtainable by loss 
 of ammonia and by oxidation. 43 The o-diamines yield imidazole 
 compounds. 44 
 
 39 D. R. P. 87934, 104230, 105797, 108064, 109498. 
 
 40 Mohlau and Heinze, Ber., 35, 359 (1902); cf. Pinnoff, Ber., 27, 3166 
 (1894). 
 
 41 D. R. P. Anm., 5528; D. R. P. 58955, 75373; Ber., 27, 1894 (1894); /. 
 pr. Ch,, 54, 217 (1896). 
 
 42 D. R. P. 59003, 63081, 75138, 84988, 99613- 
 
 "Orloff, "Formaldehyde," Leipzig, 1909, pp. 97, 115-123, gives a general 
 account, together with some of the numerous patents. 
 44 O. Fischer, Per., 25, 2711; 32, 245. 
 
 10 
 
METHYIvATlON OF PARA-AMINOPHENOI, 
 
 Amines of the naphthalene series condense with formaldehyde 
 in acid solution with elimination of ammonia and water. Double 
 junction between two naphthalene nuclei at their a and ft positions 
 is effected through a -CH 2 - and an -NH- group. When. 
 however, the /^-position is occupied, as by -SO 3 H, the amino- 
 group is not involved, but the two nuclei are united through 
 -CH 2 - attached at the 4-positions. 45 
 
 It will not be profitable to extend further the list of condensa- 
 tions, though it is not even approximately complete. A brief and 
 fairly comprehensive survey of the subject (up to about 1908) is 
 given by Orloff. 46 Later work is recorded in the academic and 
 patent literature. 
 
 C Summary of Important Condensations of Formaldehyde 
 and Aromatic Amines*' 
 
 (i) Primary Condensations 
 
 (a) In absence of acids, one molecule of formaldehyde 
 and one molecule of primary amine react to form 
 readily polymerized N-methylene-amines (anhydro- 
 formaldehydeamines) : 
 
 Ar.N:H 2 " o!CH 2 - Ar.N :CH 2 + H 2 O 
 
 (b) In absence of acids, one molecule of formaldehyde 
 and two molecules of primary or secondary amine 
 react to form methylene-di-imino bases (methylene- 
 diphenamines, dianilinomethanes") : 
 
 Ar.NHiH Ar.NH 
 
 Ar.NHiH U ; LH * ~~* Ar.NH >Li1 ' 
 
 Ar 
 
 R >N;H 
 
 ^>NJH 
 
 Ar 
 
 R> N \ 
 O CH, ^CU, + H,O 
 
 Ar 
 
 (c) Tertiary amines condense to form diphenylmethane 
 
 derivatives : 
 
 "Morgan, Proc., 16, 131; i95, 132 (1897); /. C. 5., 77, 814; 73, 536; 
 Reed, /. pr. Ch., 35, 298; Bucherer and Seide, Ber. t 40, 859; Senier and 
 Austin,/. C. S., QI, 1233; D. R. P. 84379. 
 46 /. c. pp. 81-123. 
 * 7 Cf. Friedlander, V. p. 5. 
 
 II 
 
METHYLATION OF PARA-AMINOPH^NOI, 
 
 R,N.Ar.iH , 
 
 R 2 N.Ar.JH ;; 
 
 (d) In presence of acids, one molecule of amine and 
 one of formaldehyde unite to form (in the case of 
 HC1) the exochlormethylamino-compounds, which 
 are converted by loss of hydrochloric acid into the 
 reactive anhydroaminobenzyl alcohols. These are 
 para-compounds, unless the para-position is initially 
 occupied, in which case analogous compounds result 
 with the -CH 2 - group otherwise disposed : 
 
 Ar.NH:ILH : Cl + : O!CH 2 
 
 -HCI NH 
 
 Ar.NH.CH a Cl Ar< I 
 
 CH 2 
 
 (2) Secondary Condensations 
 
 (a) The anhydro formaldehyde-amines unite with amine- 
 
 salts in the cold to form p-aminobenzylaniline 
 derivatives : 
 Ar.N:CH 2 -f H.Ar.NH 2 (HCl) *-+ 
 
 Ar.NH.CH 2 .Ar.NH 2 (HCl). 
 
 (b) The p-aminobenzylanilines unite with amine-salts in 
 
 acid medium, and at higher temperatures, forming 
 diphenylmethane derivatives, with elimination of a 
 molecule of amine: 
 Ar.NH.CH 2 .Ar.NH 2 m ^ Ar.NH, 
 NH 2 .Ar.H. NH 2 .Ar.CH 2 .Ar.NH 2 
 
 (c) The methylenedi-imine bases, when heated with 
 amine-salts, pass into corresponding diphenyl- 
 methane derivatives by rearrangement : 
 Ar.NH.CH 2 .NH.Ar. **-* 
 
 NH 2 .Ar.CH 2 .NH.Ar *H NH 2 .Ar.CH 2 .Ar.NH 2 . 
 
 (d) The anhydroaminobenzylalcohols react with amine 
 salts to form diphenylmethane derivatives: 
 
 -f H.A 
 CH, 
 
 NH 
 
 12 
 
OF PARA-AMINOPHENOI, 
 
 II. Methylation of Aromatic Amines by Means of Formaldehyde 
 
 Among the aromatic amines, the time-honored method of 
 alkylation employs the alkyl halides. Much more convenient 
 than this method, however, is that in which an alkyl sulphate, and 
 especially methyl sulphate, is the active agent. 48 This method is 
 coming into increasingly wide use, because of the activity of 
 methyl sulphate, and because of the relative simplicity of the oper- 
 ations. The methylation of p-aminophenol to N-methyl-p-amino- 
 phenol may be accomplished by this means, which is probably that 
 by which the process is now conducted commercially. Methylation 
 may be effected similarly by the use of the methyl ester of 
 p-toluene-sulphonic acid. 49 
 
 Other methods for conversion of primary to secondary amines 
 include the following : 
 
 (1) Action of methyl alcohol in presence of concentrated 
 sulphuric acid. 50 
 
 (2) Hydrogenation of Schiff's bases catalytically, in presence 
 of nickel 51 or metallic oxides. 62 
 
 (3) Alkylation of primary to secondary amines through 
 action of alkyl iodides upon SchifFs bases. 83 This method 
 involves intermediate formation of unstable quaternary 
 compounds by addition of alkyl iodides to bases of the 
 type R.N:CHR'. The quaternary salts, by hydrolysis, 
 yield secondary amine and aldehyde : 
 
 R.N:CHR' + R"I 
 
 H S O R>NH -f CHO.R' + HI 
 
 ^Ullman, Annal., 327, 164 (1903); Meldola and Hallely, /. C. S., 
 I9I2T, 912; Werner,/. C.S., 105, 2762 (1914); Havasand Guyot, Chem. Ztg., 
 37, 812; Shepard, /. A. C. S., 38, 2507 (1916); Klemenc and Edhoffcr, 
 Monats., 38, 553 (1918.) 
 
 49 Ullmann and Wenner, Annal., 327, 120 (1903); Weyl, "Method**," 
 //, 1269 (1911.) 
 
 50 D. R. P. 288825. 
 
 61 Maihle, Bull. Soc. chim., 25, 321 (1919). 
 
 M E. P. 124219. 
 
 M Decker and Becker, Annal., 395, 362. 
 
 13 
 
METHYI,ATION OF PARA-AMINOPHENOI, 
 
 Among the secondary amines prepared by this method are 
 methyl- and ethyl-aniline from benzylidine-aniline, and 
 methyl-p-toluidine from benzylidine-p-toluidine. 
 (4) Condensation of primary amine and phenol. 54 N-methyl- 
 p-aminophenol may be prepared in this way from hydro- 
 quinone and methylamine : 
 
 HO.C 6 H 4 .iOH"TNH;H.CH 3 ^ 
 
 " HO.C 6 H 4 .NH.CH S + H 2 O 
 
 A somewhat similar method involves the interaction of 
 p-chlor-phenol and methylamine: 55 
 
 HO.C 6 H 4 .;CTT~HT NH.CH 3 
 
 HO.C 6 H 4 .NH.CH 3 + HC1 
 
 These methods are more properly described as arylations 
 of aliphatic amines than as alkylations of aromatic 
 amines, though this distinction has no significance so far 
 as concerns the products. 
 
 Consideration of the several primary condensation-products 
 of formaldehyde and the aromatic amines suggests four ways 
 in which the introduced methylene-group might be changed to 
 a methyl-group : 
 
 1 I ) Hydrogenation of the anhydro formaldehyde-amines : 
 
 Ar.N :CH 2 + 2H **-> Ar.NH.CH 3 
 
 (2) Reduction of the exochlormethyl-amines obtained by 
 condensation in acid solution: 
 
 Ar.NH.CH 2 Cl + 2H *> Ar.NH.CH 3 + HC1 
 
 (3) Reduction of the bisulphite addition-products of the an- 
 hydro formaldehyde-amines : 
 
 Ar.NH.CH 2 .SO 3 Na + 2H - Ar.NH.CH 3 + NaHSO 3 
 
 (4) Hydrolysis of the hydrocyanic acid addition-products 
 of the anhydroformaldehyde-amines, and elimination of 
 carbon dioxide by heat : 
 
 Ar.NH.CH 2 .CN M> Ar.NH.CH 2 .COOH 
 
 *-* Ar.NH.CH 3 + CO 2 . 
 
 64 D. R. P. 260234- Harger,/. A. C. S., 41, 270 (1919). 
 66 D. R. P. 205415. 
 
METHYXATION OF PARA-AMINOPH3NOI, 
 
 A brief discussion of methods hitherto applied for reactions 
 such as the foregoing will be given first, and will be followed by 
 a description of experiments on the methylation of p-aminophe- 
 nol by these methods. This reaction was chosen because it ap- 
 pears that the indicated methylation has not been effected by 
 the above methods (except the last), and because the product, 
 N-methyl-p-aminophenol, is a compound of considerable interest, 
 its sulphate being the photographic developer known as "Metol." 
 
 (i) Hydrogenation of the Anhydroformaldehyde-bases, i. e., 
 of the Group -N: CH- 
 
 The methods by which this reduction has been accomplished 
 include the following : 
 
 (a) Reduction by Sodium-amalgam, or by Sodium, and Ab- 
 solute Alcohol 
 
 These two methods constitute classic means for effecting this 
 hydrogenation. 56 Fischer, avoiding the use of acids because of 
 their decomposing effect upon the -N:CH- group, used the 
 above agents for reductions such as that of benzylidene-aniline 
 to benzylaniline. As is well known, the intensity of the reduction 
 may be modified by use of different alcohols. 57 Attempts to re- 
 duce the compound HO.C 6 H 4 .N :CH 2 by these means met with 
 no success. 
 
 (b) Reduction by Means of Zinc-dust and Alkali 
 
 This method is the subject of several patents, dealing with the 
 production of secondary from primary amines. 58 The alkylation 
 or arylation is best carried out by interaction of amine and alde- 
 hyde in presence of excess of reducing agent; the medium for 
 the reaction is water, alcohol (or acetic acid, but not strong 
 acids.) 59 These methods do not seem to have come into general 
 use, and are probably not highly efficient: several attempted 
 methylations of aniline gave only small yields of methylaniline. 
 
 The reduction of benzylidine-p-aminophenol by means of zinc- 
 
 56 O. Fischer, Ber., 19, 748 (1886); Annal., 241, 328 (1887); 245, 279 
 (1888); Miller and Plochl, Ber., 25, 2020 (1892). 
 
 57 See, e. g., Miller and Plochl, /. c. 
 
 M D. R. P. 75854, 105345; Prudhomme, Bull. soc. chim., 23, 69 (1905), 
 59 E. P. 102834, A. P. 1221077; /. C. S., 115, 198. 
 
 15 
 
ME)THYI,ATION OF PARA-AMINOPHENOI, 
 
 dust and sodium hydroxide, on the other hand, takes place without 
 difficulty, 60 giving good yields of benzyl-p-aminophenol. In 
 view of this fact, it is interesting to record that methylene-p- 
 aminophenol resisted all efforts at reduction by the same process. 
 
 (c) Reduction by Zinc in Acid Medium 
 
 Miller and Plochl 61 showed that anhydro formaldehyde-aniline 
 can be reduced to methylaniline by hydrochloric acid and zinc- 
 dust. Goldschmidt 62 carried out the same reduction with tin and 
 hydrochloric acid. No yields are stated for these reductions. 
 
 By reduction of methyl ene-p- aminophenol with zinc-dust and 
 acid, a partial conversion to N-methyl-p-aminophenol was ob- 
 tained, as will appear in the experimental part (section III). 
 
 (d) Reduction Electrolytically in Alkaline Medium 
 
 By this method Brand and Honig 63 obtained benzylmethylamine 
 and benzyl-p-aminophenol by the normal course of the reduction, 
 and o-aminophenol and toluene from benzal-o-aminophenol. The 
 writer was able to reduce benzylidine-p-aminophenol in this way, 
 but methylene-p-aminophenol was not hydrogenated. 
 
 (e) Reduction Electrolytically in Acid Solution 
 Reduction under these conditions suffers the disadvantage that 
 
 the operation of necessity extends over a considerable period of 
 time, during which certain changes incident to the contact of the 
 condensation-product and acid are in progress. It is therefore 
 thought necessary to maintain a low temperature so long as acid 
 and condensation-product are in contact. According to a recom- 
 mended procedure, 64 the condensation-product is dissolved in 50 
 per cent sulphuric acid at -12, and electrolysis is conducted at 
 or below o, using a cathode of lead, copper, nickel, or mercury. 
 In this way both aliphatic and aromatic amines may be alkylated 
 or arylated. 
 
 Numerous reductions of methylene-p-aminophenol by a simi- 
 lar process were carried out, using generally 40 per cent sul- 
 
 60 D. R. p. 211869, 
 
 61 /. c. 
 
 62 Chem. Ztg., 28, 1229 (1904). 
 
 63 Zeit. electroch., 18, 745. 
 
 64 D. R. P. 143197. 
 
 16 
 
METHYLATION OF PARA-AMINOPHENOI, 
 
 phuric acid and a cathode of lead. Certain of the trials were 
 partially successful, while others, intended to be identical, were 
 attended, so far as could be observed, and for reasons which were 
 not discovered, by no absorption of hydrogen, and by the forma- 
 tion of no detectable secondary amine. The process showed no 
 uniform improvement when conducted at low temperature. 
 
 (f) Electrolytic Reduction of Nitro-compounds in Presence 
 of Formaldehyde 
 
 Lob 65 and Goecke 86 carried out reductions of nitrotoluene in 
 hydrochloric acid-alcohol solution, with a lead cathode, and in 
 presence of an excess of formaldehyde. From p-nitrotoluene 
 there were obtained dimethyl-p-totuidine (about 40 per cent), and 
 another compound, called by Lob dimethylditoluidine, and by 
 Goecke trimethylenetritoluidine (but which, it would appear, 
 was probably an anhydroaminobenzyl alcohol). 
 
 This process was applied to p-nitrophenol, both in presence of 
 one equivalent of formaldehyde, and of an excess. In neither 
 case could any mono-methyl-derivative be isolated, though some 
 dimethyl-p-aminophenol was obtained; under the first-mentioned 
 conditions some p-aminophenol resulted by simple reduction of 
 p-nitrophenol. Similar reduction of p-nitrosophenol in presence 
 of formaldehyde likewise failed to produce secondary amine. 
 
 (g) Reduction by Sodium Hydrosulphite 
 
 The applicability of sodium hydrosulphite for reduction of 
 methylene-amines might appear a priori improbable in view of 
 the readiness with which these compounds unite by addition with 
 sulphurous acid or bisulphites; as commercial sodium hydrosul- 
 phite always reeks with sulphur dioxide, the immediate forma- 
 tion of the addition-product Ar.NH.CH 2 .SO 3 H seems probable. 
 Reduction of such compounds to Ar.NH.CH 3 by hydrosulphite 
 could hardly be expected. 
 
 Attempted reductions of methyl ene-p-aminophenol by means 
 of sodium hydrosulphite yielded no secondary amine, but a readily 
 soluble yellow-white crystalline substance which evolved sulphur 
 dioxide when warmed with acids. 
 65 Zeit. eleciroch., 4, 428 (1897/8). 
 Ib., 9,470 (1903)- 
 
 17 
 
METHYIvATlON OF PARA-AMINOPHENOI, 
 
 (2) Reduction of the Exochlormethylanilines, formed by 
 Acid Condensation 
 
 Only a single intance has been found in which such a reduction 
 is reported. Goldschmidt 67 reduced N-methyleneaniline (an- 
 hydroformaniline) with tin and hydrochloric acid, condensed 
 the resulting methylaniline with formaldehyde, and then reduced 
 
 the resulting C 6 H 5 .N<;;J?* . with tin and hydrochloric acid, 
 v~xl,L,l 
 
 obtaining dimethylaniline. 
 
 A prolonged attempt to duplicate the second reduction, using 
 tin and hydrochloric acid at ioo, was without effect upon the 
 exochlor-compound. Similar experiments were carried out 
 with p-amino-phenol, which was condensed with formaldehyde 
 in presence of hydrochloric or sulphuric acid in varying amounts. 
 The product was subjected to reduction by various means, but 
 in no case could the presence of secondary amine be detected. 
 (5) Reduction of the Bisulphite Addition-products of the 
 
 Anhydro formaldehyde-bases 
 
 As a means for testing the possibility of effecting the change 
 Ar.NH.CH 2 .SO 3 H - Ar.NH.CH 3 + HSO 3 Na, the bisulphite 
 addition-product of methyleneaniline was prepared from formal- 
 dehyde-bisulphite and aniline, 68 and was reduced by tin or zinc 
 and hydrochloric acid. In both cases free sulphur was separated, 
 but steam-distillation of the alkalized liquid yielded no volatile 
 product. The possibility of splitting off the -SO 3 H group hydro- 
 lytically was also studied, but positive results were not obtained. 
 (4) Hydrolysis of the Hydrocyanic Acid Addition-pro- 
 ducts of the Anhydr of ormaldehy de-Bases, and Elimina- 
 tion of Carbon Dioxide by Heat 
 
 The decarboxylation of p-hydroxy-phenyglycine was suggested 
 by Paul 69 as a method for preparation of methyl-p-aminophenol. 
 Trial of this method by Harger 70 gave poor results, and led him 
 to a further study of the method of Merck and Co., using hydro- 
 87 Chent. Ztg., 28, 1229 (1904). 
 68 Orloff, /. ., p. 37. 
 * Zeit. angcw. Ch. 10, 17 (1897). 
 70 /. A. <T. S., 41, 270 (1919). 
 
 iS 
 
METHYLAT1ON OF PARA-AMINOPHENOL 
 
 quinone and methylamine. 71 The writer made no trial of Paul's 
 method. 
 
 III. Experimental Results on the Methy lation of p-Aminophenol 
 by Means of Formaldehyde. 
 
 Results by methods (2) and (3) (see page 14) will be given 
 briefly first. Method (4) was not subjected to trial, and need 
 not be referred to again. Method (i), on which numerous ex- 
 periments were made, will be considered last. 
 
 Reduction of Exochlormethyl-p-aminophenol, 
 
 HO.C 6 H 4 .NH.CH 2 Cl 
 
 According to the general reaction given on page 12 (d), p- 
 aminophenol would react with formaldehyde in hydrochloric acid 
 solution as follows : 
 
 HO.C 6 H 4 .NH;H. HjCl + : O ;CH, 
 
 HO.C 6 H 4 .NH.CH 1 C1 + HO. 
 ( exochlormethy 1-p-aminophenol ) 
 
 The condensation-product loses hydrochloric acid under the in- 
 fluence of alkali (sodium carbonate), and is converted into 
 
 NH 
 
 hydroxy-anhydro-aminobenzylalcohol, HO.C 6 H 3 < i which 
 
 CH 2 
 
 is insoluble in water. The instability of the exochlor-compound 
 in presence of alkali must be borne in mind in selecting a method 
 for its reduction. Alkaline reduction is excluded, as the an- 
 hydrobenzylalcohol-derivative would form at once, and on reduc- 
 tion would yield an oxytoluidine. 72 Acid reduction, after the 
 anhydroaminobenzylalcohol is once formed, is also inadmissible, 
 as this compound, when dissolved in dilute acids, does not re- 
 vert to the exochlor-compound, but, by virtue of its character as 
 a secondary amine, forms a salt. 
 
 For the preparation of exochlormethyl-p-aminophenol, recourse 
 was had to the method of Goldschmidt, 73 and to several patented 
 
 71 D. R. P. 260234; A. P. 1297685 (Harger). 
 
 " D. R. P. 83544. 
 
 Chtm. Ztg., 24, 284 (1900). 
 
 19 
 
METHYIvATlON OF PARA-AMINOPHENOI, 
 
 processes. 74 The last-mentioned patent deals with the condensa- 
 tion of formaldehyde with para-substituted aromatic bases (not 
 p-aminophenol), and seems therefore to be especially relevant, 
 though it is the alkali transformation-products of the exochlor- 
 compounds the preparation of which is there described. The 
 exochlor-compounds formed remain for the most part in solu- 
 tion. This is the case also when the simple primary aromatic 
 amines are condensed with formaldehyde in dilute acid solution, 
 but contrasts with the behavior of the secondary amines, the ex- 
 ochlormethyl-derivatives of which are precipitated by hydro- 
 chloric acid, though soluble in water. 75 
 
 Isolation of the compound HO.C 6 H 4 .NH.CH 2 C1, obtained from 
 HO.C 6 H 4 .NH 2 .HC1 and formaldehyde, was undertaken in a 
 number of experiments, in which the acidity ranged from that of 
 the p-amino-phenol hydrochloride itself to that produced by ad- 
 dition of about an equal volume of concentrated hydrochloric acid 
 to the solution. Sulphuric and acetic acids also were used. The 
 solid product of such condensations was in general scanty, dark 
 brown in color, and amorphous ; it frequently separated in coher- 
 ent and glue-like masses. Only at the higher concentrations of 
 acid was there a reasonably copious separation of solid material. 
 Thus, using 20 grams of p-aminophenol hydrochloride in 90 cc. 
 of water, 25 grams of 38 per cent formaldehyde (more than two 
 equivalents), and 95 cc. of concentrated hydrochloric acid, and 
 allowing condensation to proceed in the cold overnight, only a 
 small amount of material separated. After heating for some 
 time on the water-bath, a dark brown powder and some lumps 
 separated on chilling. When dried, this material weighed 14 
 grams, a yield of 64 per cent, assuming it to be the compound 
 HO.C 6 H 4 .NH.CH 2 C1. It was found to be soluble in hot water, 
 from which it separated in muddy form on chilling, though with 
 considerable loss. The aqueous solution was precipitated by the 
 common acids; sodium carbonate solution produced a flocculent 
 precipitate; the material dissolved very readily in caustic soda. 
 The "recrystallized" material dried to a rather brittle, resinous 
 
 74 D. R. P. 96851, 97710, 122474. 
 
 T5 Goldschmidt, Chem. Ztg. 1. c.\ Id., 26, 606 (1902); D. R. P. 97710. 
 
 20 
 
METHYI<ATION OF PARA-AMINOPHENOi, 
 
 mass, yielding when ground a chocolate-brown powder. It re- 
 sponded positively for chlorine both to the copper-wire test, and 
 to silver nitrate in water solution. The latter may be taken as 
 an indication of impurity. 76 The same conclusion was reached 
 by analysis for nitrogen (Kjeldahl), 7.9 per cent being found, 
 instead of 8.9 per cent as required by the formula. When con- 
 densation was carried out in larger volumes, and with less acid 
 present, practically no precipitate appeared. In all these con- 
 densations the liquid became deep red in color. 
 
 Reduction of such solutions with zinc-dust, or with tin, 77 by 
 sodium amalgam (keeping the solution slightly acid), by sodium 
 hydrosulphite, or by electrolysis in sulphuric acid solution, yielded 
 no secondary amine separable as nitrosamine. Similar results 
 were obtained using the isolated condensation-product. 
 
 Reduction of the Bisulphite Addition-product of Methylene- 
 
 p-amino phenol 
 
 The additive union of sulphurous acid and its salts with for- 
 maldehyde condensation-products of the aromatic amines was 
 studied by Eibner. 78 The formation of the compound 
 HO.C 6 H 4 .NH.CH 2 .SO 3 Na, or (HO.C 6 H 4 .N:CH 2 )NaHSO 3 , is 
 the subject of D. R. P. 68707 : p-aminophenol is condensed with 
 formaldehyde in alkaline solution, the product is precipitated by 
 carbon dioxide, dissolved promptly in sodium bisulphite solution, 
 and the addition-product obtained by crystallization. The bisul- 
 phite compound is very soluble in water, and crystallizes as small 
 nearly white plates. This compound can be very conveniently 
 prepared by addition of solid p-aminophenol to a hot concentrated 
 solution of formaldehyde bisulphite. The base passes into solu- 
 tion; when chilled, the liquid sets to a mass of crystals. A 
 fairly strong solution of this product, when acidified with sul- 
 phuric or hydrochloric acid, separated small glistening crystals, 
 much less soluble in water than the original compound, but readily 
 soluble in alkali. Hot dilute sulphuric acid liberated sulphur 
 dioxide; the odor of formaldehyde was noticed also. It seems 
 T D. R. P. 96851. 
 
 " Goldschmidt, Chem. Ztg. 28, 1229 (1904). 
 78 Annal., 316, 89 (1901). 
 
 21 
 
MSTHYI.ATION OF PARA-AMINOPHENOI, 
 
 that this compound is the free acid HO.C 6 H 4 .NH.CH 2 .SO 3 H. 
 Eibner 79 reported an analogous behavior of the corresponding 
 aniline compound. 
 
 Efforts to convert the compound HO.C 6 H 4 .NH.CH 2 .SO 3 Na 
 into HO.C 6 H 4 .NH.CH 3 were referred to on page 18. 
 
 Hydrogenation of N-Methylene-p-aminophenol, (HO.C 6 H 4 .N:CH 2 ) n 
 
 Experiments included under the above heading constitute the 
 chief experimental basis of this paper, and will be described with 
 more detail than was thought desirable for other methods. The 
 principal operations in all of the methods to be described are 
 
 (1) Condensation of p-aminophenol and formaldehyde in al- 
 kaline solution. 
 
 (2) Reduction of the condensation-product. 
 
 (3) Isolation of the methylated base 
 
 (i) Condensation of p-Aminophenol and Formaldehyde in 
 Alkaline Solution 
 
 According to the directions of D. R. P. 68707, p-aminophenol 
 is dissolved in water (21 grams per liter), the solution filtered, 
 chilled to 5 io, and treated with somewhat more than one 
 equivalent each of sodium hydroxide and formaldehyde. The 
 solution is allowed to stand several hours, and the condensation- 
 product, present in solution as the phenolate, is precipitated by 
 conducting carbon dioxide into the liquid, or by addition of soda. 
 The liquid always possesses a strong and offensive "fishy" odor, 
 and darkens promptly when exposed to air. The precipitated 
 methylene-base is generally flocculent, and light in color, with 
 often a pinkish cast. If incorrectly precipitated, it may appear 
 in the form of large coherent lumps. 
 
 The condensation-product is insoluble in water, ether, or ben- 
 zene; it is soluble in alcohol, readily soluble in alkali, the solu- 
 tion thus obtained having the properties, as regards odor and 
 air-oxidation, of the original condensation-liquid; the alkaline 
 solution reduces silver salts. The condensation-product is pre- 
 cipitated from alkaline solution by addition of acids, but the 
 79 /. c. 
 
 22 
 
METHYLATION OF PARA-AMINOPHENOI, 
 
 precipitate dissolves in a sufficient excess of the acid: the odor 
 of formaldehyde can then be detected, indicating hydrolysis of 
 the methylene-base. When dried in air, methylene-p-aminophenol 
 darkens somewhat, as a result of polymerization, and probably 
 of oxidation. 
 
 It was found convenient to use p-aminophenol hydrochloride 
 instead of the free base, because of the greater stability and solu- 
 bility of the former. Most of the material used was the East- 
 man product. It contained 1.39 per cent of inorganic material 
 (ash), and 0.12 per cent moisture. Early experiments were made 
 using Kahlbaum's p-amino-phenol hydrochloride, and some others 
 using material prepared electrolytically by Dr. H. S. Lukens. 
 
 For the purification of p-aminophenol hydrochloride advantage 
 was taken of the fact that this salt is precipitated almost com- 
 pletely when its strong solution, externally cooled, is saturated 
 with gaseous hydrochloric acid. To obtain the free base for im- 
 mediate use, a concentrated solution of the hydrochloride, cooled 
 to about o, was treated with strong sodium carbonate solution 
 until effervescence ceased. The base separated in granular form, 
 and was filtered off and pressed. The yield by this method is 
 good, the solubility of the base at o being about I part per 100 
 of water. The product contains alkali, and cannot be dried or 
 kept. To prepare p-aminophenol in stable form, it is advisable to 
 crystallize it from hot water containing bisulphite, and to wash it 
 with cold bisulphite solution. 
 
 To study the condensation quantitatively, the methylene-base, 
 after formation under the selected conditions, was precipitated 
 from the properly diluted solution, washed with water, dried care- 
 fully, and weighed. The procedure for the isolation is given later. 
 In some of the later experiments the uncondensed p-aminophenol 
 was precipitated from the filtrate in the form of its benzylidine- 
 derivative. The latter is precipitated 80 by shaking the solution, 
 acidified with acetic acid, with benzaldehyde. The product is 
 washed with water, dried, and weighed. 
 
 The results obtained under various conditions of condensation 
 appear in Table I. 
 
 10 Haegele, Ber., 25, 2753 (1892); Cf. Michaelis, Per., 27, 3005 (1894) 
 
 23 
 
I 
 
 . g 
 M -a 
 
 SI 
 
 $$& 
 
 (>4 * 
 
 
 
 
 
 
 
 
 
 
 
 s 
 
 g 
 
 1 
 
 s 
 
 **i 
 
 ^'8 
 
 fc 
 
 
 
 
 
 
 
 
 
 
 
 a 
 
 N 
 
 s 
 
 01 
 
 Benzal- 
 comp. 
 from 
 filt. 
 
 
 
 
 
 
 
 
 
 
 
 o 
 
 ^ 
 
 oo 
 M 
 
 fh 
 
 tj- 
 
 ^ 
 
 2 
 M^JLJ 
 
 5? 
 
 R 
 
 8 
 
 s 
 
 g 
 
 S 
 
 S 
 
 S 
 
 S 
 
 
 
 s 
 
 5 
 
 J: 
 
 R 
 
 j: 
 
 tfii 
 
 
 
 
 
 
 
 
 
 
 
 
 o 
 
 ^o 
 
 
 
 q 
 
 c< 
 
 o8& 
 
 
 
 
 
 
 
 t^ 
 
 10 
 
 t^. 
 
 
 tO 
 
 vb 
 
 VO 
 
 ro 
 
 
 b 
 
 
 
 
 
 
 b 
 
 
 
 h 
 
 
 
 
 
 
 ^ 3 
 
 1*1 
 
 2 fc 
 
 "S 3 
 
 c a 
 2 
 
 
 
 
 
 K 
 
 ^5 
 
 "3 
 a 
 
 
 1 
 
 1 
 
 ^^3 
 <u s 
 
 a n 
 
 ss 
 
 
 
 
 
 
 
 M 
 
 
 
 
 
 
 O 
 
 H 
 
 bo 
 
 
 
 
 
 
 
 
 o 1 
 
 
 
 8-s 
 
 : 
 
 : 
 
 5 
 
 : 
 
 J 
 
 u 
 i 
 
 n 
 
 o 
 o^^ 
 ^0 
 
 M 
 
 0-d^ 
 ^ ^ 
 
 ! 
 
 - ' 
 
 s 
 
 : 
 
 1 
 
 t.& 
 
 8 g 
 
 I s 
 
 
 
 
 
 5 
 
 s 
 
 ; 
 
 J3.2 
 o-d 
 
 tfl^'S. 
 a cs 2 
 
 W^ 
 
 (JO!* 
 >. 
 
 
 
 
 
 
 a, 
 
 
 
 
 
 
 
 
 ^ 
 
 ft 
 
 * 
 
 ** 
 
 * 
 
 " 
 
 
 
 8 j| 
 
 >o 
 
 10 
 
 10 
 
 m 
 
 
 
 
 
 
 
 
 
 
 
 H * 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 1 8 
 
 g 
 
 
 _o 
 
 
 
 |.Sl 
 
 s B 
 
 ^1 
 
 = 38 
 
 & 
 
 8 
 
 5 
 
 i 
 
 a 
 
 1 3 
 
 "? 
 
 m 
 
 "? 
 
 10 
 
 ir> D 
 
 , 
 
 "? 
 
 IT. 
 
 10 
 
 lO 
 
 IO 
 
 u-> 
 
 ID 
 
 " 
 
 1 
 
 
 
 
 
 M 
 H 
 
 
 
 
 
 
 
 
 
 
 S~B 
 
 s*i 
 
 .& 
 "i 
 
 o 
 
 
 5 
 
 o 
 
 N 4; 
 
 M v 
 
 q 
 
 vO 
 
 
 
 vd 
 
 
 
 a 
 
 
 ip 
 
 3 
 
 o 
 
 
 
 
 Ifi 
 
 
 -0 
 
 
 
 
 
 
 
 fO 
 
 *' 
 
 j & 
 
 
 
 
 
 o 
 
 2 
 
 O 
 
 
 
 o 
 
 o 
 
 
 
 
 
 
 
 
 
 2 
 
 i 
 
METHYtATlON OF PARA-AMINOPHENOI, 
 
 The data just given seem to justify the following conclusions : 
 
 (1) The extent of the condensation is relatively independent 
 of experimental conditions, provided that there are present at least 
 one equivalent of formaldehyde, and two equivalents of sodium 
 hydroxide, for each equivalent of p-aminophenol hydrochloride 
 (or one equivalent of sodium hydroxide if free p-aminophenol 
 is used). Excess of formaldehyde or of sodium hydroxide is 
 without apparent effect. 
 
 (2) Low temperature favors slightly increased condensation, 
 as shown by the sixth, seventh, and ninth experiments, in com- 
 parison with other trials, which were conducted at 15 20. 
 
 (3) Condensation is not increased by prolongation of the 
 time beyond two hours. As shown by experiments not listed 
 above, over-night condensations tend to yield a denser and darker 
 product, with no advantage in the matter of yield or of ease of 
 reduction. 
 
 (4) The volume in which condensation occurs is almost with- 
 out effect. The only definite exception to this statement is pre- 
 sented by the thirteenth experiment, in which the volume was 
 relatively large, the result being that normal condensation was 
 not quite complete at the end of two hours. 
 
 (5) The last four experiments indicate that practically all 
 the p-aminophenol hydrochloride taken initially is accounted for, 
 either as methylene-p-aminophenol or as the uncondensed base. 
 
 (6) Condensation of formaldehyde and p-aminophenol occurs 
 to the extent of about 75 to 85 per cent. 
 
 The experiments recorded above, together with many inciden- 
 tal observations made during the course of the work, led to the 
 adoption of the following 
 
 Procedure for Condensation of Formaldehyde and p-Amino- 
 
 phenol 
 
 (a) Condensation Dissolve 10 parts of p-aminophenol hydro- 
 chloride in about 60 parts of water, and filter the solution. 
 Transfer the nitrate to a flask, and chill well under the tap, or 
 better in ice. Add at one time one-half of a solution which con- 
 tains 7.5 parts (somewhat more than two equivalents) of sodium 
 
MET HYI^ATION OF PARA-AMINOPH^NOI, 
 
 hydroxide, and cool until the heat of neutralization is absorbed. 
 Now add the remaining sodium hydroxide, which will dissolve 
 the precipitated p-aminophenol. To the cold alkaline solution add 
 6 parts of 38 per cent formaldehyde (somewhat more than one 
 equivalent) gradually, with rotation of the flask. Insert a stopper, 
 and keep the flask in a cool place for two or three hours. 
 
 (b) Isolation Pour the liquid into a large beaker or jar con- 
 taining cold water, and provided with an efficient mechanical 
 stirrer, and, appropriately supported above the precipitating 
 vessel, a separatory funnel containing 30 per cent acetic acid. 
 The volume at the time of precipitation should be rather large, 
 or the liquid will become so filled with the precipitated product as 
 to interfere with effective stirring. A volume somewhat greater 
 than 500 cc. is convenient for precipitation of the condensation- 
 product from 10-15 grams of p-aminophenol hydrochloride. With 
 the stirrer in motion, allow 30 per cent acetic acid to drop into 
 the liquid, until the reaction is distinctly acid to litmus. The 
 condensation-product will be precipitated in a finely granular 
 form which settles promptly and is easily filtered and washed. 
 Filter off the product on a Biichner funnel, wash with cold water, 
 press down well with a spatula, and dry the material as far as 
 possible by suction. Transfer it to a watch-glass or plate, and 
 keep in a slightly warm place for several hours, with occasional 
 reduction of lumps as drying progresses. Dry finally at 8o-9O. 
 The product is thus obtained as a loose, soft, grayish powder, 
 which assumes a brown color after long exposure to the air. If 
 the drying is done too rapidly, the condensation-product may 
 become resinous. 
 
 Precipitation by carbon dioxide gives equally good results, but 
 is less rapid and less convenient; the use of sodium bicarbonate 
 solution for the precipitation occasionally caused the separation 
 of a coherent product. 
 
 When reduction of the methyl ene-p-aminophenol is intended, 
 it should be used shortly after precipitation, and without drying, 
 as the completely dried product is reduced with difficulty. As 
 will appear below, isolation of the condensation-product is not 
 essential, and is quite properly omitted. 
 
 26 
 
METHYLATION OF PARA-AMINOPH^NOIy 
 
 Before the reduction of methylene-p-aminophenol is discussed, 
 it is necessary to describe the methods of forming and handling 
 the nitrosamine of N-methyl-p-aminophenol, since it is in this form 
 that the reduction-product can be most readily and completely 
 isolated, and the effectiveness of the reduction determined. 
 
 p-Hydroxy-methylphenylnitrosamine, 
 
 This compound is obtained by the usual procedure for nitro- 
 samine formation: addition of sodium nitrite solution to the 
 chilled acidified solution of the secondary amine. It separates 
 from solution in crystalline form, the color of the crystals de- 
 pending upon the presence of impurities in the solution. The 
 pure secondary base yields nearly white, or gray, minute needles, 
 having a low solubility in cold water. When precipitation is 
 effected from solution containing p-aminophenol, formation of 
 the nitrosamine is noticeably delayed, due no doubt to the superior 
 reactivity of the primary base. In such cases, also, tar- formation 
 is almost invariable, and the nitrosamine separates as brown 
 granular crystals. Under unfavorable conditions the separation 
 of tar has been considerable, rendering purification of the nitro- 
 samine, without considerable loss, impossible. 
 
 The nitrosamine is a somewhat unstable compound, and suf- 
 fers serious decomposition, with darkening, if an attempt is 
 made to dry it while moist with any trace of the acid mother- 
 liquor, or to crystallize it from strong alcohol ; less extensive de- 
 composition occurs if dilute alcohol is used. Rather oddly, the 
 compound seems to be most satisfactorily crystallized from hot 
 water, in which it is moderately soluble. For this purpose, the 
 nitrosamine is suspended in water (about 50 cc. for each 3 
 grams), the mixture heated nearly to boiling, and about 5 cc. of 
 alcohol added. Solution is completed without unnecessary heat- 
 ing, and the liquid is cooled in ice. The nitrosamine crystallizes 
 out rapidly, and with nearly quantitative completeness. 
 
 For purposes of comparison, 2.0 grams of Metol (Hauff) were 
 dissolved in 200 cc. of water, 10 cc. of strong hydrochloric acid 
 added, and the solution cooled in an ice-bath. It was then 
 treated dropwise with a 20 per cent solution of sodium nitrite, 
 
 27 
 
METHYLATION OF PARA-AMINOPHENOL 
 
 until a drop of the liquid, applied to potassium iodide paper, 
 showed presence of nitrous acid in excess. The nitrosamine 
 separated, during the addition of nitrite, as minute almost white 
 needles, which were filtered off, and washed sparingly with cold 
 water. After several recrystallizations from dilute alcohol, the 
 nitrosamine was obtained as fairly large flat needles, slightly 
 straw-tinged, and melting at 134.3 (corr.), with decomposition 
 above the melting temperature. In regard to the melting-point 
 of the nitrosamine, it should be added that Clarke 81 gives 136, 
 a value never obtained by the writer. 
 
 An interesting behavior was observed when an excess of 
 nitrous acid was allowed to act upon the precipitated nitrosamine. 
 There was obtained a bright yellow insoluble powder, which 
 melted with decomposition at I26-I27, with previous softening. 
 The bottle in which this material was kept was gradually colored 
 a bright red on its entire inner surface. The reaction recalls the 
 simultaneous nitrosation and nitration of methylaniline by means 
 of nitrogen dioxide, as described by Stoermer. 82 
 
 Finally, it is of interest to consider the formation of the nitro- 
 samine as an identification test for N-methyl-p-aminophenol. 
 Attention may be called to the mercuric acetate test described by 
 Harger 83 which is said to disclose the presence of metol in a con- 
 centration of i :iooooo by the gradual development of a grape- 
 juice color. The nitrosamine test is by no means so delicate as 
 this, but is more characteristic. It appears that the mercuric 
 acetate test is not entirely specific, since a by-product was 
 obtained, by ether extraction of the alkalized solution after 
 reduction of methylene-p-aminophenol, which was obviously not 
 methyl-p-aminophenol (its sulphate was excessively soluble in 
 water), but which responded to the mercuric acetate test more 
 strongly than "metol" itself. The color developed was nearly blue, 
 but in cases of doubt would certainly cause confusion. 
 
 To test a material for presence of a salt of methyl-p-amino- 
 phenol, a little of the substance is dissolved in a small volume of 
 
 81 /. Ind. Eng. Chem., 10, 891 (1918). 
 
 82 Arr., 31,2523 (1898). 
 
 /. A. C. 5., 41, 270 (1919). 
 
 28 
 
METHYLATION OF PARA-AMINOPHENOI, 
 
 water, the solution acidified with a drop or two of hydrochloric 
 acid, chilled, and sodium nitrite solution added in slight excess. 
 A precipitate of minute needles, which usually appears suddenly, 
 and which seems to fill the liquid, constitutes a positive test. If 
 this material is recrystallized from a little water containing* 
 alcohol, and its melting-point determined, the identification of 
 methyl-p-aminophenol may be regarded as certain. Identification 
 by means of the sulphate or the dibenzoyl-compound is less con- 
 venient, as these derivatives are less characteristic in appearance, 
 and have higher melting-points. 
 
 (2) Reduction of N-Methylene-p-aminophenol to N-Methyl- 
 p-aminophenol- 
 
 Reference to page 15 shows the investigated methods 
 of reduction to be the following: 
 
 (a) Reduction by Sodium Amalgam, or Metallic Sodium, and 
 Alcohol. 
 
 (b) Reduction by Zinc-dust and Alkali. 
 
 (c) Reduction by Zinc-dust and Acid. 
 
 (d) Reduction Electrolytically in Alkaline Solution. 
 
 (e) Reduction Electrolytically in Acid Solution. 
 
 (f) Reduction Electrolytically of p-Nitrol-phenol or p- 
 Nitroso-phenol in presence of Formaldehyde. 
 
 (g) Reduction by Hydrosulphite. 
 
 In all cases the success of the reduction was tested by means 
 of the nitrosamine reaction. Of the above methods, only method 
 (c) yielded positive results which were uniformly reproducible. 
 Method (e) was attended with some success, and would possibly 
 repay closer study. The other methods were apparently quite 
 unsuccessful, and may be disposed of rather briefly. 
 
 (a) Reduction by Sodium Amalgam, or by Sodium, and 
 Absolute Alcohol Both aqueous (acid or alkaline) 
 solutions of the condensation-product, and alcoholic solutions, 
 were subjected to action of sodium amalgam. Reduction by 
 metallic sodium was applied to the solution of methlyene-p- 
 aminophenol in anhydrous ethyl alcohol. In neither case could 
 
 29 
 
METHYLATION OF PARA-AMINOPHENOI, 
 
 presence of secondary amine be detected in the liquids, after 
 suitable preparation for precipitation of nitrosamine. 
 
 (b) Reduction by Zinc-dust and Sodium Hydroxide 
 
 This method was applied to the reduction of benzylidene- 
 p- aminophenol and of methylene-p-aminophenol, obtained from 
 p-aminophenol by condensation with, respectively, benzaldehyde 
 and formaldehyde. It was expected that these compounds would 
 behave similarly upon reduction; their chemical similarity is 
 shown by the formulas HO.C 6 H 4 .N :CH.C 6 H 5 and 
 HO.C 6 H 4 .N:CH 2 . 
 
 Reduction of benzylidine-p-aminophenol 84 was quite success- 
 ful : 17 grams of this compound gave 18 grams of benzyl-p- 
 aminophenol hydrochloride, a yield of 89 per cent. The base was 
 found to melt at 87-88 ; the nitrosamine, crystallized from 
 dilute alcohol, melted at 142.5 (corr.). A picrate was prepared, 
 as large bright yellow irregular prisms, very sparingly soluble in 
 water, and melted at i66-i67 (corr.). It should be noted that 
 the melting-point of the nitrosamine is given 85 as 148. 
 
 The same procedure, as well as that of A. P. 1221077, w ^h 
 varying temperatures, concentrations of alkali, and proportions 
 of base and formaldehyde, when applied to the reduction of 
 methylene-p-aminophenol, failed to produce any methyl-p-amino- 
 phenol which could be separated as nitrosamine. 
 
 (c) Reduction by Zinc-dust and Acid This method will be 
 discussed in some detail below. 
 
 (d) Reduction Electrolytically in Alkaline Medium 
 
 As a test of the method, the benzylidine-p-aminophenol obtained 
 from 22 grams of p-aminophenol hydrochloride and 16 grams of 
 benzaldehyde was dissolved in 12 per cent sodium hydroxide 
 solution, and subjected to reduction using iron electrodes. 
 Absorption of hydrogen was very imperfect. A current of about 
 5 amperes (cathode area about 220 cm. 2 was continued for 3.5 
 hours, with continuous evolution of unabsorbed hydrogen. The 
 liquid was finally acidified with sulphuric acid, filtered, and 
 
 84 D. R. P. 211869. 
 
 85 Zeit.electroch., 18, 745. 
 
 30 
 
METHYLATION OF PARA-AMINOPHENOI, 
 
 chilled, when 2 grams of the difficulty soluble benzyl-p-amino- 
 phenol sulphate separated. The nitrosamine of this product 
 melted at 142 (see page 30). 
 
 The same procedure was applied for the reduction of methy- 
 lene-p-aminophenol dissolved in 15 per cent sodium hydroxide 
 solution. There was no apparent absorption of hydrogen, and no 
 methylated product was detected in the liquid after reduction. 
 (e) Reduction Electrolytically in Acid Solution 
 The electrolytic cells used in all reductions recorded in this 
 paper were identical in design with the cell devised by Dr. H. S. 
 Lukens, whose description of it is now awaiting publication. 
 Cells of three sizes were used, having capacities of 500 cc., 250 
 cc., and 100 cc. The last mentioned was used for reductions cit 
 lower temperatures. The porous cup of this cell was closed by 
 a large rubber stopper 86 which served as a support for the lead 
 electrode, the liquid seal of the stirrer, the vent-tube, and an in- 
 
 TABLE II. 
 
 Electrolytic Reductions 
 
 
 
 
 
 
 
 
 Nitros- 
 
 
 P. A. P. 
 
 gms. 
 
 Method of preparation 
 for electrolysis 
 
 Amp. 
 
 Volt 
 
 Temp. 
 
 Time 
 hrs. 
 
 Gas 
 
 amine 
 gms. 
 
 f 
 
 Yield 
 
 12.5 
 
 Condensed overnight. 
 Poured into equal 
 
 10 
 
 4 
 
 - 
 
 6 
 
 None 
 at first 
 
 I.O 
 
 8 
 
 
 vol. 40 H 2 SO 4 
 
 
 
 
 
 
 
 
 25 
 
 Condensed 36 hours. 
 
 5-5- 
 
 4 
 
 
 
 3 
 
 H- 
 
 + 
 
 
 
 Added to equal vol. 
 
 7 
 
 
 
 
 after 
 
 
 
 
 80 $ H 2 SO 4 
 
 
 
 
 
 i hr. 
 
 
 
 12.5 
 
 Condensed 2 hours. 
 
 2 
 
 3-5 
 
 
 
 3-5 
 
 
 O.2 
 
 1.6 
 
 
 Ppted, byCH 3 COOH; 
 dissolved in 45 gms. 
 
 
 
 
 
 + 
 from 
 
 
 
 
 25 <p H 2 SO 4 , added 40 
 cc. 8056 H 2 SO 4 . 
 
 
 
 
 
 start 
 
 
 
 
 Small cell 
 
 
 
 
 
 
 
 
 12.5 
 
 Condensed overnight; 
 ppted. by CO.>; dis- 
 
 2 
 
 4 
 
 5- 
 9 
 
 5 
 
 + 
 
 2-4 
 
 18 
 
 
 solved in 90 cc. 40 # 
 
 
 
 
 
 after 
 
 
 
 
 H 2 SO 4 at 5. 
 
 
 
 
 
 ihr. 
 
 
 
 
 Small cell 
 
 
 
 
 
 
 
 
 12.5 
 
 Condensed 2 hours; 
 ppted. by CH 3 COOH; 
 dissolved in 200 cc. 
 
 IO-II 
 
 6-7 
 
 not 
 cooled 
 
 4 
 
 little 
 for 
 i hr 
 
 I.O 
 
 8 
 
 
 20 alcoholic H 2 SO 4 
 
 
 
 
 
 then + 
 
 
 
 86 Tafel, Ber. t 33, 2209 (1900.) 
 
METHYIvATlON OF PARA-AMINOPHENOL 
 
 serted thermometer. The electrodes of these cells were made of 
 commercial lead. 
 
 Results of some of the electrolytic reductions are tabulated 
 above. The temperature, during addition of acid to condensa- 
 tion-product (either isolated or in solution) was kept low 87 so 
 as to avoid hydrolysis of the condensation-product. 
 
 A number of experiments not listed above were entirely with- 
 out positive result. The effect of amalgamating the cathode, or 
 of using very pure lead, was not investigated. In the last ex- 
 periment, an aliquot portion was examined, after reduction, for 
 unchanged p-aminophenol : 37.5 per cent of that initially taken 
 was recovered. 
 
 (f) Electrolytic Reduction of p-Nitrophenol or of p-Nitroso- 
 phenol in Presence of Formaldehyde 
 
 Reference may be made to the statements which appear under 
 the same heading on page 17. 
 
 The reduction of 15 grams of p-nitrophenol in alcohol-hydro- 
 chloric acid solution, in presence of 10 grams of 38 per cent for- 
 maldehyde (about one equivalent), absorbed the hydrogen from 
 a current of 10 amperes for over an hour. Electrolysis was con- 
 tinued for nearly five hours, when evolution of unabsorbed gas 
 was rapid. The clear red liquid was distilled free from alcohol, 
 made alkaline with sodium carbonate, filtered, and extracted with 
 ether. During distillation of the ether, a quantity of small 
 crystalline plates separated. These were removed (1.4 gram), 
 and were identified as p-aminophenol [m. p., i83-i85; m. p. of 
 benzylidine-derivative, 185]. The solid material precipitated 
 by sodium carbonate was dissolved in dilute hydrochloric acid, 
 boiled with charcoal, filtered, and the solution precipitated by 
 sodium acetate. A white amorphous material, weighing 2.2 
 grams, was obtained. This product seems to correspond to the 
 by-product obtained by Lob and by Goecke during the electro- 
 lytic reduction of p-nitrotoluene in presence of formaldehyde, 
 and is possibly an anhydroamino-oxy-benzyl alcohol. 
 
 The oil left after evaporation of the ether was subjected to 
 vacuum distillation. At 18 mm., distillation began at 162, and 
 87 D. R. P. 143197- 
 
 32 
 
METHYI^TION OF PARA-AMINOPHENOI, 
 
 was continued up to 175 (25 mm.). The product was a dark 
 brown, viscous oil, which could not be solidified ; its amount was 
 too small to warrant purification. The data from the distilla- 
 tion furnish some basis for the belief that dimethyl-p-amino- 
 phenol (b. p. 30 = 162) was present. 
 
 A number of similar reductions of p-nitro-phenol and of 
 p-nitrosophenol were carried out in presence of formaldehyde, 
 but in no case could any secondary base be isolated after re- 
 duction. This method seems to serve only for the formation of 
 dimethylanilines from the corresponding nitro- or nitroso-com- 
 pounds ; mono-methylation apparently does not occur. 
 
 (g) Reduction by Sodium Hydro sulphite- 
 No addition need be made to the remark on page 17. 
 
 (c) Reduction of N-Methylene-p-aminophenol to N-Methyl-p- 
 
 aminophenol by Zinc-dust and Acid- 
 After a number of preliminary trials, evidence of methylation, 
 by zinc-dust and dilute hydrochloric acid, was first obtained by 
 isolation of a benzoyl-compound melting at 172- 177 (m. p. 
 dibenzoyl-methyl-p-aminophenol = 174)- By a similar pro- 
 cedure, using sulphuric acid, a nitrosamine melting at I33-I34 
 was obtained, identical with that from metol. It was found that 
 reduction by zinc and acid could be effected either with or with- 
 out isolation of the condensation- product HO.C 6 H 4 .N :CH 2 . The 
 yields were always small, however, a fact at first attributed to 
 the decomposition of the methylene-p-aminophenol by hydrolysis. 
 Data to be given later will show that this hydrolysis is by no 
 means so considerable as was thought. 
 
 The conditions by variation of which the reduction might be 
 expected to be influenced are rather numerous; experiment has 
 shown, however, that the process is actually rather unresponsive 
 to modifications in conditions. The opinion is held at present 
 that the small extent of the methylation is due in large part to 
 a side-reaction of the same kind as that which diminished to about 
 40 per cent the yields in Lob's and in Goecke's electrolytic reduc- 
 tions referred to previously. There seems to be reason to be- 
 
 33 
 
METHYI,ATION OF PARA-AMINOPHEJNOL 
 
 lieve that this side-reaction is only the normal action of acid 
 upon the formaldehyde condensation-product, as shown on page 
 8. 
 
 Results of a number of experiments will now be tabulated, 
 showing the influence of various conditions upon the reduction. 
 It is to be emphasized that the yields set down in Tables III, IV, 
 and V, neglect the recoverable p-aminophenol present after re- 
 duction, and are calculated on the basis of total p-aminophenol 
 taken initially and that finally obtained in the methylated form 
 (as nitrosamine). These yields are therefore given too low by 
 about 10 per cent. 
 
 TABLE III. 
 
 Experiments to determine 
 
 (a) Relative values of several methods for precipitating 
 condensation-product. 
 
 (b) Necessity for isolation of condensation-product. 
 
 P. A. P. 
 
 gms. 
 
 Preparation for reduction 
 
 Temp, 
 of 
 reduc- 
 tion. 
 
 Nitros- 
 amine 
 gms. 
 
 Yield 
 
 Remarks 
 
 "5 
 
 Condensed over-night. Ppted. by 
 CO 2 ; dissolved in 40 ft H 2 SO 4 at 5. 
 
 in 
 ice 
 
 3-5 
 
 27 
 
 Precip- 
 itation 
 by CO, 
 
 10 
 
 Condensed 2 hrs. Pptd. by CO 2 ; 
 dissolved in 40 $ H 2 SO4 at i. 
 
 5-8 
 
 2.a 
 
 21 
 
 10 
 
 Pptd. by CO 2 ; diss. 4056 H 2 SO 4 at-2. 
 
 -2 to +8 
 
 2.2 
 
 21 
 
 12-5 
 
 Pptd. CH 3 COOH; diss. 50 H 2 SO 4 (ice) 
 
 in ice 
 
 2.9 
 
 22 
 
 Pptation. 
 CH 3 COOH 
 
 IO 
 
 Pptd. CH 3 COOH; diss. 40 H 2 SO 4 ,-2. 
 
 -2 to +8 
 
 2.1 
 
 20 
 
 20 
 
 Pptd. NaHCO 3 (large lump); diss. 
 in 40$ H 2 SO 4 at o. 
 
 c-6 
 
 4-0 
 
 19 
 
 NaHC0 3 
 
 10 
 
 Not isolated; sol. added to equal 
 vol. (190 cc.) 4o$H 3 SO 4 at 15. 
 
 J5- 
 33 
 
 2.2 
 
 21 
 
 Not 
 isolated; 
 not 
 cooled. 
 
 IO 
 
 Not isolated; sol. added to equal 
 vol. (130 cc.) 40 <jt, H 2 SO 4 at 17. 
 
 I7 o_ 
 37 
 
 2.7 
 
 26 
 
 The data in Table III indicate that 
 
 (a) The condensation-product may be precipitated equally 
 well by carbon dioxide or acetic acid, but less advantageously 
 by sodium bicarbonate. 
 
 (b) No advantage is gained by isolation of the condensation- 
 product. It is indicated also that low temperatures are not 
 essential (see Tables IV and V). 
 
 34 
 
METHYLATION OF PARA-AMINOPHENOL 
 TABLE IV. 
 
 Experiments to determine 
 
 (a) Effect of variation in concentration of acid. 
 
 (b) Effect of variation in volume in which reduction 
 occurs. 
 
 (c) Necessity for cooling before and during reduction. 
 
 P. A. P. 
 
 gms. 
 
 Preparation 
 for 
 Reduction 
 
 Temp. 
 of 
 Reduc- 
 tion 
 
 Nitros- 
 amine 
 gms. 
 
 * 
 
 Yield 
 
 Remarks 
 
 10 
 
 Pptd. by CH 3 COOH; dissolved in 
 25% H,S0 4 at 4 
 
 low 
 
 1.8 
 
 17 
 
 25 j H 2 S0 4 
 
 10 
 
 Pptd. by CH,COOH; dissolved in 
 40 # H 2 SO 4 at-2 
 
 -2 to 
 + 8 
 
 2.1 
 
 20 
 
 40* H 2 S0 4 
 
 10 
 
 Pptd. by CH 3 COOH; dissolved in 
 50* H 2 S0 4 at 4 
 
 low 
 
 i-9 
 
 18 
 
 50 + H 2 S0 4 
 
 10 
 
 Pptd. by CO*; dissolved in 190 cc. 
 40 * H 2 S0 4 at-5 
 
 2 
 
 1.6 
 
 15 
 
 
 IO 
 
 Pptd. by CH 3 COOH; dissolved in 
 50 cc. 40 < H 2 SO 4 at -5 
 
 -i 
 
 2.1 
 
 20 
 
 IO 
 
 Pptd. by CH 3 COOH; dissolved in 
 loo cc. 40 # H 2 SO 4 ,-8 to -2 
 
 -2 to 
 + 28 
 
 2.2 
 
 21 
 
 Effect 
 of 
 temp, 
 variations 
 
 IO 
 
 Pptd. by COo; dissolved in 40 # 
 H 2 SO 4 at 5 
 
 oto 
 + 5 
 
 2-5 
 
 24 
 
 10 
 
 Not isolated; equal volume (190 cc.) 
 40* H 2 SO 4 added, 15 
 
 '5- 
 33 
 
 2.2 
 
 21 
 
 IO 
 
 Not isolated; equal volume (130 cc. 'I 
 40 ^ H 2 SO 4 added, 17 
 
 I7- 
 32 
 
 2.7 
 
 26 
 
 The above experiments show that 
 
 (a) No decided effect is caused by variations in the initial 
 concentration of sulphuric acid. 
 
 (b) Somewhat better results are obtained when the volume 
 is restricted (see Table V). 
 
 (c) No advantage is gained by working at low tempera- 
 tures. 
 
 In subsequent experiments the condensation-product was not 
 isolated. The condensation liquid was transferred to a beaker, 
 provided with a mechanical stirrer, some zinc-dust was added, and 
 an excess of 40 per cent sulphuric acid was introduced. While 
 stirring actively, zinc-dust was added so as to maintain it in ex- 
 cess. In several experiments, the condensation liquid was added 
 
 35 
 
METHYLATION OF PARA-AMINOPHENOIv 
 
 slowly to an excess of acid and zinc-dust, 
 experiments are shown in Table V. 
 
 Results of further 
 
 which reduction 
 
 TABLE V. 
 Experiments to determine 
 
 (a) Effect of reduction at higher temperatures 
 
 (b) Effect of variations of volume in 
 occurs. 
 
 (c) Effect of gradual addition of condensation liquid to 
 sulphuric acid and zinc-dust. 
 
 (Reduction of methylene-p-aminophenol without isolation.) 
 
 P. A. P. 
 gms. 
 
 Preparation for reduction 
 
 Temp, 
 of 
 reduc- 
 tion. 
 
 Nitros- 
 amine 
 gms. 
 
 Yield 
 
 Remarks 
 
 10 
 
 Added equal volume (70 cc.) of 40 $ 
 H 2 S0 4 . 
 
 I5 -, 
 
 2.2 
 
 21 
 
 Average 
 temp. 5 
 
 10 
 
 Added 125 cc. 40$ H 2 SO 4 to solution 
 diluted to 400 cc. 
 
 * 5 V 
 
 3-3 
 
 31 
 
 35 
 
 10 
 
 Added equal volume (70 cc.) of 40$ 
 H 2 S0 4 . 
 
 50- 
 28 
 
 3-3 
 
 31 
 
 40 
 
 10 
 
 Added equal volume (120 cc.) of 40$ 
 H 2 SO 4 . 
 
 30- 
 86 
 
 3-6 
 
 34 
 
 " 60-80 
 
 10 
 
 Added equal volume (loocc.) of 40$ 
 H 2 SO 4 . 
 
 7 o- 
 90 
 
 3-3 
 
 31 
 
 90 
 
 10 
 
 Added equal volume (100 cc.) of 40$ 
 H 2 S0 4 . 
 
 65- 
 103 
 
 3-2 
 
 30.5 
 
 " 100 
 
 10 
 
 Added equal volume (65 cc.) of 40$ 
 H 2 S0 4 . 
 
 6o- 
 90 
 
 2-5 
 
 24 
 
 Reduction in 
 small vol. 
 
 10 
 
 Solution added dropwise to equal 
 volume (116 cc.) of 40$ H 2 SO 4 
 containing zinc-dust: 25 gms. 
 zinc in all. 
 
 20- 
 
 49 
 
 2-5 
 
 24 
 
 Condensa- 
 tion liquid 
 added to 
 zinc and 
 H 2 S0 4 
 
 10 
 
 Same as above; volume = 65 cc. 
 Added rapidly to zinc and H 2 SO 4 . 
 
 6o- 
 80 
 
 2.6 
 
 25 
 
 10 
 
 Same as above; volume = 100 cc. 
 Higher temperature. 
 
 8o- 
 90 
 
 3-0 
 
 29 
 
 The results in Table V justify the conclusions that 
 
 (a) The most favorable reduction temperature is rather 
 high, lying above 50, and probably at 70 to 80. 
 
 (b) Variations in the volume of the liquid in which re- 
 duction is effected do not have any definite effect 
 upon the results. Smaller volumes are preferable for 
 reasons of convenience. 
 
METHYLATION OF PARA-AMINOPHSNOI, 
 
 (c) No improvement is caused by gradual addition of the 
 condensation liquid to sulphuric acid in which zinc- 
 dust is kept in excess, to avoid prolonged contact of 
 acid and condensation-product before the latter can 
 be reduced. 
 
 Miscellaneous Experiments 
 Reduction of Dried Condensation-product 
 Eighteen grams of dried methylene-p-aminophenol were dis- 
 solved in 150 cc. of 40 per cent sulphuric acid, and reduced with 
 15 grams of zinc-dust at o to 5. There was obtained 2.2 grams 
 of nitrosamine, corresponding to n.6 per cent reduction. 
 
 In another experiment, methylene-p-aminophenol which had 
 become resinous on drying was similarly treated. In contact 
 with acid, the dark red powder coagulated into a single glue-like 
 mass, which remained unattacked upon addition of zinc-dust. 
 
 These experiments demonstrate the increased difficulty in re- 
 duction which is consequent upon drying the condensation-pro- 
 duct, presumably as a result of polymerization. 
 
 Effect of Presence of Excess Formaldehyde added to Conden- 
 sation-liquid previous to Acidification and Reduction 
 For experimental conditions, see last experiment in Table III. 
 After condensation, 10 grams of 38 per cent formaldehyde were 
 added, and then one volume of 40 per cent sulphuric acid. Re- 
 duction was carried out as usual. Addition of sodium nitrite 
 caused brisk effervescence, but no nitrosamine was formed. 
 
 The prevention of hydrolysis of methylene-p-aminophenol was 
 therefore not achieved, while normal reduction was in some way 
 prevented, by presence of excess formaldehyde in the acid solu- 
 tion. 
 
 From the preliminary experiments, the results of which are re- 
 corded above, was developed the procedure used in succeeding 
 experiments, in which the course of the reaction was examined 
 somewhat more closely. 
 
 The extent to which p-aminophenol escapes condensation with 
 formaldehyde is shown in Table I (page 24). The p-aminophenol 
 
 37 
 
METHYIvATlON OF PARA-AMINOPHENOI, 
 
 present after reduction includes this, in addition to any formed 
 by acid hydrolysis of the methylene-p-aminophenol. 
 
 Recovery of unchanged p-aminophenol from the solution after 
 reduction is readily effected by condensation with benzaldehyde. 88 
 For this purpose, the solution is nearly neutralized (left slightly 
 acid), sodium acetate is added, and the liquid is shaken with a 
 slight excess of benzaldehyde. The benzylidine p-aminophenol 
 separates as light-colored flocks or clumps, which adhere to the 
 vessel if too large an excess of benzaldehyde is present. The 
 precipitate, when completely formed, is filtered off, and washed 
 with water. It may be dried and weighed, i.o gram correspond- 
 ing to 0.73 gram of p-aminophenol hydrochloride. Benzylidine- 
 p-aminophenol is readily crystallized from dilute alcohol as small 
 pale yellow needles which melt at 185. It is well adapted to the 
 identification of p-aminophenol. 
 
 To recover p-aminophenol and benzaldehyde from benzylidine- 
 p-umino phenol, advantage was taken of the ready hydrolysis of 
 the last-named by strong acids. The product was transferred to 
 a distillation-flask, water added to make a paste, about an equal 
 weight of strong hydrochloric acid added, and the mixture dis- 
 tilled with steam. The benzylidine-p-aminophenol was thus de- 
 composed, and the benzaldehyde formed passed into the distillate. 
 It was extracted therefrom by ether, and recovered by distilla- 
 tion. The acid liquid from the decomposition was treated so as 
 to obtain the p-aminophenol hydrochloride ( see page 23 ) . Work- 
 ing in this way, there was obtained, from 37 grams of benzylidine- 
 p-aminophenol, 
 
 17.8 grams of benzaldehyde ( i78-i85) 90 per cent. 
 
 23.2 grams of p-aminophenol hydrochloride 85.6 per cent. 
 Preparation of N -Methyl- p-aminophenol from its Nitrosamine 
 
 Among the methods suggested for replacement of the nitroso- 
 group by hydrogen may be mentioned 
 88 D. R. P. 208434. 
 
 38 
 
METHYIvATlON OF PARA-AMINOPHENOI, 
 
 (a) Reduction by tin, zinc, or iron, and acid. 89 It will be 
 recalled that by milder reduction, hydrazine deriva- 
 tives are formed. 90 
 
 (b) Action of strong hydrochloric acid, or gaseous HC1. 91 
 
 (c) Heating with aniline. 92 
 
 Several attempts to convert p-oxy-phenylmethylnitrosamine to 
 the secondary base, by action of hydrochloric or sulphuric acid, 
 resulted unsuccessfully. Decomposition occurred readily, with 
 evolution of nitrogen oxides, but the decomposition was accom- 
 panied by considerable tar- formation, so that only small amounts 
 of crystalline product could be isolated from the black and vis- 
 cous liquid. 
 
 Reduction of the nitrosamine with zinc and hydrochloric acid 
 was more successful, and was conducted thus: 10 grams of 
 nitrosamine was suspended in water with 20 grams of zinc-dust. 
 While stirring (mechanically), 75 cc. of strong hydrochloric acid 
 was added from a separatory funnel, at such a rate that the tem- 
 perature did not exceed 50. When action was at an end, the 
 liquid was treated with ammonium chloride, made alkaline with 
 ammonia (using enough to hold the zinc in solution), and ex- 
 tracted with ether. The residue from the evaporation of the 
 ether was taken up in a little dilute sulphuric acid, the liquid 
 digested with animal charcoal, and crystallized. There were ob- 
 tained 4.2 grams of the sulphate, corresponding to 37 per cent. 
 As several trials resulted no better than this, it was decided to 
 isolate the methylated base as such, without intermediate for- 
 mation of the nitrosamine. 
 
 Procedure for Methylation of p-Amino phenol, with Final Ex- 
 perimental Results 
 
 Condensation This operation was conducted as described on 
 page 25, paragraph (a). 
 
 Reduction Transfer the solution to a beaker, into which is 
 89 Noelting and Boasson, Ber., 10, 795 (1877); Weyl, "Methoden", I, 
 219 (1911). 
 
 90 Weyl, /. c.\ Backer, Rev. trav. chim., 32, 39. 
 
 91 Geuther, AnnaL, 128, 151 (1863); Stoermer, Ber., 31. 2523 (1898). 
 91 Henriques, Ber. y 17, 2671 (1884). 
 
 39 
 
METHYIvATlON OF PARA-AMINOPHENOI, 
 
 suspended a mechanically operated stirrer, and a thermometer; 
 the beaker is supported on a plate above a bunsen burner. Weigh 
 out i to 1.5 times as much zinc-dust as was taken of p-amino- 
 phenol, and introduce a portion of it into the beaker. Warm to 
 about 50 a volume of 40-50 per cent sulphuric acid equal to 
 that of the condensation liquid, and add it all at one time. While 
 keeping the stirrer in rapid motion, add the zinc steadily and in 
 small portions with sufficient rapidity that the solution is con- 
 tinually filled with gas-bubbles. Raise the temperature as quickly 
 as possible to 7O-8o ; this is much assisted by adding the zinc 
 in larger portions at first. Keep the temperature near 80 by 
 application of heat, until all the zinc has been added, and has 
 dissolved. The liquid will be entirely clear and colorless, except 
 for a small amount of insoluble matter from the zinc. 
 
 Removal of Unaltered p-Aminophenol 
 
 Almost neutralize the liquid with sodium hydroxide, add 
 sodium acetate, transfer to a capacious Erlenmeyer flask, and 
 cool. Add a slight excess of benzaldehyde (3 or 4 grams for 
 each 10 grams of p-aminophenol hydrochloride taken initially 
 should be ample), and shake the stoppered flask. After the 
 benzylidine-p-aminophenol has separated, filter it off, and wash 
 with water. It may be treated as outlined on page 38 for recovery 
 of benzaldehyde and p-aminophenol hydrochloride. 
 
 Isolation of N-Methyl-p-ammophenol as Sulphate 
 Transfer the filtrate to a distillation-flask, and distil in steam 
 until all excess of benzaldehyde is removed. Concentrate the 
 liquid nearly to separation of salts, cool, add ammonium chloride, 
 and then strong ammonia until the precipitated zinc redissolves. 
 Extract the alkaline liquid four or five times with ether, which is 
 then distilled off. Take up the residue in enough 40 per cent 
 sulphuric acid to establish distinct acidity, and cool the liquid 
 strongly. It should set to a stiff magma containing crystals of 
 the sulphate. Filter, and wash the crystals with alcohol. Con- 
 centrate the filtrate to obtain a further crop of the sulphate. 
 Digestion with good animal charcoal will assist the crystallization 
 by elimination of tarry material. These crystallizations may 
 
 40 
 
METHYIvATlON OF PARA-AMINOPHENOI, 
 
 cause some trouble, due to the rather viscous nature of the liquid, 
 and to the presence of impurities which appear to retard crystal- 
 formation. 
 
 Additional solid material may be obtained from the final 
 mother-liquor by evaporation to pastiness, and extraction with 
 alcohol. A light gray powder is thus obtained (as a residue in- 
 soluble in alcohol), which contains some methyl-p-aminophenol 
 sulphate, but is evidently composed largely of some other sub- 
 stance, which is very soluble in water. This material has usually 
 given the nitrosamine reaction, and with mercuric acetate de- 
 veloped a strong blue color (see page 28). It cannot easily 
 be crystallized, because of its high solubility. Benzoylation of 
 some of this substance yielded a product which melted at 132- 
 134. Recrystallization of the main product affords a separation 
 of the methyl-p-aminophenol sulphate from the more soluble 
 compound. The mother liquors, however, always contain very 
 appreciable quantities of the former, as may be demonstrated by 
 precipitation as nitrosamine. 
 
 The ether extraction was a rather troublesome operation. The 
 quantity of ammonia required to hold the zinc in solution ren- 
 ders the liquid somewhat bulky for hand-extraction ; a mechanical 
 shaker, or the continuous extraction device of Schwarz 93 would 
 be of great assistance. During the extractions, there was a 
 continual separation of a black foam-like material, which ap- 
 peared to fill the ether layer completely ; this was filtered off from 
 time to time. The ether extracts were bright red in color. The 
 complete removal of the coloring-matter requires many extrac- 
 tions, and is thought to be unnecessary, as methyl-p-aminophenol 
 is very soluble in ether. 
 
 In the experiments tabulated below, aliquot portions were in 
 most cases examined for uncondensed p-aminophenol after the 
 condensation, and again after reduction; the extent of the re- 
 duction was determined by nitrosamine precipitation in another 
 aliquot portion. The indicated yields are calculated on the basis 
 of the weight of p-aminophenol hydrochloride actually subjected 
 
 n Ber., 17, Ref. 402 (1884); Weyl, "Methoden", General Part, p. 131 
 (1909). p. 515 (1921). 
 
 41 
 
METHYLATION OF PARA-AMINOPHENOL 
 
 to methylation, and not recoverable (compare Tables III, IV, V). 
 The main portion of each experiment was treated for separation 
 of the methylated base in the form of its sulphate. Freed from 
 detailed data, and expressed only in nearest percentages, the re- 
 sults of the final experiments are as shown in Table VI. 
 
 TABLE VI. 
 
 Yield of 
 cond. 
 prod. 
 
 recovered 
 after 
 cond. 
 
 recovered 
 after 
 reduction 
 
 produced 
 by by- . 
 drolysis 
 
 Yield 
 based on 
 nitros- 
 amine 
 
 Yield 
 based on 
 sulphate 
 
 P. A. P. 
 acctd. for 
 
 % 
 P. A. P. 
 not 
 acctd. for 
 
 
 
 - 
 
 26 
 
 - 
 
 36 
 
 - 
 
 - 
 
 - 
 
 
 
 - 
 
 35 
 
 - 
 
 47 
 
 23 
 
 66 
 
 34 
 
 6? 
 
 29 
 
 40 
 
 11 
 
 47 
 
 37 
 
 68 
 
 32 
 
 77 
 
 21 
 
 32 
 
 11 
 
 39 
 
 28 
 
 59 
 
 41 
 
 77 
 
 21 
 
 , 25 
 
 4 
 
 30 
 
 31 
 
 48 
 
 52 
 
 - 
 
 - 
 
 33 
 
 - ' 
 
 - 
 
 28 
 
 52 
 
 48 
 
 From these results it may be concluded that 
 
 (a) About one- fourth of the p-aminophenol taken escapes 
 condensation with formaldehyde. 
 
 (b) Hydrolysis of the condensation-product during reduc- 
 tion removes from the reaction an additional 10 per cent of 
 p-aminophenol. 
 
 (c) The process is effective in methylating about 40 per cent 
 of the p-aminophenol brought into reaction, as determined by 
 precipitation of the secondary base as nitrosamine. 
 
 (d) The yield of the process, in terms of the secondary base 
 itself, isolated as its sulphate, and referred to the amount of 
 p-aminophenol actually subjected to methylation, is about 30 per 
 cent. The method of isolation is insufficiently perfected. 
 
 (e) Of the total p-aminophenol initially taken, about 60 per 
 cent can be accounted for, either as methylated base, or as un- 
 changed p-aminophenol, which can be recovered without trouble. 
 
 (f) Approximately 40 per cent of the p-aminophenol initially 
 taken enters into some side-reaction, and has not been accounted 
 for. 
 
 42 
 
t * o 
 
 ""* ' * fc * 
 
 METHYIvATlON OF PARA-AMINOPHENOI, 
 
 Identification of N-M 'ethyl- p-amino phenol, produced from 
 p-Aminophenol by the Method described above 
 
 (1) Nitrosamine melted at 133 (corr.). 
 
 (2) Dibenzoyl-derivative melted at 174 (corr.). 
 
 (3) Sulphate (Metol) charred at 242, and melted at 257. 
 
 (4) Nitrogen Determination (Kjeldahl) : 
 
 Found: 8.01 
 
 7.84 Average=7.9% 
 
 7-85 
 
 Calculated for 
 
 (HO.C 6 H 4 .NH.CH 3 ). 2 H,SO 4 : 
 
 8.14% 
 
 (5) Sulphate responded strongly to mercuric acetate test. 
 
 (6) A photographic film was developed by a solution con- 
 taining a little of the sulphate, sodium sulphite, and 
 sodium carbonate. 
 
 IV. Summary 
 
 (1) The available methods for conversion of the condensa- 
 tion-products of p-aminophenol and formaldehyde into N-methyl- 
 p-aminophenol have been reviewed, and applied experimentally. 
 
 (2) The reduction of N-methylene-p-aminophenol (produced 
 by condensation of p-aminophenol with formaldehyde in alkaline 
 solution) by zinc-dust and sulphuric acid has in particular been 
 subjected to investigation, and the course of the reaction has 
 been studied. 
 
 (3) It has been found that the condensation of formaldehyde 
 and p-aminophenol in alkaline solution is from 70 to 85 per cent 
 complete; that during reduction by zinc and acid a further 10 
 per cent of the initial p-aminophenol is freed by hydrolysis of 
 the condensation-product ; that about 40 per cent of the p-amino- 
 phenol which actually enters the reaction as methylene-p-amino- 
 phenol, and is subjected to reduction, is methylated. The un- 
 changed p-aminophenol may be recovered after removal from 
 the solution as benzylidine-p-aminophenol after the reduction. 
 
 43 
 
THIS BOOK IS DUE ON THE LAST DATE 
 STAMPED BELOW 
 
 AN INITIAL FINE OF 25 CENTS 
 
 WILL BE ASSESSED FOR FAILURE TO RETURN 
 THIS BOOK ON THE DATE DUE. THE PENALTY 
 WILL INCREASE TO SO CENTS ON THE FOURTH 
 DAY AND TO $1.OO ON THE SEVENTH DAY 
 
 JUL 12 1933 
 
 MAY 13 1938 
 
 APR 2 7 1966 5 9 
 
 LD 
 
 LD 21-50m-l,'3! 
 
488068 
 
 j 
 
 UNIVERSITY OF CALIFORNIA LIBRARY