L. CHAS. RAIFORD “TO
L. C. R. HONORED TEACHER WELL-LOVED FRIEND”
Such was the dedicatory statement in J. C. Colbert’s “Laboratory Technique of Organic Chemistry.”l The death of Professor L. Chas. Raiford on January 8, 1944, at the age of seventy-one, removed from our midst a chemist for whom the above dedication stands as a splendid epitome of the place he had won for himself among American organic chemists. Lemuel Charles Raiford was born August 2, 1872 in Southampton County, Virginia. In 1895 he received the Ph.G. degree from the Maryland College of Pharmacy; in 1900 and 1904, respectively, he was awarded the Ph.B. and A.M. degrees by Brown University. He took his Ph.D. degree in 1909 at the University of Chicago with Professor J. Stieglitz, and the influence of Stieglitz was apparent throughout Raiford’s subsequent professional career. The marriage of Lemuel Charles Raiford to Sara Alice Broomhead of Seekonk, Massachusetts on December 26, 1901, led to a pleasant home which they enjoyed for over thirty-seven years until the death of Mrs. Raiford in 1939. There waa but one child, the daughter, Alice Mary (Mrs. Mark Hagerman). She and her father were great companions, and it was with her and her family (Dr. Mark Hagerman and Mark, Jr.) that Professor Raiford spent his short vacations each summer for the last several years of his life. In a letter some weeks after his death, Mrs. Hagerman wrote: “He hoped he would go with his boots on and he did. To me his life was just like a beautiful book with a perfect ending. But we shall never forget Lem and the things he stood for. I feel that he made an everlasting impression on my fifteen year old son who worshiped Lem and with whom Lem spent some very happy hours. . . . Those days are precious memories now.”
Early in his career, Raiford held a number of positions, of several types and in several locations. Following his undergraduate work at Brown University, he remained at that institution as Instructor in Chemistry for the year 19001901, and he held a like position at Clemmn College in 1901-1902. Between 1902 and 1907 he was Associate Professor of Textile Chemistry and Dyeing at the Mississippi Agricultural and Mechanical College. For the next two years he was an Associate in the Chemistry Department at Chicago while working with Stieglitz. From Chicago he traveled to the University of Wyoming where from 1909 to 1911 he worked as a research chemist in the experiment station. In 1911 he returned to Chicago as Instructor in Chemistry and remained there until 1915 1
I). Appleton-Century Co., Inc., New York, N. Y., 1933. 87
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when he was appointed Professor of Chemistry at the Oklahoma Agricultural College. In 1918 he was called to the State University of Iowa as Associate Professor and Head of the Division of Organic Chemistry; advancement to Professor followed in 1927. This post he held until his seventieth birthday in 1942; subsequently he continued his research activities and part-time teaching duties until but a few days before his death. During the summer of 1930 he had been Visiting Professor of Chemistry at Western Reserve University, and he had served at the University of Nebraska in a similar capacity during the summer of 1932. Professor Raiford was active in a number of scientific and professional organizations and societies. Among these were: the American Chemical Society, the American Association for the Advancement of Science, the American Institute of Chemists, Sigma Xi, Phi Beta Kappa, the Iowa Academy of Science, the Oklahoma Academy of Science, the New York Academy of Science, Alpha Chi Sigma, Phi Lambda Upsilon, Phi Delta Chi, the American Association of University Professors, and the Research and Triangle Clubs of the State University of Iowa. He was ever willing to be of service, regardless of the work involved, in those organizations of which he was a member. In 1916 he was Vice-Prksident and in 1917 President of the Oklahoma Academy of Science, and in the Iowa Academy of Science he had served as Chairman of the OrganicBiochemistry Section. That he was, for several years, a member of the Executive Committee of the Division of Organic Chemistry of the American Chemical Society and Chairman of the Division in 1937, that he was nine times Councilor from the Iowa Section of the American Chemical Society, and that he was a member of the Board of Editors of the Journal of Organic Chemistry from the date of publication of the first number (1936) to the time of his death are proof of the high regard he enjoyed among his fellow chemists in this country. In addition to his teaching and research activities, some of his greatest service to the State University of Iowa was his constant interest in and endeavors on behalf of the chemistry library. Raiford served as departmental representative on the University library board for many years, and he was in no small way responsible for the present excellence of the chemistry library. At the dedication of the new chemical laboratory at the University of Oklahoma (1917), L. Chas. Raiford delivered the principal address. On this occasion, rather early in his productive professional life, he enunciated certain principles which were to guide his subsequent endeavors. Raiford adopted for his own, what he cited as the conclusions of ex-President Eliot of Harvard University concerning the educational desires of his generation: “The first is a desire for a sound knowledge of the facts, and the second is an intense desire to be of service t o mankind.” Raiford held that: “First, there must be adequate training in the fundamentals of chemistry, and second, there must be opportunity for chemical research.” To those who clamored for applied science and more of it, his reply was: li. . . there can be no applied science until there is science to apply.” Reports published while he was at the University of Wyoming demonstrate that Raiford could produce results on problems of immediate practical importance,
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but he chose to devote most of his time and effort to pure science and fundamental investigations. He firmly believed that “Some one must patiently and laboriously determine the facts and formulate the principles before there can be any commercial application of them; and, whether we recognize it or not, the world is maiting on the research worker.” Professor Raiford attained distinction in two respects-as a teacher and as a research worker. Of Raiford the teacher, Professor George H. Coleman, his colleague of over twenty years, stated: “Professor Raiford was a n exceptionally able teacher. In his quarter century of service at the University, innumerable students have had the benefit of his unusually clear lectures in organic chemistry and have enjoyed his dry humor. His colleagues will remember him for his good fellowship and absolute integrity.”
The following, an excerpt from one of Raiford’s publications, illustrates something of his thoroughness, his understanding, and his method in the class room. “In presenting a new term t o a class i n chemistry, the teacher should keep i n mind the possibility that the students may memorize the definition recorded in the book, or that given by the lecturer, without recognizing any connection between the term and the chemical behavior to which i t relates. I n some cases a lecture experiment may help to make the connection clear. “In order that such a demonstration may be successful and carry the correct idea to the student, i t must meet certain requirements. It goes without saying that the experiment must work. T o insure this, every part of the apparatus should be carefully examined beforehand by the lecturer or the experiment run through before the class comes in. The apparatus should be simple, the reaction should be direct and rapid. Some definite relationship should be illustrated by the experiment, and special pains should be taken to explain this relationship in terms with which the students are already familiar, including the necessary equations, when possible. .”
..
The influence of his master, Stieglitz, was conspicuous in his teaching-in courses offered, in subject matter included, in method of presentation. Almost periodic references t o Stieglitz by name apprised the student of Raiford’s tremendous regard for his mentor and his high standards. Without doubt, students of Raiford now in academic positions recognize, likewise, the influence of their master on them, and this consciousness serves as an incentive t o spur them on to better performance of their duties. System and completeness, clarity and finish, pertinent quotations and cogent demonstrations-these characterized his lectures. His small stature and quiet personal manner were presently forgotten by inembers of a new class, for because of his enthusiasm for and complete absorption in his subject and his forceful expositions and presentations of topics he all but became a part of his subject; he was not just the lecturer. Too, he was thorough; and it was expected that students likewise would be thorough. Probably none of his students fails to recall what so frequently appeared a t the end of an examination question: . . and leave no point in doubt.” At the time of his retirement as Head of the Division of Organic Chemistry in 1942, a dinner was held in his honor, and a gift was presented to him by former students ((.
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as a slight token of their esteem. The news letter of the Iowa Chapter of Alpha Chi Sigma, in the next issue thereafter, carried the very apt comment: “As most of you no doubt know, Dr. L. C. (Uncle Charley) Raiford has retired from full time service to the department. Those of us who know Dr. Raiford, however, realize that this is retirement in name only. Uncle Charley can’t be retired from his work no matter what the University regulations say. He is still the hardest, most sincere worker that we have seen in many a blue moon.”
Such was characteristic of the impressions which he left on his students. Raiford’s first real introduction into research was with Professor Stieglitz. He was one of the group of Earle, Hale, Eckstein, Hilpert, Peterson, and others mho investigated problems of the stereoisomerism of nitrogen compounds. Here again the directw wielded tremendous influence on the student. Introductions were made to types of interesting compounds and phenomena, fields of work and methods of investigation, respect for the masters of the science-their works and points of view, and recognition of the possible limitations of one’s own observations and conclusions. Just following Professor Raiford’s death, Professor H . A. Mattill wrote of him and his work: “Professor Raiford enjoyed the rigor of the game and his students learned how t o play it. No mushy generalities were permitted; clean-cut ideas and their accurate expression were the rule. By his simple insistence on rigid thinking, workmanlike performance, and accurate observations, he helped t o cultivate, in associates and students alike, an appreciation of the exacting requirements of true research. The fidelity with which he himself lived up to these ideals without ostentation is a quality worthy of emulation and an enduring legacy.”
To attempt to review completely the research works of Professor Raiford would exceed the intent of this report and would require more than the available space. However, in order to present something of his approach to a problem and method of inquiry into it, an outline of two or three of his researches can be given. “It has long been known that. . . .” “The ease with which this reaction took place, and the excellent yields . . .” suggested further general study. These introductory statements in the first of Raiford’s papers on the Zincke method of nitration are particularly characteristic. Repetitions of Zincke’s work on the nitration of tribromo-m-cresol had yielded isomers where Zincke had reported only one product. A systematic investigation of the reaction was undertaken, and interesting results were obtained. It was shown that when 2 ,4,6-trichloro-, -tribromo-, and -triiodophenol were treated with sodium nitrite in the presence of acetic acid, chlorine n-as not replaced by the nitro group, that a bromine or an iodine atom could be replaced under these conditions, and that the iodine was more easily replaced than the bromine. Further, although only one nitro product had been isolated previously from the bromo compound, it mas shown that both 4,6dibromo-2-nitrophenol and 2 6-dibromo-4-nitrophenol were formed ; analogous results were obtained with the iodo compound and other related halogenated phenols. When 4-bromo-2-chlorophenol was used as starting material, the and 2-chloro-4-nitrousual treatment yielded 4-bromo-2-chloro-6-nitrophenol phenol. These results, for the first time, showed the introduction of the nitro
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group in place of a hydrogen atom by the Zincke method, and further demonstrated the greater ease of replacement of bromine than chlorine by the nitro group. Such observations were substantiated by a study of 2-bromo-4-chloro-5methylphenol. When the tribromodimethylphenols were subjected to the conditions of the Zinclie reaction, a new observation was made. In addition to some replacement of bromine by the nitro group, quinone formation mas found to be characteristic of certain of these compounds. For example, 2 ,4,6-tribromo-3,5-dimethylphmol yielded 2 ,6-dibromo-3 ,5-dimethyl-4-nitrophenoland 2 ,6-dibromo-3,5diniethylbenzoquinone. (4,6-Dibromo-3 ,5-dimethyl-2-nitrophenol was prepared, but this was accomplished by other means than the Zincke method.) Isomeric and related compounds behaved similarly. In one of the early studies, 2,4,6-tribromoresorcinol had been investigated, and what was believed to be 2,6-dibromo-4-nitroresorcinol had been obtained. Later the monomethyl ether of resorcinol vias treated in the usual manner, and the product was shown to be 2,4-dibromo-3-methoxy-6-nitrophenol. From 4 ,5,6-tribromo-2-methoxyphenolno reaction product resulted by the Zincke method, and the action of nitric acid gave only a trace of nitro compound. However, the acetate and the benzoate were treated with fuming nitric acid and acetate and the corresponding yielded 4 ,5 ,6-tribromo-2-methoxy-3-nitrophenyl m-riitrobenzoate. The acetate and the benzoate of 4,5-dibromo-2-methoxyphenol were acted upon by sodium nitrite-acetic acid mixtures, and in one case bromine was replaced by the nitro group and the product was 4-bromo-2-methoxy-5-nitrophenyl acetate; other products were 4 ,5-dibromo-2-methoxy-3nitrophenyl acetate and the corresponding benzoate. It was argued that, in these changes, acylation of the phenolic hydroxyl groups suppressed their directive influences. Finally, in one of the last papers of the series, it was demonstrated that in bromofluorophenols, fluorine is not replaced by the nitro group by the Zincke method, even though fluorine is in a favored position; the behaviors of bromofluorophenols are analogous, then, to those of bromochlorophenols under similar conditions. In the work with compounds of the type mentioned above, a number of very instructive and quite rigorous proofs of structures were involved. The use of a series of closely related compounds and thorough study of their behaviors, as reported in this group of papers, is illustrative of Raiford’s approach and method. An even more complete example illustrative of his thoroughness in investigations is the series of researches on the o-aminophenol problem summarized below. I n an investigation involving various factors governing acylations of aminophenols, it was found that only one mixed acetyl benzoyl derivative of o-aminophenol could be obtained, regardless of the order of introduction of the acyl groups, and that the product was the N-benzoyl compound. I n the original paper of this series, Raiford, in what was for him a typical statement, pointed out, that “this made it a matter of much interest t o determine whether the . . . . observation represented merely an isolated case or was an example of a more general reaction.” The introductory report included results with acetyl and and benzoyl derivatives of o-aminophenol, 2-amino-6-brom0-4-methylpheno1,
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2-amino-4,6-dibromophenol,and it was observed that the presence of “acid forming substituents” was not responsible for the rearrangement which must have occurred. It was recognized that factors other than weight of acyl alone might be involved, and further work was outlined to test the influences of the positions occupied by the functional groups (OH and NH2) and differences in chemical characteristics (especially relative acidities) of acyls. Further work included the use of the acetyl and benzoyl derivatives of related o-aminophenols such as : 6-chloro-4-methyl-, 4-bromo-6-methyl-, 4-bromo-5methyl-, 4,6-dibromo-5-methyl-, 3,6-dibromo-4-methyl-, 3,4,5-tribromo-Gand 4-phenyl- derivatives of 2-aminophenol. methyl-, 3,5,6-tribromo-4-methyl-, Migrations mere observed, likewise, in these instances. On the other hand, no rearrangements were encountered with mixed diacyl derivatives of: p-aminophenol, the 2,6-dibromo-, 6-bromo-2-methyl-, and 2 , G-dibromo-3-methylderivatives of 4-aminophenol, 4-(4-aminophenyl)phenol, 7-amino-2-naphtho1, 2-amino-l-cyclohexanol, o-hydroxybenzylamine, o-aminobenzyl alcohol, and alpha-aminobenzyl-2-naphthol.It was concluded that the locations of oxygen and nitrogen on adjacent carbons of aromatic nuclei were rather essential and that the changes involved were reasonably specific for o-aminophenols. In a number of investigations, structural proofs were based, in part, upon this generalization. Again, this use of a large number of isomeric or closely related compounds was characteristic of much of Raiford’s work. From 8-amino-l-naphthol only one mixed diacyl derivative was obtained; a migration must have occurred. This suggested that the functional groups were in approximately the same proximity as in o-aminophenol. The isolation of isomeric mixed diacyl derivatives of 7-amino-2-naphthol1 on the other hand, was evidence, it was argued, of greater distance between the hydroxyl and amino groups than would be expected in terms of the folded formula which had been proposed at one time for the naphthalene nucleus. Arguments against the Kauffler formula for biphenyl were raised because mixed diacyl derivatives of 4-(4aminopheny1)phenol failed to behave as those of an o-aminophenol. To determine the influences of relative weights and chemical characteristics of acyl groups, a large number were employed-and in various combinations: acetyl and various other fatty acyls, phenylacetyl, o-chlorophenoxyacetyl, benzoyl, nitro and halogen substituted benzoyls, p-toluyl, naphthoyls, carboaryloxyl, methylphenylcarbamyl, diphenylcarbamyl, furoyl, and benzene- and p-toluenesulfonyl. I n summary, it may be stated that when combinations of acyls of the types RCO- and ArCO- were used, the heavier and more acidic group finally was found attached to nitrogen, and when ROCO- was one acyl of a pair with RCO- or ArCO-, usually the former was located on nitrogen, regardless of the order of introduction. (Some irregularities were noted. For example, when acetyl and o-chlorophenoxyacetyl were the two acyls used, o-chlorophenoxyacetylation of 2-acetylamino-G-bromo-4-methylphenol gave a product which upon partial hydrolysis yielded the N-o-chlorophenoxyacetyl derivative, but when benzoyl was used in place of acetyl, the isomeric mixed diacyl derivatives were stable and rearrangement did not occur during either acylation or hydrolysis.) From the studies it was clear that some migrations occurred during
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acylation and others during partial hydrolysis. I n the latter cases, N-acyl-oaminophenols mere obtained. With certain other types of acyl groups, somewhat different results were found, and the problem was expanded to several related types of investigations. When one of the acyls was that from a sulfonic acid and the other RCO- or ROCO-, no rearrangements were noted. This, it was argued, represented an exception t o Latimer’s theory of relative stabilities of isomers based on energies of repulsion between atomic kernels. Benzoxazolone formation was shown to be characteristic of such compounds as N-arylsulfonyl substituted o-aminophenols when they were treated with alkali. Usually, the benzoxazolone was formed, also, when a N-tosyl-o-aminophenol was treated with phenyl chlorocarbonate? however, a small amount of mixed diacyl derivative could be isolated in some cases (but tosyl always remained on nitrogen). On the other hand, when an 0-tosyl-o-aminophenol was treated with phenyl chlorocarbonate, a mixed diacyl derivative was obtained (without rearrangement), and when the product was dissolved in pyridine, heated, and allowed t o stand, a uretedione was produced. Some migrations with carbamyl substituted derivatives of o-aminophenols were reported, e.g., partial hydrolysis of O-diphenylcarbamyl-N-acetyl- or benzoyl-o-aminophenol gave N-diphenylcarbamyl-oaminophenol; the action of alkali on the latter yielded a benzoxazolone. However, with diphenylcarbamyl on oxygen and an arylsulfonyl group on nitrogen, partial hydrolysis did not effect rearrangement. Another example of benzoxazolone formation was encountered with the hydroxyphenylurethans obtained by the reduction of o-nitrophenylalkyl carbonates and subsequent migration of ROCO- from oxygen t o nitrogen. Further, benzoxazolone formation from an isocyanate by the action of thionyl chloride was shown t o be specific for phenyl isocyanate and not characteristic of a negatively substituted phenyl or an alkyl isocyanate. Reduction of o-nitrophenyl furoate was shown to result in migration of the acyl from oxygen to nitrogen under some conditions and t o result in benzoxazole formation under slightly different conditions. The following mas proposed as the mechanism for the change:
NO2
0
OH
0
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L. CH.46. RAIFORD
A uretedione was produced by the action of phosgene on 2-amino-6-bromo-4phenyl p-toluenesulfonate. An interesting behavior was noted when a uretedione was treated with methylamine; thus, H
Ar--“C=O
I 1
yielded a substituted biuret,
O=C-N-Ar
0
Ar 0
\ II I II N-C-X-C-X /
Ar
H
/ \
CHs
An outgrowth of the studies on acyl derivatives of o-aminophenols was the introductory work on derivatives of the phenylenediamines. Aminoamides,
e4.7
v\N-C-0-Ar I
, were
prepared by reduction of the corresponding
II
H O nitro amides. Heat converted the product to a cyclic urea or benzimidazolon with the elimination of phenol. When chlorine, for example, was a substituent in the aryl group, the amino amide was less stable and, on reduction, the benzimidazolon was produced immediately. The isomeric derivatives of the mand p-phenylenediamines were more stable, as was expected, and cyclic ureas were not produced. Another series of studies may be grouped together and referred to as the vanillin problem. The vanillin molecule with its multiple functions-aldehyde, phenol, ether-offered almost unlimited opportunities to the organic chemist, and it and related compounds intrigued Raiford. Undertaken in connection with the vanillin problem were proofs of structures, completions of series, several types of condensations, and theoretical problems of orientation, steric hindrance, and stereoisomerism. The possible chlorine, bromine, and iodine substitution products of vanillin were prepared, and their structures were proved conclusively. I n several instances, this involved corrections of structures which had been assigned by previous investigators. Some similar nitrovanillins were studied also. Observed in these investigations were modifications of directive influences of substituent groups. A case in point is the suppression of the influence of a hydroxyl group when it was acylated. It was shown that in benzoyl vanillin, for example, the methoxyl group is more effective in determining the position to be taken by an entering substituent than the acyloxyl group, and in one report it was shown, further, that the para directing effect of methoxyl is greater than its ortho orienting influence. Some reactions were encountered in which chlorine did not enter a molecule in the same position as that taken by bromine under similar conditions; this “shows that the position taken is, in part, dependent on the character of the entering substituent.’’ Steric hindrance in substituted vanillins was studied in reactions with compounds containing amino groups. Such changes as the Perkin reaction, Claisen’s reaction, and the benzoin condensation were investigated with respect to vanillin and substituted vanillins. The condensation of vanillin and a number of its substitution products with
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nitromethane to give the related P-nitrostyrenes was the subject of an interesting research. The formation of azlactones from vanillins and aceturic or hippuric acids was observed, and some of the products were studied. Possible stereoisomerism in the case of oximes was another aspect of the problem investigated. Related compounds were studied in analogous, if less complete researches. Obviously, isovanillin was included, especially in connection with orientation studies. The cinnamic acids obtained from vanillins were oxidized ; rather than the possible vanillic acids, the aldehydes mere recovered. The vanillic acids were prepared, however, from oximes by conversion to acetyloxynitriles and hydrolysis to acids. Later it was demonstrated that acyl derivatives of p hydroxycinnamic acid can be oxidized, under conditions which prevent hydrolysis, to the corresponding acyloxybenzoic acids. Some steric hindrance was noted in connection with hydrolyses of nitriles to related vanillic acids. Substituted veratraldehydes and veratric acids were investigated, and these researches included some excellent proofs of structures. Another series of papers included an extensive and exhaustive study of factors involved, especially the effects of substituents, in the rearrangements of hydrazones to pyrazolines. Limitations of the reactivities of carbonyl compounds occupied the attention of Professor Raiford and his students for a number of years. An interesting group of reports appeared on the preparation and decomposition of alkyl aryl and diary1 ethers. In addition t o these and the types of problems referred to above, a number of miscellaneous questions were studied and reports on them are to be found in the literature. Study of a group of papers from Raiford’s laboratory on one of the general topics is instructive to the reader because of the sound approaches, the keen observations, and the skillful handling of problems. The report based on his dissertation was an early indication of the indefatigable worker and capable, painstaking experimenter which he was. Investigations frequently involved standard reactions and simple apparatus, but soundness of work and rigid adherence to high standards mere never sacrificed. His was a remarkable ability to select a problem and set a student to a task of investigation which would lead to definite results. Earlier papers contained careful reviews of the literature and were highly documented; these are very instructive and reveal the great care with which a problem was considered before it was taken to the laboratory. More recently, necessary editorial policies detracted somewhat from this aspect of the reports. One will do well to attempt to emulate Raiford’s unselfish accomplishments for science and the good of mankind. His was great devotion to his work. His TVS unusual influence on students. His were sound contributions to organic chemistry. 30 more appropriate words can be written of L. Chas. Raiford than to repeat his own tribute to his great friend J. N. Pearce: “Few have served longer in a single academic post, and none more faithfully.”e STEWART E. HAZLET OF WASHINGTON STATECOLLEGE 2
Paper No. 82 i n list of publications.
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PUBLICATIONS OF L. CHAS RAIFORD 1. “The Replacement of Halogen by the Nitro Group,” Am. Chem. J . , 43, 393 (1910) (with Heyl). 2. “The Replacement of Halogen by the S i t r o Group,” Am. Chem. J . , 44, 209 (1910) (with Heyl). 3. “Analysis of Zygadenus intermedius,” J . Am. Chem. SOC.,33, 206 (1911) (with Heyl). 4. “Chemical Examination of Woody Aster,” J . Am. Chem. SOC.,33, 1185 (1911). 5. “Woody Aster,’’ U.of Wyom. Agr. Exp. Sta. Prelim. Bull. 88 (1911) (with Prien). 6. “On Chlorimidoquinones,” Am. Chem. J . , 46, 417 (1911). 7. “The Action of Halogen on 4-Sitro-m-cresol,” J . Am. Chem. SOC.,36,670 (1914). 8. ‘L4-Bromo-6-nitro-m-cresoland Some of Its Derivatives,” J . Am. Chem. SOC., 36, 1498 (1914) (with Leavcll). 9. “Relationships of Chemistry and Life,” Science, 46, 489 (1917). 10. “Molecular Rearrangement in the ilcylation of Certain Aminophenols,” J . Am. Chem. SOC.,41, 2068 (1919). 11. ‘
