A DECADE of ADVANCE in ORGANIC CHEMICAL MANUFACTURE* WILLIAM J. HALE The Dow Chemical Company, Midland, Michigan
The organic reactions of the textbooks base been superseded by new and entirely different processes i n industry. Catalytic and high-pressure processes h e brought about a reyolution in organic chemical production. Not only hawe new processes displaced old, but new and more complex products are crowding out the ones we previously knew. The chemistry student must know more of what i s actually going on in chemical plants if he i s to be regarded as chemically intelligent.
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T IS WELL, from time to time, that educational leaders consider the scientific progress in our industrial world. Particularly of late has keen competition forced the adoption everywhere of the simplest and most economical of manufacturing steps. Indeed, change from the old order has become the general rule. The teaching of organic chemistry in our schools and universities is well known to lag far behind the state of its art. This discrepancy has come about primarily by reason of the zealous care exercised by industrial laboratories in making their discoveries as secure as possible against encroachment. In a world of approximately two hundred thousand compounds no single patent is likely to secure much to the inventor. The teaching of inorganic chemistry, on the other hand, is much more closely in line with industrial practice. A mere thirty to thirty-five thousand compounds, all falling into distinctive groups of a periodic system, affer littlethat cannot he fairly well covered in early patents. But beneath all this the failure of orcanic chemical instruction to keep abreast of the times lay in a lack of broad chemical training on the part of the instructors themselves. In the early days of this century little attention was given in our universities to organic chemistry. Today it is unfolding magnificently and is indeed "chemistry par excellence." All chemical curricula must be adjusted accordingly. It was not until the first decade of this century that American texts on general chemistry devoted so much as a single chapter to the carbon compounds--chiefly, carbon monoxide and carbon dioxide. In the second
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* Presented before the Division of Chemical Education at the eighty-fifth meeting of the A. C. S.. Washington, D. C., March 28. 1933, as a contribution to the symposium on "Recent DeveloDments in Various Chemical Industries."
decade a university course in general chemistry was made to include a discussion of organic bases, acids, and esters. Today first-year students of chemistry must be inculcated with a wide range of knowledge of organic chemical reactions. Tomorrow first-year students of chemical science must be made familiar not alone with elementary inorganic and organic chemistry but likewise with the principles of that third great branch of chemical science, namely, biochemistry. It becomes, therefore, the duty of those in charge of curricula a t all educational institutions to work constantly toward the elimination of much that is trite and valueless in chemical courses. When thoroughgoing basic chemistry is taught then one can expect to meet college graduates capable of understanding contemporary chemistry in the industrial world. True, those preparing directly for chemical work will have taken a goodly portion of extra instruction in chemical and allied sciences; but the great mass of students, even those with only one year of chemistry, certainly should be classifiable as chemically intelligent even though i t be in minor matters only. Unless a student grasps the import of carbon compounds on this mundane sphere he can have little or no insight into the science of chemistry as a whole and its relations to humanity. Many reactions as described in the organic chemical textbooks of today are altogether obsolete. Historically, of course, these old processes are of interest but in in an advancing science too much time cannot be given to historical considerations. It will suffice here to review the past ten years and to note the outstanding developments in organic chemistry as compiled under the general classifications of aliphatic and aromatic compounds. ALIPHATIC COMPOUNDS
By 1923 the Patart process for hydrogenation of carbon monoxide was in actual operation. This process opened up a vast series of reactions involving the oxides of carbon in reaction with hydrogen or its compounds in the presence of catalysts under pressure. The simple production of methyl alcohol from carbon monoxide and hydrogen has received intensive study in all countries and today most of our methanol arises through this process. The product of the half-way stage in this reaction, namely, formaldehyde, has not as yet attained commercial separation, though production of the more
highly oxidized end-product, formic acid, can be commercially instituted on short notice. An interesting outgrowth of this general process is the reaction of halogenated or hydroxylated hydrocarbons upon carbon monoxide. Thus Dieterle and Eschenbach in 1927 announced the prodnction of benzoyl chloride by the action of carbon monoxide upon chlorobenzene. A great number of patents in this field have been issued and much work at present is under prosecution, looking toward the commercial production not only of benzoyl chloride from chlorobenzene but also of acetyl chloride from methyl chloride. In the case of alcohols the reaction of carbon monoxide upon methyl alcohol as announced by H. Dreyfus in 1927 yields acetic acid directly. So far the higher temperatures and pressures here necessary have not led to particularly good yields in final product. From the foregoing it is quite evident that carbon monoxide holds the key position to the future of organic chemistry. Carbon dioxide will find similar use. Even now it is reported that in certain reactions carbon dioxide without pressure will replace carbon monoxide in processes where pressure has been required. The lower aliphatic hydrocarbons have commanded intensive interest everywhere. Among the saturated derivatives we note that methane by direct chlorination by the Martin process can now be made to yield methyl chloride on an economical scale; a thing practically unattainable ten years ago. Further halogenation of methyl chloride is practical, but we still manufacture carbon tetrachloride from carbon bisulfide. In several parts of the country the halogenation of propane, butane, and pentane is now carried out commercially, and the resulting monohalides are made to yield the corresponding alcohols by hydrolysis. Among the dihalides ethylene bromide and chloride and propylene chloride supply a steady market. Secondary and tertiary butyl alcohols are now made in large quantities from corresponding sources to supply increasing demands. The thermal decomposition of the lower aliphatic hydrocarbons has been the subject of intensive study. Methane, of course, yields ethylene and eventually acetylene before final decomposition. The cracking of ethane from natural gas constitutes one of the two chief sources of commercial ethylene. Propane yields ethylene and methane, while normal butane yields propylene and methane or finally ethylene and methane. Decomposition of propylene takes place in the ueighborhood of 650°, whereas a temperature of somewhat over 1000' is usually required for the decomposition of methane. The second chief source of commercial ethylene arises from the cracking of higher petroleum fractious. It is to the unsaturated lower aliphatic hydrocarbons that many chemists a t present are devoting their studies. The same old process for manufactnring acetylene by the action of water upon calcium carbide is still in vome, - . but certainly it cannot endure much longer. Acetylene thus carries a very high
cost even when credit is taken for all of the possible by-products of the process. With present price ranges this cost of acetylene cannot be considered much less than four cents per pound. The use of acetylene is increasing markedly in the manufacture of halogen addition products, chief of which is trichloroethylene so useful in the extraction of caBein from coffee; acetylene tetrabromide likewise meets with specific uses. The principal use of acetylene today in the chemical manufacturing industry is in the preparation of acetaldehyde, acetic acid, and acetic anhydride. When acetic acid is treated with acetylene in the presence of a mercury catalyst, ethylidene diacetate results and the latter under catalytic decomposition by the Gustave Roy process of 1924 yields acetic anhydride and acetaldehyde, where the latter is inhibited from polymerization. Another procedure, that of Strosacker (1930), operates in this country for the conversion of large quantities of acetylene into acetic acid, but in the form of its sodium salt. An aqueous caustic soda solution under pressure constitutes the hydrating agent. Ethylene also is reported as reacting in similar fashion to give the same end-product. Though numerous patents have been issued covering the high-temperature dehydration of acetic acid to acetic anhydride, and encompassing a wide range of catalysts, they are by no means valuable in comparison with newer and far more interesting dehydrations a t lower temperatures. Ethylene has been meeting with a still greater variety of a~plicationthan acetylene. The old-time reaction of ethylene upon hypochlorous acid to yield ethylene chlorohydrin was carried out extensively in Germany during the World War. In this country to a slight extent during the war, and especially directly after the war, ethylene chlorohydrin was manufactured and hydrolyzed to ethylene glycol but several years elapsed before any interest could be found for this final product. Somewhat later another company took up the work and succeeded in getting ethylene glycol on the market as an anti-freeze for automobile radiators. Then, further, nitroglycol and dinitrodiglycol met with growing use as non-freezing explosives. The production of ethylene glycol has increased through use of many of its derivatives, especially its ethers and esters, such, for example, as the monoethyl ether known as cellosolve, and other such compounds admirably suited as solvents for cellulose esters. We must not overlook here the anhydride of ethylene chlorohydrin itself, which is, of course, P,P'-dichloroethyl ether. This ether has found commercial use (under the name of chlorex) in certain selective extraction processes leading to higher grades of lubricating oils. Ethylene oxide as derived directly from ethylene chlorohydrin has likewise met with a growing demand. Its combination with ammonia to give eventually triethanolamine has afforded the industry a penetrant for other solvents. Azain ethylene oxide is used in the preparation of phenilethyl &oh01 by the Grignard reaction, where it-.is &mpl&yed together with chloro-
benzene and magnesium. As far as is known this is the only commercial application of the Grignard process. Dioxane, or the ring-type structure of dimolecular ethylene oxide, is another distinctly new compound of interesting solvent properties and has come recently into new demand. The hydration of ethylene proceeds nowhere near so easily as does that of acetylene. Many patents covering all manner of methods have been issued in this domain but none so far is preferable over the old-time process of treating ethylene with sulfuric acid to give ethyl hydrogen sulfate, and splitting off ethyl alcohol from the latter by hydrolysis, thus releasing the acid for further use, particularly in the manufacture of ammonium sulfate. The overall yield in ethyl alcohol is fair but this is no longer a deciding factor when the price of the original ethylene is only about one cent per pound. Just a few years back two cents per pound was considered an especially low price for ethylene. The further development of ethylene in commerce promises to be stupendous. The present cost of acetylene in its relation to ethylene is militating against its own progress. Necessity knows no mercy. Acetylene must be made a t a cost not appreciably over twice the cost of ethylene or a t approximately two cents per pound as of today. The work of Franz Fischer and his co-workers on the high-temperature cracking of methane is sufficiently prophetic of such realization. That most interesting tendency toward polymerization among unsaturates is best exemplified by acetylene. According to Mignonac, acetylene under the influence of a silent electric discharge a t low temperature proceeds as far as the trimeric state of which the recently described divinyl acetylene as obtained by Nieuwland, in the action of acetylene upon ammoniated cuprous salt, is a practical illustration. The dimeric form, or vinyl acetylene, has been shown by Carothers to take up hydrogen chloride readily and yield 2-chlorobutadiene, or chloroprene, analogous in structure to isoprene (in which the methyl group of the latter is replaced by a chlorine atom in chloroprene). Chloroprene readily polymerizes to a synthetic rubber called duprene, a product possessing excellent elastic properties coupled with high resistance to oils. Commercial production of these acetylene polymers is now under way and meeting with increasing application. The polymeric divinylacetylene is known as synthetic drying oil, which is a chemically resistant lacquer. These rapid developments among the aliphatic unsaturates have actually threatened some of the best known and established of natural processes. Thus, ethyl alcohol from ethylene has threatened the millenium-old fermentation of monosaccharides to alcohol. The Weizmann process for special fermentation of starch into n-butyl alcohol and acetone is even now threatened by synthetic butanol. The organic chemist of vision entertains no fear for the natural sources of such well-known compounds. When ethylene is given away free the cost of ethyl
alcohol from such source can never drop below its cost through fermentation of waste carbohydrates where bacteria and enzymes labor without pay. At present the approximate over-all manufacturing cost of ethyl alcohol from either source is from twelve to fifteen cents per gallon, or slightly more than two cents per pound of 100% ethyl alcohol. Even this is entirely too high as the organic diagnostician can readily envisage. When acetaldehyde undergoes the well-known aldol condensation to crotonaldehyde and this in turn is reduced, we come to the commercial synthetic process for n-butyl alcohol now in operation. Needless to say, butyl alcohol by fermentation will always hold the advantage over the synthetic product so long as there is abundant use of the by-product, acetone; but again the growing dqmnds for ethyl acetate now producible in large measure by the Zeisberg process of 1927which is a Cannizzaro reaction involving two molecules of acetaldehyde originating in situ from ethyl alcoholmay a t times shift the advantage to the side of ethyl alcohol source, because in this latter process n-butyl alcohol is obtained as a by-product. Among alkyl metal compounds the introduction of tetraethyllead is an example of a former curiosity attaining large commercial prodnction; here by reason of its serviceability in reducing knock in internal combustion motors. Though the action of sodium-lead alloy upon ethyl chloride constitutes the general method for its preparation, i t is interesting to know that the Grignard reaction may serve admirably and economically to the same end. In the field of carbohydrates a world of possibilities lies before us. The degradation of starch into glucose has attained huge proportions in this country. In the fermentation industries mention must be made of the commercial prodnction of glycerin in large quantities by the alkaline fermentation of sucrose. Citric acid also is produced commercially by enzymatic action of fungi upon glucose. The reduction of the carboxyl groups of aliphatic acids to produce the corresponding alcohols has long occupied the attention of chemists. Only of late have we attained that end commercially. This reduction is found by Schrauth (1928) to proceed under the influence of mild debydrogenative (hydrogenative) catalysts in the presence of activating agents and under a pressure of about 200 atmospheres below 350°. When esters of unsaturated higher aliphatic acids are employed hydrogenation takes effect also a t points of unsaturation. By treatment of these higher aliphatic alcohols with sulfuric acid there are formed the monoalkyl sulfuric esters which display such excellent detergent properties. The sodium salts of these sulfuric esters are now displacing old-fashioned soaps in use with lime or hard water-the organic alcohol radical is not precipitable by metallic ions. In the simple hydrolysis of sucrose we are now obtaining in a small way marketable quantities of levulose so much desired by diabetic patients. This process is to be increased this summer to produce five hundred
pounds of levulose per day and soon the commercial production of other monosaccharides will follow. Cellulose is meeting with greater and greater diversification in the production of artificial silk-like fibers and in various types of ethers and esters. Possibly cellulose acetopropionate offers the best lead in many years. In this connection mention should he made of the dehydration of certain pentoses into furfural; oat hulls constituting here the chief source of supply. Furfural as an aldehyde of the furane group is adaptable to many commercial organic processes where formerly the simpler formaldehyde found use. The ring splitting of furfural, accompanied by oxidation, may easily afford a low-priced succinic acid when need for this acid attains large proportions. Among the terpenes and related compounds synthetic camphor stands out as of greatest import. This synthesis however takes as its starting point the or-pinene component of our oil of turpentine. Though begun in a large way some time ago its manufacture in America has just been revived. When we include the element nitrogen in aliphatic structures we shall need to mention particularly the reaction of carbon dioxide upon ammonia to yield urea. This process is now operating successfully in this country. It constitutes a large factor in the fertilizer industry. Again in a small way the basic protein glycine, or amino acetic acid, is under daily production. It is prepared by the ammonolysis of chloroacetic acid. Its use in feeding to patients lacking proper muscular development is meeting with phenomenal success. AROMATIC SERIES
The counterpart of pyrogenic processes on aliphatic hydrocarbons is represented by the commercial production of xenene (formerly called diphenyl) direct from benzene. It is advisable here that no metal whatever come in contact with the heated benzene vapors. The cost of finished xenene to the manufacturer does not exceed twice the price of the benzene. The halogenation of benzene has proceeded in such a measure that one of the by-products, hydrochloric acid, has found here its principal commercial source. The chief by-product, paradichlorobenzene, is meeting with increasing use as a deodorant and insecticide. In the halogenation of xenene a wide range of chloroxenenes result, a number of which now find steady production and serve particularly as dielectric media. The alkali hydrolysis of monochlorohenzene by the Hale-Britton process bas commanded ever-increasing attention. This process requires the passage of chlorobenzene and dilute aqueous caustic soda solution containing a definite quantity of diphenyl oxide through a continuous tubular system a t five thousand pounds pressure and a t about 360°C. During a thirty-minute passage the hydrolysis is complete. Since the reaction is exothermal, use of heat interchangers practically obviates t h e necessity of external heating. Direct hydrolysis of chlorobenzene, bromobenzene, and iodo-
benzene by water vapor alone requires an equally high temperature for each and is productive of poor yields and much loss of material. Theoretically this aqueous vapor hydrolysis of benzene halide should be ideal. Though many patents have been taken out to cover a wide range of such procedures none is commercially operative. The next step forward in hydrolysis of chlorobenzene will undoubtedly comprehend the initial formation of diphenyl oxide by the action of lime water upon the benzene halide and the subsequent hydration of the diphenyl oxide by weak alkaline solution such as sodium phenate by which the diphenyl oxide is directly converted to free pheuol. The cost of phenol from chlorobenzene is possibly twenty to twenty-five per cent less than its cost by the sulfonation process. In fact there is only one remaining plant in this country operating by the old-fashioned sulfouation process; such operation is continued by reason of a considerable demand a t present for the by-product, sodium sulfite. In addition to a good yield of phenol through alkaline hydrolysis of chlorobenzene there is simultaneously obtained a small quantity of ortho and para hydroxyxenene, i. e., ortho and para xenols (formerly known as ortho and para phenylphenols). The quantity of these xenols can be increased in ratio to the phenol but not materially so. As these new phenols now are meeting with such intensive interest and diverse adaptations i t has become necessary to install special additional manufacturing units for each of them. Thus, when xenene itself is chlorinated and put through low-temperature hydrolysis we obtain, of course, high yields of the corresponding xenols. Ortho xenol today occupies that position in the pharmaceutical industry which phenol held some twenty years ago. It is thirty-eight times more powerful than phenol as against standard bacilli. It is odorless, tasteless, and absolutely non-toxic to man. The use of ortho xenol, now manufactured to the extent of thousands of pounds daily, is advancing by leaps and bounds. Para xenol likewise is finding increasing use in the plastic and dye industry. In plastics in particular i t leads to finished products notably resistant to high temperatures and hot water. The co-pr6duct in the modern phenol process is diphenyl oxide but its formation, of course, is under perfect control. However, this highly inert compound is sold not alone as a geranium perfume but primarily as a heat-transfer agent. In this latter domain a mixture of diphenyl oxide with small quantities of xenene is found to possess excellent merit. A new side reaction in the modern production of phenol may later be developed to yield ortho phenyldiphenyl oxide or ortho phenoxyxenene of very high boiling point, undoubtedly serviceable likewise as a heat-transfer agent. Furthermore the commercial reduction of phenol to cyclohexanol is affording us a solvent of unusual properties and one which is meeting with use in certain refining processes. It is interesting to note that the reduction products of the xenols furnish still further in-
teresting types of solvents-particularly a t the halfway reduction stage known as cyclohexyl phenols. The reduction of benzene itself into cyclohexane is in small production; the oxidation of benzene into maleic acid by the Weiss and Downs process of 1920 has only lately come into commercial possibilities. The hydration of maleic acid is now made to yield malic acid. Fumaric acid, the isomer of maleic acid, has become the source of most of our succinic acid by the Noms process involving electrolytic reduction. Maleic acid can likewise be used to this end, but in this case the introduction of a diaphragm, with higher cost, is involved. The manufacture of anthraquinone of high purity by the Gustav Heller process, namely, the action of phthalic anhydride on benzene in the presence of aluminum chloride, has attained large proportions. Certain derivatives of anthraquinone have lately been prepared by the same general process. Former difficulties in the purification of commercial anthraquinone have thus been entirely obviated. The ammonolysis of chlorobenzene to aniline by the Hale-Britton process, employing aqueous ammonia under eight hundred pounds pressure and in the presence of specially prepared catalysts, has resulted in placing on the market a quality of aniline well-nigh unobtainable by any other process. The co-products in this new process are diphenylamine and phenol. The latter, of course, is in demand but diphenylamine itself, though its production here is held under perfect control, has not met with any extensive use. When new uses for diphenylamine arise, such that thousands of tons may be required, then its procurement is assured at a price practically equivalent to that of aniline. This superior aniline by the new process costs considerably less than that prepared by the cumbersome and troublesome benzene nitration and reduction; even less than when the nitric acid component of expense in the old-time nitration method is considered nil. Among the dyes there has grown up an increasing demand for the naphthol AS class. A large number of such dyes, anilides of oxynaphthoic acid, are now manu-
factured and developed as such on the textile fibers. For rayon silk the disazo class is chidy in use and particularly those containing metallic elements in the molecule. When compounds of the naphthol AS type are mixed with diazotized bases they yield the wellknown Rapid Fast dyes, and when mixed with stabilized aromatic compounds they lead to the recently announced and highly valuable Rapidogens. An interesting class of new vat dyes take their rise in polycarboxynaphthalenes. Throughout the dye industry a much more extensive adaptation of higher and more stable counterparts of the former intermediates is now the rule. Among perfumes and pharmaceuticals a vast array of newly discovered compounds is in use. Hexylresorcinol is illustrative of the advance in chemical structure looking to more efficient antiseptics. Just recently the manufacture of pyridium, or phenylazo-c,c-diaminopyridine, has given us a new type of internal urinary antiseptic. New barbituric acid derivatives, especially, have come to the fore. Among salicylic acid derivatives none is more promising than salicylic ethyl carbonate which offers all the advantages of aspirin without the deleterious effects attributed to the latter. In anesthesia the introduction of divinyl ether is making steady progress; it is not only more rapid than ordinary ether in its effect but scarcely one-fifth as much need be employed. To this general field which comprises production in lesser quantities it is impossible in this brief space to give proper attention. Such discussions belong rather to a study of organic chemicals in medicine and the arts. The processes already enumerated as actually in operation are sufficiently suggestive of whatever criticism is needed in university instruction in organic chemistry. Contraty to the old-fashioned tenets of the textbooks even of today, let it be emphasized that ethyl acetate need not be made from acetic acid; benzene halides are easily hydrolyzed; sugars were never intended as foods alone. In general, we may conclude that many of the organic chemical compounds of a generation ago must now give way to their more complex counterparts.
