\ ARTIFICIAL MUSKS: THE STABILITY OF THE ISOPROPYL GROUP IN CYMENEAND ITS DERIVATIVES I1Y MORIS HOWARD JOFFE THESIS FOR THE DEGREE OF BACHELOR OF SCIENCE CHEMICAL ENGINEERING COLLEGE OF LIBERAL ARTS AND SCIENCES UNIVERSITY OF ILLINOIS UNIVERSITY OF ILLINOIS Ua,j c**x 192 THIS IS TO CERTIFY THAT THE THESIS PREPARED UNDER MY SUPERVISION BY Yorie Hcv.^rd Jot:; 2, •,«+■ t J^TTj*jTJ ,J J . Jk. - _ W ... - » o w A *-> • rou±. in Cy.osne anl its Derivative^ IS APPROVED BY ME AS FULFILLING THIS PART OF THE REQUIREMENTS FOR THE DEGREE OF Bachelor of . Vy *- . U- Chemical Engineering 5 ?_ C_c^^vJL_ JL l Instructor in Charge Approv 'ed j£AKEi ■7 CJL HEAD OF DEPARTMENT OF Digitized by the Internet Archive in 2015 https://archive.org/details/artificialmuskssOOjoff ACK1T 0 vVItSDGrBLIEIff T In writing this thesis the author wishes to acknowledge his indebtedness to Doctor Carl S. Marvel, under whose supervision this work was done, for his numerous, invaluable suggestions, for his interest in the work and for his ready willingness to help. TABLE OE CONTENTS Page I. Introduction and Historical -- — ■ 1 II* Theoretical — 3 III. Experimental 10 IV. Summary 17 INTRODUCTION AND HISTORICAL Most of the expensive perfumes are unstable; the fragrance will not last, ^uite accidentlly it was found that a small portion of ’mush' will prevent decomposition and will even increase the strength of the fragrance. LIusks, then, find their chief use in the perfume industries. Natural products which are obtained with difficulty and are expensive always form an incentive towards the preparation of synthetic or artifical products. When one speaks of a syntptie or artifical product one naturally surmises that the synthesized compound has the same composition as the natural product. With artifical musks, however, this does not apply. Natural musks have been studied, yet little is known as to their structure. It has been determined that the active principle is of a ketonic structure and that it contains no nitrogen. The artifical musk is a nitro-derivative of the benzene series and resembles the natural product in odor only. Among the foremost of investigators in synthesizing artifical musks was Albert Bauer. Together with Thurgan he synthesized tri-ni tro-pseudo butyl toluene, tri-nitro pseudo butyl meta 1 2 xylene , methyl ether of tri-nitro oxy pseudo butyl methyl benzene, dinitro tertiary butyl xylyl methyl ketone, methyl ketone of tri- 1. B. 24, 2832-2843 2. B. 27, 1614-1619 . - 2 - < 7 . nitro pseudo butyl toluene and di-nitro tertiary bu.tyl xylyl 4 aldehyde . All of these compound smell strongly of musk. Kis work was followed by many others and numerous patents, both in Germany and France were issued for the preparation of artifical musks . The object of this research is to prepare a product having a strong odor of musk, using cymene as the base; cymene being chosen because of its comparative cheapness. 3. B. 31, 1344-1349 4. B. 32, 3647-3648 THEORETICAL Following along the line of work done by Baur and Thurgan, the methyl ketone of cymene was prepared"* - . In the first runs the yield was very poor but by using a mercury seal stirrer and a three-necked flask, which made possible the introduction of the acetyl chloride slowly, the product was obtained with a yield of 62$. In large runs extreme care had to be exercised because of the large amount of carbon bisulphide used as a solvent. This ketone was then nitrated. For nitration purposes, in synthesizing ketone musks, Baur used 100 $ nitric acid. Although 100 $ acid, as a nitrating agent is not used now.it was thought advisable to make a run using Baur's method. Being unable to obtain the acid its preparation was tried, but the attempt proved unsuccessful. The problem was referred to the research department of the General Chemical Company, but was reported as a failure. This means of nitration had to be given up and instead, 7 $ fuming sulphuric acid followed by fuming nitric acid was used. of The results obtained by nitration 'acetocymene were very A discouraging. All of Baur's compounds possessed a definite cry- stalline form. Acetocymene, however, on nitration came down as a gummy mass, which could not be crystallized from alcohol, petrol- et/m ether, benzene, ethyl acetate or a mixture of ethyl acetate and benzene. The mass was set aside for six weeks and then a crystal- line compound isolated from carbon tetrachloride. It was thought that this compound was a mono or dinitro derivative of acetocymene, 1. Jour, fxir pr. ch. 42, 508 . , , — i3— but tests showed that the compound was an acid, giving a definite neutral equivalent. This fact seemed so out of the ordinary that the preparation of further artifical musks was given up and the determination of the structure of this compound undertaken. The nitration of acetocymene was repeated to obtain the yield of crystalline product. Attempts to isolate a solid from carbon tetrachloride immediately after nitrstion failed. It seemed that some "aging" is required before a separation can be made. In 1920 A If than ^ , a German chemist* studied the nitration products of cymene and toluene. He found that cymene on nitration gave 2,6 din itro cymene and also 2,4 dinitro toluene. In the latter case the iso-propyl group is first oxidized to the acid and then the carboxyl group is replaced by a nitro group. He also found that p-acetfi) toluene upon nitration gave 2,6 dinitro- p toluic acid. The product which was obtained by nitrating acetocymene dissolves in sodium hydroxide and gives a neutral equivalent. From previous work on cymene the following possibilities for its structure suggest themself. I C-OH QN hC^ch 3 J Z68 B. 53B, 178 , ' « * Jig i , -4- All three possibilities contain two nitro groups. The analysis for nitrogen clearly verifies this assumption. The neutral equivalent of 263, that was obtained eliminates formula I. The analysis for C eliminates formula II; formula III then remains. The nitrated product was oxidized using potassium permanganate in alkaline solution as the oxidizing agent. A white ciystalline product melting sharply was obtained. A neutral equivalent was taken which showed the presence of two carboxyl groups. If formula III were correct the oxidation product should be From previous work it has been shown that the isopropyl group is unstable and will be oxidized first. An analysis of the oxidation product showed the presence of only one nitro group and the neutral equivalent and the analysis for carbon did not check with the above formula. The only other possibility is that one nitro group has entered the isopropyl group, which on oxidation was removed. The following structure was assigned to the crystalline product isolated from the nitration of acetocymene. All analysis verify CHj N OH Hf^CH d - — 5— this assumption. The stability of the isopropyl group in all of the previous work was not of the same degree. The author set out, therefore, to determine what properties or conditions were necessary to make the isopropyl group in cymene or its derivatives stable towards the action of the nitrating agent, sulphuric acid-nitric acid. 1 P- cymene treated with chlorine forms monochloro- cymene. This on nitration gives 2- chloro-dinitro cymene. The yield was high, although a small amount of oxidation product was obtained, b 2 Again, when tymol was nitrated , trinitro- thymol was not obtained. Instead, the isopropyl group was removed forming trinitro-m- cresol. Mr- Zellhoefer, of our laboratories, nitrated the methyl ether of "thymol and obtained the methyl ether of tri-nitro- a-cresol . These works as well as the work on cymene led to the belief that the group meta to the isopropyl group had some definite relation to the stability of that group. So many ideas have been set forth that nothing definite has as yet been determined along this line. With these points in view the second* step in V this research was begun. Since the -COOH^ group in acetocymene on nitration was oxidized to the carboxyl group the first step was to prepare o- me thy 1-m- isopropyl benzoic acid from acetocymene. A strong 1. J.Ind. and 3ng. Chem. 11, 1130-1133 2. Chem. News 47, 115 I ■ - 6 - strong oxidiz&ng agent could not be used because of the unstabil ■ ity of the isopropyl group. Directions are given in Noyes laboratory Manual for the oxidation of berjalacetone to cinn- amic acid by using sodium hypochlorite as the oxidizing agent. By following these general directions with the exception that a more concentrated hypochlori te solution was used it was possible to oxidize acetocyrnene to o- me thy 1-m- isopropyl benzoic acid in yields exceeding 75 $• This acid has previously been prepared’ 3 ' by heating tricarvaCrol phosphate with potassium cyanide and then hydrolyzing the product. This reaction is acc omp a n /ed ^by the formation of many impurities which make it much more complicated than the method used above. The acid thus obtained was then nitrated under the same conditions that acetocyrnene was nitrated, A pale yellow compound was obtained which upon recrystallization from 50 $ alcohol came down in very fine needles, clustering to form plates. A mixed melting point with the nitration product of actocymene gave a melting point which was the same as that of the original compound. There is no doubt that the compound obtained from the nitration of acetocyrnene and from the nitra- tion of o-methyl-m-isopropyl benzoic acid are the same. There is, however, a marked difference in the yields of these products, The first was obtained with difficulty with a yield of 15$, while the second was obtained with a yield of 9 £$. Here we have evidence, surely, of a stabilizing action. 1. B. 18, 1714 J _ 1 * * -7- It seems highly probable that the carboxyl group meta to the isopropyl group stabilises that group towards the action of the nitrating agent.