Jaime Wisniak Department of Chemical Engineering , Ben - Gurion University of the Negev , Beer - Sheva , Israel 84105

Thomas Anderson (1819-1874), a physician turned chemist, did most of his research in organic chemistry. He discovered butylamine, collidine, lutidine, picoline, and pyridine during the pyrolysis of coal and destruction of bone oil, studied the constitution of anthracene, piperidine, and codeine; the analysis and properties of alkaloids derived from opium, and prepared a large number of new derivatives of these organic bases. LIFE AND CAREER Thomas Anderson, born at Leith, Scotland, in July 2, 1819, was the eldest of the nine children of Charles Anderson (1772–1855), a practicing surgeon, and Mary Rhind. After taking his classical education at the high school of Leith and the Edinburgh Academy, he entered the University of Edinburgh as a medical student. Here he was the first to obtain (1839-40) the biennial prize instituted by Thomas Hope (1766-1844), the chemistry professor, for an essay on the compounds of carbon and hydrogen. Anderson graduated M.D. in 1841, with a thesis On the Nature of the Chemical Changes, which take place in Secretion, Nutrition, and the other Functions of Living Beings. Feeling that his knowledge of organic chemistry was lacking, he continued his studies in Stockholm under Jöns Jacob Berzelius (1779-1848) (1842) and then at Giesen, Germany, under the guidance of Justus von Liebig (1803-1883) (1843). Before returning to Edinburgh he visited the laboratories of other distinguished chemists in Bonn, Berlin, and Vienna. Once in Edinburgh he was appointed lecturer at the extra-mural school of medicine and surgery, which qualified students for examination by the Royal College of Surgeons and other medical corporations (1846). In 1845 he was elected fellow of the Royal Society of Edinburgh, and in 1848, he became the first chemist hired by the Highland and Agricultural Society of Scotland, taking over the services previously provided by James Finlay Weir Johnston (17961855). Anderson kept this position until a short time of his death. In 1852, after the death of Thomas Thomson (17731852), he was appointed Regius Professor of Chemistry at the University of Glasgow, and remained in that post for the rest of his career. This position gave him a secure job, and allowed him to marry Mary Barclay on the same year. Over the next four years they had three sons, two of whom survived him. Anderson received many honors and awards for his scientific achievements. In 1854, he became editor of the Edinburgh New Philosophical Journal; in 1859, he was elected president of the Glasgow Philosophical Society and in 1867, president of the chemical section of the British Association for the Advancement of Science. The Royal Society of Edinburgh awarded him twice the Keith medal, in 1853 for his papers on The Products of the Destructive Jaime Wisniak Department of Chemical Engineering, Ben-Gurion University of the Negev,Beer-Sheva, Israel 84105 [email protected] Revista CENIC Ciencias Químicas, Vol. 45, pp. 148-159, 2014. 149 Distillation of Animal Substances; and in 1855 for his memoirs on The Crystalline Constituents of Opium. In 1872, the Royal Society of London awarded him a Royal medal "for his investigations on the organic bases of Dippel’s animal oil; on codeine; on the crystallized constituents of opium; on piperidine and on papaverine; and for his researches in physiological and agricultural chemistry" [1] Anderson was an honorary member of the Royal Academy of Sciences of Uppsala, and received a DCL of Nova Scotia, and an LLD of Glasgow (1874). In 1869, Anderson suffered a stroke and spent the last part of his life in mental and physical suffering, probably caused by syphilis; as a consequence, he resigned from the Agricultural Society in 1873, and in 1874 from the Glasgow chair. He passed away on November 2, 1874, and was buried in St Nicholas's churchyard, Chiswick. Anderson carried on research in inorganic chemistry, organic chemistry, and agricultural subjects. His first publications were on new mineral species and on the atomic mass of nitrogen (the last one probably done during his stay with Berzelius). He then carried on an exhaustive investigation of the pyrolysis of coal tar and the destructive distillation of animal substances, particularly bone oil. These led him to determine the structure of anthracene and the discovery of petinine (butylamine), picoline, lutidine, collidine, and a series of members of the ammonia and aniline series. He isolated the coloring matter present in Indian mulberry and kamala, studied action of sulfur on some vegetable oils, and did extensive work on the structure of codeine and the composition, formula, reactions, and salts of a series of alkaloids. His work as a chemist for the Highland Society led to the analysis of many important agricultural materials, such as plant ashes, oil cakes, soils, feeding stuffs, fertilizers and manures made in England and abroad, and sewage. He published a textbook, Elements of Agricultural Chemistry, 7 reflecting his findings and the state of the art at his time. SCIENTIFIC CONTRIBUTION Anderson published near 30 papers on chemical subjects and more than 100 reports of different agricultural subjects. A list of most of the latter may be found in the Index for the First, Second, and Third Series of the Transactions of the Highland and Agricultural Society of Scotland, from 1799 to 1865, published in Edinburgh in 1869. Here we summarize most of his works in mineral and organic chemistry. When reading Anderson’s conclusions regarding the formula of the components he studied, care should be taken to realize that he is using the values of atomic masses prevalent in his days, not the modern ones. Thus, for example, for him, the atomic masses of carbon, hydrogen, and oxygen, were 150, 6.25, and 17.5, respectively. Vegetable dyes Indian mulberry (Morinda citrifolia) According to Anderson, the roots of the plant Morinda citrifolia (Indian mulberry) was imported, under the name of Sooranjee from Bombay, India, into Glasgow, as a possible substitute of the red dye obtained from madder (Rubia tinctorum). Although some of Glasgow’s experienced calico printers had declared that these roots had not dyeing capability at all, Professor Stewart Balfour (1828-1887) of Owens College asked Anderson to carry on a detailed chemical analysis of the roots of Morinda. Anderson reported that the bark of the roots had an external grayish brown color, but when broken across it presented colors varying from fine yellow to brownish red. The wood was colored red by alkalis indicating the presence of a certain quantity of coloring matter into it. Boiled with water it gave a wine-yellow decoction, and with alcohol a deep red tincture. Anderson found that although the coloring matter, which he named morindine, was very soluble in boiling water; the decoction also contained a viscous matter, which complicated the filtration; for this reason he resorted to alcoholic extraction. The powdered bark of the root was boiled with six times its weight of rectified alcohol and the resulting deep brown-red tincture filtered while hot. On cooling, it deposited a brown flocculent precipitate, consisting of morindine and some red coloring matter. The process was repeated several times yielding morindine gradually purer, and at last it appeared as small yellow crystals. It was purified by crystallization, first from alcohol of 50 %, and then from alcohol slightly acidified with HCl (to remove any inorganic substances). Morindine crystallized from its alcoholic solution in small, concentrically grouped soft needles, which when dried and pressed together, formed a sulfur yellow mass, of satin luster. These crystals were slightly soluble in cold, but more soluble in hot alcohol (particularly when dilute); they were slightly soluble in absolute alcohol and totally insoluble in ether. They dissolved in alkalis and in concentrated sulfuric acid, producing an orange red or a deep purple solution, respectively. An aqueous solution of morindine reacted with salts, (e.g. lead sub-acetate, strontia, baryta, limewater, ferric chloride, alum, etc.), producing precipitates of different colors. Heated in a closed vessel, morindine melted into a deep brown liquid, which boiled at a high temperature, and afterwards released orange vapors of a substance, analogous to those of NO2, which deposited as oblong red needles, and leaving a carbonaceous residue in the vessel. Anderson named the sublimable substance morindone. Elemental analysis indicated that morindine contained 55.46 % carbon, 5.19 % hydrogen, and 39.35 % oxygen, corresponding to the overall formula C28H15O15. Anderson remarked that this formula differed from that of sublimed madder purple (C28H16O16) by one equivalent of water. Revista CENIC Ciencias Químicas, Vol. 45, pp. 148-159, 2014. 150 Anderson found that although morindine was unable to produce a color with common mordants, such alum an iron, it did with a cloth mordanted for Turkey red (a material made from the roots of Rubia). The resulting dark brownish red hue was perfectly fixed. Anderson also studied the properties of morindone and reported that it was insoluble in cold or hot water, easily soluble in alcohol and ether, and that alkalis and concentrated sulfuric acid dissolved it with a violet color. Its ammoniacal solution yielded with a solution of alum, a red precipitate, and with baryta water, a cobalt blue one. Elemental analysis indicated that it contained 65.81 % carbon, 4.18 % hydrogen, and 30.01 % oxygen, corresponding to the overall formula C28H10O10. Morindone was found to be a true coloring matter, capable of attaching itself to common mordants. With alumina it furnished a deep rose-red, and with iron violet and black. Kamala (Rottlera tinctoria) In another paper, Anderson reported the properties and analysis of the coloring matter of kamala, a large tree growing in most of the Indian peninsula. Its fruit is covered with hairs and red glands, easily separated by rubbing and forming a uniform red brick dust colored powder, which repels water and his sparingly soluble in it. Anderson found that the red coloring matter was easily soluble in alcohol, ether, alkalis, and their carbonates. A proximate analysis showed that it contained 78.19 % resinous coloring matters, 3.49 % water, 7.34 % albuminous matters, 7.14 % cellulose and other wood materials, and 3.84 % ash. The coloring matter was found to consist of at least three different substances: (1) rottlerine, a crystallizable matter, extracted by ether, forming yellow crystalline scales, insoluble in water, slightly soluble in alcohol, and very soluble in ether. It dissolved in alkaline solutions with a deep red color but did not form definite compounds with metallic oxides. Elemental analysis indicated that it contained 69.112 % carbon, 5.550 % hydrogen, and 25.333 % oxygen; (2) A pale flocky amorphous substance, obtained by cooling of a hot alcohol extract of the coloring matter. This substance was insoluble in water, soluble in hot alcohol, and sparingly soluble in cold alcohol and ether. Its elemental analysis corresponded to the formula C40H34O8; and (3) a dark red amorphous resin separated by evaporation from the mother liquor of the flocky substance, melting at 100 C and having as formula C60H30O14. Anderson reported that the coloring matter of Rottlera was a substantive dye, which did not require the intervention of a mordant. It gaves a fine flame color on silk and a pale fawn color to silk (with or without mordant). Action of sulfur on fixed oils In a paper published in 1847, Anderson wrote that many chemical reactions had been used as agents to determine the composition of a given substance. The products of the decomposition of a substance varied according to the conditions of the experiment and the nature of the chemical used to carry it on. Some agents, such as the halogens and ammonia, not only eliminated one or more substances from the original one, but also combined with the residual atoms, forming a new derivative of the original compound. The halogens acted on the hydrogen present in the compound while ammonia did it on the oxygen. These considerations led Anderson to investigate the nature of the action of pure sulfur upon organic compounds. To his knowledge, this subject had not been researched at all, except for a paper from William Christian Zeise (1789-1847). In 1842, Zeise had reported that when adding pure finely divided sulfur to an ammonia solution in dry acetone, a considerable amount of sulfur dissolved, forming a clear green liquid, which soon became brownish yellow and then coffee brown. Addition of more ammonia turned the solution into a reddish brown syrupy mass, strongly alkaline, and smelling as hydrogen sulfide. According to Zeise, the ammonia decomposed in such a manner that the nitrogen and hydrogen divided between the sulfur, and the carbon, hydrogen, and oxygen of acetone. From the final complex mass, Zeise separated several substances, which he named thakcetone, akcethine, melathine, therythrine, and elathine, and gave their properties but not their composition. Initially, Anderson examined the action of sulfur upon some simple organic compounds, with disappointing results. For this reason he decided to study the reaction of sulfur with fixed oils, for which sulfur was known to act (e.g. olive oil). He remarked that on heating the mixture of fixed oil and sulfur in a retort, the sulfur melted and formed a liquid layer at the bottom of the oil. At a higher temperature it dissolved forming a thick dark red viscous liquid; afterwards, a violent reaction took place accompanied by swelling of the mass and release of H2S. More heating resulting in the passing over to the receiver of an oily substance smelling like garlic. In order to interpret these results, Anderson decided to study the action of sulfur upon de components of the fixed oil. Reaction of sulfur with stearic acid showed that no particular products were produced; there was a slight release of H2S and the products were identical with those obtained from the pure oil. Hence, he deduced that the smelly oils produced from olive oil originated from the reaction of sulfur with the oleic acid or with the glycerin. Reaction of sulfur with pure oleic acid led to the formation of products similar to the ones obtained with olive oil. Anderson reported that although he could not obtain enough glycerin to study it separately, he had not noticed the presence of acrolein during the distillation of the oil with sulfur. The product of the distillation of oleic acid was nauseous reddish brown oil, from which the dissolved H2S was eliminated by rectification. The first fractions that distilled were transparent and colorless; the following ones became Revista CENIC Ciencias Químicas, Vol. 45, pp. 148-159, 2014. 151 gradually darker in color, and the last ones became semisolid on standing while depositing white crystalline plates. The crystals were separated and purified by recrystallization from alcohol. Their properties and analysis indicated they were margaric acid, C34H34O4 (heptadecanoic acid, C17H34O2, with the present value of atomic masses). Anderson remarked that the oil that distilled before and together with margaric acid constituted the most abundant product of the reaction of sulfur upon olive oil, linseed oil, and almond oil, and was a very complex substance. With mercuric chloride it yielded a bulky white precipitate, and with platinum dichloride, a yellow compound. Boiling an alcoholic solution of the oil with silver nitrate or lead acetate resulted in the precipitation of the corresponding sulfides. The elemental analysis of the precipitate produced with mercuric chloride corresponded to the formula C16H16S5Hg4Cl2; Anderson remarked that he did not believe that this formula represented the rational one of the compound. The remarkable analogy between its properties and those of the mercury compound of allyl sulfide suggested a similarity in their chemical constitution: Anderson suggested that its actual formula was C8H8S2 and named it odmyl. A similar analysis of the platinum precipitate did not give a precise result; nevertheless, Anderson believed that it also contained odmyl, probably mixed with platinum sulfide. Destructive distillation Picoline In 1834, Friedlieb Ferdinand Runge (1795-1867) published a paper about the products of the destructive distillation of coal where he reported the formation of about 20 different substances; three of them had acid behavior and three were bases. To the later he gave the names kyanol (blue oil, today, aniline), leucol (today, quinoline), and pyrrole, from the peculiar colors developed by the action of certain reagents on their salts (for example, kyanol turned blue when treated with calcium chloride, and pyrrole turned red fir wood moistened with HCl). In 1846, Anderson announced that examination of the mixed bases contained in coal tar had led him to discover a new base, which he proposed naming picoline. The starting material was prepared by a modification of Runge’s procedure, which Anderson described as follows: In the preparation of naphtha from coal tar, the first product of distillation was normally agitated with sulfuric acid with the purpose of eliminating naphthalene and other substances which made crude naphtha to become dark colored when exposed to air. The sulfuric acid was then neutralized with ammonia and the mixture distilled. The basic compounds neutralized by the acid were the first ones to pass over as very dark viscous oil, having a pungent and disagreeable odor. Analysis of this oil showed the presence of picoline, pyrrole, aniline, an oily base possessing the properties of quinoline, and heavy oil not showing basic properties. The new base was separated by careful distillation of this oily phase, accompanied by treatments with sulfuric acid, neutralization with KOH, and additional distillations. Pure picoline was found to distill at 133.3 C. Elemental analysis of picoline indicated that it contained 77.16-77.18 % carbon, 7.77-7.62 % hydrogen, and 15.0715.20 % nitrogen, corresponding to the formula C12H7N (the correct formula is C6H7N, with the accepted atomic mass of carbon and nitrogen). Anderson wrote that picoline was a colorless transparent and highly volatile liquid, having a powerful penetrating aromatic smell and acrid taste; it boiled a 133.3 C and did not darken in contact with air. It was completely soluble in water, insoluble in a solution of KOH and most alkaline salts; it dissolved rapidly in alcohol, ether, methanol, and the fixed and volatile oils. It was a powerful alkaline base; a rod dipped in HCl and held over it became immediately surrounded by a copious cloud of picoline hydrochloride. Picoline restored the blue color of reddened litmus paper and did not coagulate the white of egg, as aniline did. Anderson studied the chemical reactions of picoline and found that they were quite different from those of aniline; for example, in contact with a solution of calcium chloride it did not produce the violet color characteristic of aniline. Picoline produced double salts with the chlorides of copper, mercury, platinum, gold, tin, and antimony cupric chloride, and did not precipitate the solutions of silver nitrate, barium or strontium chloride, or magnesium sulfate. Picoline formed with a large number of acids salts, which may could obtained in crystalline form. These salts were highly soluble in water and many of them were soluble in alcohol. Anderson gave a detailed description the method for preparing a variety of salts, as well as their properties (picoline sulfate, oxalate, nitrate, and hydrochloride, and the double chlorides of picoline with platinum and mercury. He also provided details of the products of decomposition of picoline when treated with nitric acid, bromine water, chlorine. Animal substances In the above paper about picoline, Anderson mentioned that the properties of this base recalled those of a base called odorin, obtained Otto Unverdorben (1806-1873) from Dippel’s animal oil (bone oil). According to Unverdorben, bone oil, which was obtained by several successive distillations of hart horns, was a mixture of four bases, which he named odorin, animin, olanin, and ammolin. In order to test his assumption, Anderson treated crude hart horn oil with sulfuric acid and noted that the acid liquid immediately acquired a deep brown reddish color; this phase was separated and when treated with an excess of KOH it deposited a semisolid viscous liquid. The latter, distilled with water, yielded a mixture of several oily bases, which Anderson purified by successive distillations, Revista CENIC Ciencias Químicas, Vol. 45, pp. 148-159, 2014. 152 using a method similar to the one he had employed for picoline. The first fraction that passed (odorin) was colorless oil, which became brown in contact with air; was soluble in water, and its odor was similar to that of picoline. Its properties were similar, but not the same as those of picoline; it boiled at about 100 F and its salts were oleaginous compounds, which distilled in the form of an oily liquid, while the same salts of picoline were mostly crystallizable. These observations led Anderson to carry on a detailed study of the products of the destructive distillation of animal substances. Since hart horn oil had long ceased to be employed, he decided to use commercial bone oil instead. This oil was prepared on the large scale by the distillation of bones in iron cylinders. Bone oil did no differ from true hart horn oil; both were the product of the decomposition of gelatinous tissue only. The commercial material had brown black color, specific gravity 0.970, and a very disagreeable odor. In his first memoir, Anderson reported that he had separated the bases present in hart horn oil by mixing it with dilute sulfuric acid and separating the acid phase, which contained the bases, a certain quantity of non-basic oil, and pyrrole. This solution was mixed with additional sulfuric acid and distilled in a glass retort; the first fraction that passed over contained the water and all the pyrrole; the other bases were retained in a dark brown fluid remaining in the retort. The latter was neutralized with an excess of KOH and distilled again; the first fraction was a colorless watery fluid, which contained all the bases. This liquid was treated with more KOH to separate from it the oily bases. According to Anderson, the product of this operation was extremely complex and consisted of four or five different bases and ammonia. It was now separated by fractional distillation; ammonia was the first material to pass over, and fractions were collected in the temperature ranges 71.1 C-100 C, 115.6 C -121.1 C, and 132.2 C137.8 C. These initial three fractions were found to dissolve completely in water; the following one floated on the surface of water and only dissolved when agitated with a large amount of water. The distillation was continued up to 179.4 C; at this level a drop of the residue added to a solution of calcium chloride immediately gave the reaction of aniline. Analysis of the residue showed that it consisted chiefly of aniline. Each of the fractions collected was again distilled by fractionation to separate the pertinent bases. Anderson studied in detail only the fraction boiling at about 132.2 C. Anderson named the base thus separated petinine, in allusion to his volatility. The amount separated was extremely small, a restriction that allowed him to determine only its composition and the properties of a few of its compounds. Elemental analysis of petinine indicated that it contained 66.66 % carbon, 13.97 % hydrogen, and 19.37 % nitrogen, corresponding to the formula C8H10N. Petinine was a transparent colorless fluid, possessing a high refracting power, a very pungent odor, and taste, and boiling at about 79.4 C. Petinine was a very powerful base and immediately restored the blue color of reddened litmus; it dissolved completely in water, alcohol, ether, and fixed and volatile oils. It reacted with mercuric chloride and platinum dichloride to give double salts. Anderson provided details of the preparation method and properties of petinine sulfate, nitrate, and hydrochloride, as well as the double salts of petinine with platinum and mercury. He concluded his paper reporting that he had found picoline in the fraction boiling between 132.2 C and 137.8 C. In the following paper, Anderson remarked that the need to increase the quantity of active materials retrieved from the raw bone oil had forced him to request from an outside factory to manufacture the oil required for his experiments. Repeating now the same previous processes led him to note that a very powerful and pungent odor was evolved when the fluid began to boil, and that the vapors presented the characteristic reaction of pyrrole. In these circumstances, he connected the head of the distillation retort to a condenser to recover this new substance. The fluid, which distilled over carried with it a small quantity of oil, which proved to be a mixture with oil insoluble in acids. Analysis of the same showed that it was composed of a small amount of the crude oil mixed with a series of bass of remarkable properties; Anderson named them pyrrole bases. The fluid that remained in the retort proved to contain a substance, which was separated as its platinum salt. Elemental analysis indicated that it contained carbon, hydrogen, and nitrogen in the proportion of methylamine. Further separation and analysis of the other fractions showed the presence of propylamine. The occurrence of all these bases allowed Anderson to determine that the constitution of petinine corresponded to the formula C8H11N, that is, petinine was actually butylamine. The next series of experiments was devoted to the separation of the bases boiling above 115.6 C; again by successive fractional distillations (seven times). These experiments led him to discover the existence of two new substances belonging to the same series as the previous ones. From the first fraction, boiling at 115.6 C, he separated a phase, which he named pyridine. Pyridine was a transparent and colorless liquid, which did not become colored in contact with air. It was completely soluble in water and the fixed and volatile oils; it dissolved in the concentrated acids with release of heat and the formation of very soluble salts. An elemental analysis indicated that its composition corresponded to the formula C10H5N (using the old set of atomic masses). From the fraction boiling above 154.4 C Anderson separated another base having the same constitution of toluidine, and which he named lutidine. This base was less soluble in water, floating in it. Its smell was less pungent and more aromatic than picoline; it combined with the acids forming highly soluble salts. Anderson concluded that bone oil contained two series of bases, one that was analogous with ammonia (methylamine, propylamine, etc.), the other a series peculiar to that oil, homologous with one another, and remarkable for their isomerism with the series having aniline as their type (pyridine, picoline, and lutidine). Revista CENIC Ciencias Químicas, Vol. 45, pp. 148-159, 2014. 153 In his third paper on the subject, Anderson wrote that further experiments showed that the series of members having aniline as their type, present in bone oil, did not end in lutidine, but additional bases of higher molecular mass and boiling point were also present in it. He now directed his attention to the portion of bases boiling about 171.1 C. He was unable to separate the additional bases by fractional distillation or their conversion to oxalates followed by factional crystallization because every fraction collected contained aniline in high percentages. For this reason he decided to take advantage of his previous finding that the bases of the picoline series were highly resistant to the action of nitric acid, while aniline was destroyed by this reagent. Treatment of the base boiling at 171.1 C with nitric acid resulted on a brisk exothermic reaction; the acid liquor became deep red colored, red fumes were released accompanied by an odor resembling that of bitter almonds, and formation of thick reddish yellow oil deposit, which smelled like nitrobenzene and had many of its properties. The filtrated oil was submitted to repeat fractional distillation, until a rather pure new base was separated, which boiled between 177.8 °C and 180 C. Anderson named this new base collidine. Anderson’s collidine was colorless transparent oil, stable with time, insoluble in water and floating on it (specific gravity 0.921), highly soluble in alcohol, ether, and the volatile and fixed oils, and boiling at 178.9 C. It dissolved in acids, but these, even when added in large excess, did not neutralize them. It precipitated alumina, chromium, zinc, and ferric oxide from their solutions; but gave no precipitate with baryta, limewater, magnesia, manganese, or nickel. Elemental analysis indicated that it contained 78.97-79.22 % carbon, 9.24-9.58 % hydrogen, and 11.20-11.87% nitrogen, corresponding to the formula C15H11N. Collidine salts were for the most part highly soluble and deliquescent, soluble in alcohol but not in water. Anderson also reported the preparation and properties of collidine platinochloride. In the second part of this paper he reported the results of the reaction of pyridine, picoline, and collidine with ethyl iodide and the properties of ethylpicoline, ethylpyridine, ethylcollidine, and their platinochloride and aurochloride. The results proved that picoline and its homologues should be considered as nitrile bases, capable of taking up only one additional ethyl or similar radical, and converting into fixed compounds of the ammonium bases class. Coal naphtha In 1851, Anderson and Williams published a short note showing that spite of the clear differences between the gelatinous tissue of bones, cinchonine, coal, and bituminous shale, the volatile alkaloids produced by their destructive distillation was almost identical, as shown in the following table: Tissue Cinchonine Coal Dorset shale Pyrrole Pyrrole Pyrrole Pyrrole Pyridine Pyridine ....... Pyridine Picoline Picoline Picoline Picoline Lutidine Lutidine Lutidine Lutidine Collidine Collidine Collidine Collidine ..... Quinoline Quinoline Parvoline* Aniline Lepidine** Aniline * Any liquid ptomaines, C9H13N, derived from pyridine and found in decaying fish or meat. ** 4-Methylquinoline. Anderson and Williams proved that by careful fractional distillation of the bases obtained by treatment of the crude naphtha with sulfuric acid, and further distillation of the acid liquid with calcium oxide it was possible to obtain fluids boiling at 116.7 C, 154.4 C, and 173.9 C. These fractions were converted into their platinum salts and then analyzed, and shown to have the components indicated above. Anthracene and derivatives In 1832, Jean-Baptiste André Dumas (1800-1884) announced that with the help of Auguste Laurent (1807-1853) he had succeeded in separating from coal tar, in addition to naphthalene, another compound of carbon and hydrogen, Revista CENIC Ciencias Químicas, Vol. 45, pp. 148-159, 2014. 154 which he had named provisionally paranaphthaline. He reported that the distillation of coal tar afforded four clearly separated fractions. The first one was an oily substance that yielded a large amount of naphthalene; the second fraction was still oily but afforded a mixture of naphthalene and paranaphthalene, easily separated by means of alcohol. The third product was viscous composed mostly of paranaphthalene, accompanied by a viscous matter, hard to eliminate. The last fraction was accompanied by a yellow red substance characteristic of all the final distillations of coal tar. Dumas indicated that paranaphthalene could also be separated from the second fraction by cooling to -10 C; paranaphthalene precipitated as grainy crystals, which were separated by filtration and purified by washing with alcohol. The alcohol dissolved the retained oily substance, as well as naphthalene. The paranaphthalene present in the third and fourth fractions was separated by dissolving these fraction in turpentine and then cooling to -10C, as before. Paranaphthalene was purified by two or three distillations. According to Dumas, paranaphthalene was insoluble in water, sparingly soluble in alcohol and ether, cold or boiling. The best solvent was turpentine. It dissolved in concentrated sulfuric acid producing a green colored solution; it reacted strongly with nitric acid producing abundant nitrous vapors and leaving a sublimable residue. Elemental analysis indicated that paranaphthalene contained carbon and hydrogen in the ratio 5 : 2, that is, the same ratio as in naphthalene. Measurement of the density of the vapor of paranaphthalene led Dumas to conclude that naphthalene and paranaphthalene were isomeric substances. Further work done by Laurent in 1835 referred to the product obtained by the reaction of nitric acid and paranaphthalene. Laurent found that this substance could be easily precipitated and separated by adding water to the acid liquid. The filtrated solid was purified by sublimation; it appeared as white neutral needles, insoluble in water and almost insoluble in boiling alcohol and ether. It was very soluble in cold concentrated sulfuric acid. Laurent named this new compound paranaphtalèse (today anthraquinone) and determined that its composition corresponded to the formula C80H16O4, that is, paranaphthalene (C80H24), where four equivalents of hydrogen have been replaced by four equivalents of oxygen: C80H24 + O8 = C80H16O4 + H8O4. In another paper, Laurent proposed that the name paranaphthalene be changed to anthracene. In a paper published in 1861, Anderson reviewed the little information that was available about the solid compounds of carbon and hydrogen, remarking that with the exception of naphthalene, very little was known about them. He mentioned that not less than five substances said to be polymeric with naphthalene had been described: anthracene, metanaphthalene or restistene, pyrene, and two other substances not yet named, which appeared together with benzene and benzophenone, during the distillation of calcium benzoate. He criticized Laurent’s results on anthracene, remarking that an examination of his experiments showed that they were extremely imperfect and carried on a very small quantity of material; in addition, the formula proposed by Laurent seemed highly improbable. All these facts suggested the need for further investigation. According to Anderson, crude anthracene appeared as a soft yellow mass, not unlike palm oil, but with a greenish tinge and harder consistency. It contained a little naphthalene and a substantial amount of oil with a high boiling point. It was somewhat soluble in alcohol, and more in ether, turpentine, and benzene. Anderson purified anthracene by fractional distillation; the first fractions that passed were pressed to remove the oil, and the last ones redistilled to get rid of the color as much as possible. The purification was completed by repeated crystallization from benzene, or by sublimation. Purified anthracene appeared as colorless scales, odorless and tasteless. It was not volatile at ordinary temperature, but slowly volatilized in the water bath, subliming freely at higher temperature. It melted at 213.3 C, was insoluble in water, little soluble in alcohol, and more in ether, benzene, and the volatile oils. It did not react with alkalis, but dissolved in sulfuric acid, forming a sulfo-acid. It formed substitution products with chlorine and bromine. Anderson described in detail the reactions with nitric acid, bromine, and chlorine, and the properties of the different derivatives he obtained (oxanthracene, dinitroanthracene, anthracenic acid, anthracene tetrabromide, andthracene hexabromide, chloroanthracene, and dichloroanthracene. Elemental analysis of anthracene indicated that it contained 94.16% carbon and 5.85% hydrogen, corresponding to the formula C28H10. Organic alkalis Action of phosphoric acid In 1838, Victor Regnault (1810-1878) published the results of a long study about the composition of organic alkalis. He wrote that most chemists accepted the idea that all organic bases contained, per atom (molecule), two atoms of nitrogen and that, as a result, their saturation capacity was the same as if this nitrogen existed in the state of ammonia combined with a substance that did not neutralize its capacity as a base. Regnault wrote that, nevertheless, a close examination of the series of salts formed by these bases with acids, showed some outstanding anomalies. For these reasons, he decided to carry on a study to determine the elemental composition, formula, and the equivalent value, of most of the known alkaloids, as well as the amount of water contained in the salts they formed with oxyacids (sulfuric, iodic, nitric, phosphoric, oxalic, and acetic). His resulted indicated that all the salts formed by organic bases contained one atom of water, which could not be eliminated without decomposition. Some years later, Edward Chambers Nicholson (1827-1890) published another paper describing the composition of the different compounds formed by the reaction of phosphoric acid with aniline. Nicholson mentioned that Revista CENIC Ciencias Químicas, Vol. 45, pp. 148-159, 2014. 155 according to Regnault, his analysis of strychnine phosphate indicated that it was a compound of one equivalent of phosphoric acid with one equivalent of strychnine and water. Nicholson mentioned that the strychnine phosphate analyzed by Regnault was actually a common phosphate, corresponding to sodium phosphate with one equivalent of fixed base. For this reason he decided to clarify this inconsistency by studying in detail the reaction of phosphoric acid with aniline. He went on to prepare aniline phosphates containing two equivalents of aniline and one of water, and one equivalent of aniline with two equivalents of water, aniline metaphosphate, and aniline pyrophosphate. His results indicated that all the compounds of aniline with phosphoric acid were anhydrous and proved that organic bases behaved with polybasic acids like mineral oxides. Anderson believed that Regnault’s conclusions regarding strychnine phosphate were wrong, and for this reason he decided to carry on additional experiments on the subject. In these experiments he prepared strychnine phosphate with one equivalent of strychnine by digesting at a gentle heat a moderately dilute solution of tribasic phosphoric acid and strychnine. On cooling, this salt was deposited as long radiated needles, which were acid to test paper and extremely bitter to the taste. Its elemental composition was found to correspond to the formula (C44H23N2O4HO)2HO,PO5. Heated to 260 C the salt lost four equivalents of water and changed to (C44H23N2O4HO)2HO,PO5 + 4H2O. Strychnine phosphate with two equivalents of strychnine was prepared similarly, using an excess of strychnine. Its analysis corresponded to the formula 2(C44H23N2O4HO).HO,PO5 + 18H2O. According to Anderson, the above analysis were sufficient to prove that the phosphates of strychnine agreed in constitution with the inorganic salts of the acid, and enabled to explain the source of error in Regnault’s results. Regnault’s elemental analysis indicated that strychnine phosphate contained 59.85 % of carbon and 5.85 % of hydrogen, so that the excess in carbon content was clearly due to his having analyzed the acid phosphate mixed with a small amount of the last described salt. As a further justification of his conclusions, Anderson prepared the phosphates of brucine with two equivalents of brucine and of quinine with three equivalents of quinine. His analysis of all these salts were enough to ascertain in a suitable way the structure of the phosphates of organic alkalis and to show that they agreed with the inorganic salts of phosphoric acid, as was well as confirm the correctness of Nicholson’s results. As stated by Anderson, if three portions of phosphoric acid were taken and reacted under similar conditions with quinine, brucine, and strychnine, three, two, and one equivalent of the respective bases would react. Quinine, which replaced at once three equivalents of water, could be compared to lead oxide, or the oxides of heavy metals; brucine would represent the organic alkalis, which replace two equivalents in their normal compound, while strychnine, which under ordinary replaced only one equivalent of water, belonged to a class having no analogue among the series of inorganic bases. Oxidation In 1850, Anderson wrote that during his researches on codeine he had noticed the remarkable effects that nitric acid had on this substance, which seemed to be common to all organic bases. Treating codeine with diluted nitric acid generated nitrocodeine, a substituted base, but it if the acid was concentrated, a violent reaction took place accompanied by the release of nitrous vapors and the formation of an orange solution. Addition of water to the latter precipitated a resinous acid. When the nitric solution was evaporated in a water bath, the acid appeared as a yellow porous mass, easily soluble in alcohol. Addition of water to the alcoholic extract reprecipitated the acid; Anderson indicated that although he had not analyzed this acid, it seemed to be an acid derived from codeine by substitution of NO4, and addition of several equivalents of oxygen. The acid dissolved in a diluted solution of KOH; the solution, heated to boiling, released a base having a strong odor. Condensation of the vapors produced a liquid having a penetrating putrid odor and releasing a white vapor when in contact with a glass rod wet with HCl. Saturation of the solution with HCl, followed by evaporation in a water bath, deposited a very crystalline salt, very soluble in absolute alcohol. Addition of platinum dichloride to the alcoholic solution precipitated a yellow substance, which was found to be the chloroplatinate of methylamine. Anderson repeated the same experiments with narcotine, morphine, and strychnine, with similar results. In the case of piperidine, the vapors released had an odor resembling that of bitter almonds and containing an amine that differed from valeramide by H2. Nicotine treated with dilute nitric acid, and brought to almost boiling, did not release nitrous vapors, but the distilled fluid was found to contain large amounts of HCN. Decomposition of the platinum salts In a paper published in 1857, Anderson wrote that it was well known that the platinum salts of the organic bases decomposed when boiled with an excess of platinum chloride. In the case of narcotine, the only alkaloid examined, the results was a true oxidation, yielding results similar to those obtained when treating the base with manganese dioxide or nitric acid. In this new work, Anderson found that the pure platinum salts underwent an entirely different decomposition, the results of which depended on the stability of the base. Anderson directed his attention to pyridine and picoline, which were known for their remarkable stability and resistance to oxidants. He reported that boiling an aqueous of the platinum salt of pyridine for several hours led to the precipitation of a fine sulfur yellow crystalline powder. This powder was found to be insoluble in water and acids and Revista CENIC Ciencias Químicas, Vol. 45, pp. 148-159, 2014. 156 to be decomposed by cold or boiling KOH, with evolution of pyridine. Analysis indicated that the powder was the salt of a platinum base, analogous to platinamine, and which he named platinopyridine, C10H3PtN. Anderson then described the reactions of platinopyridine, platinopicoline, platinochloride of ethyl pyridine, and the platinum salts of ethylamine, aniline, narcotine, and brucine. His results indicated that the platinum bases still contained replaceable hydrogen, proving that they were not nitrile bases. Alkaloids Anderson carried on fundamental research on the composition and properties of several alkaloids. On April 1850, he read the first one to the Royal Society of Edinburgh, discussing the composition of codeine, its reactions, and the products of its decomposition. Codeine had been analyzed by Pierre Jean Robiquet (1780-1840), its discoverer, and by several other chemists. The elemental analysis and formula they had reported for anhydrous codeine varied substantially: carbon content between 70.363 to 73.27wt%, hydrogen 7.12-7.585 %, nitrogen 4.82 % 5.353 %, and oxygen 14.61 % 16.699 %. Charles-Frédéric Gerhardt (1816-1856) had reported that crystallized codeine contained 67.77% to 67.87% carbon and 7.33 to 7.59% hydrogen. These variations led Anderson to repeat the analysis with all possible care. Anderson prepared codeine, as usual, from the mother-liquor from which morphine had been precipitated by ammonia. This liquid was evaporated to crystallization and the crystals pressed to separate the ammonium chloride, which was more soluble than the codeine hydrochloride. These operations were repeated until the greater part of the ammonium chloride had been removed and the crystals left were pure codeine hydrochloride. The crystals were then dissolved in boiling water, and the solution treated with concentrated KOH, whereby the codeine was partly precipitated as oil, which on cooling partly deposited in crystals. Another crop of crystals was obtained by evaporating the solution, and finally, when the mother liquor, had concentrated to a small bulk and cooled, it became filled with long silky needles of morphine, which had been retained in solution by the excess of KOH. The crystals of codeine were always found to be somewhat colored. They were purified by solution in HCl, boiling with animal charcoal, and reprecipitation by KOH. The resulting precipitate was finally dissolved in ether saturated with water to separate any remaining morphine. Anhydrous ether was not used because it dissolved codeine much less easily, and the solution when evaporated yielded small crystals of anhydrous codeine. Codeine, crystallized from water or water saturated ether, formed right prismatic crystals, containing two equivalents of water, which were given off at 100 C. An elemental analysis of several samples of the purified crystalline codeine indicated that it contained between 71.91% -72.09 % carbon, 7.04-7.14 % hydrogen, 4.41-4.60 % nitrogen, and 16.27-16.63 % oxygen, corresponding to the formula C36H21NO6, identical to the one reported by Gerhardt. Anderson described his codeine as an extremely powerful base, rapidly restoring the blue color of reddened litmus, and precipitating the oxides of lead, copper, iron, cobalt, nickel, and other metals from their solutions. It was precipitated by KOH from its salts, and insoluble in high concentrated KOH. It was soluble in ammonia, but not more so than in water. Codeine was slowly precipitated from all its solutions by ammonia, in small transparent crystals. Anderson went on to describe the preparation, analysis, and formula of a large number of codeine salts, among them codeine hydrochloride, hydroiodide, sulfate, nitrate, phosphate, oxalate, thiocyanate, as well as its double chloride with platinum. The following section of the paper described the reactions of codeine with sulfuric acid, nitric acid, bromine, chlorine, cyanogen, alkalis, and well as the description of the different products of the same (27 in total). For example, when codeine was dissolved in moderately strong sulfuric acid and the mixture digested for a while on the sand-bath, the fluid gradually acquired a dark color and after same time gave a precipitate with sodium carbonate. This precipitate was found to be amorphous codeine in a state of high purity. The precipitate was filtered, washed with water, dissolved in alcohol, and precipitated from the solution by water. It then formed a grey powder, fusing at 100 C to a black resinous mass; it was insoluble in water, readily soluble in alcohol, and precipitated by ether from the alcoholic solution. It was readily soluble in acids, forming amorphous salts. Heating a solution of codeine in concentrated nitric acid produced a violent reaction; nitrous fumes were abundantly released, and the solution acquired a red color. Evaporation of the fluid left a yellow resinous acid soluble, with a red color, in ammonia and KOH. Dilute nitric acid led to the formation of nitrocodeine, which crystallized from alcohol as slender silky needles. Nitrocodeine was sparingly soluble in boiling water, abundantly soluble in boiling alcohol, but sparingly in ether. It was soluble in acids, forming salts, which were neutral to test paper, and yielded the base in the form of a crystalline powder on the addition of potash or ammonia. Anderson described the preparation of nitrocodeine hydrochloride, sulfate, oxalate, and platinochloride. In the following two publications Anderson reported the results of his investigations on the crystalline components of opium. In spite of the many papers that had appeared regarding this alkaloid, the information available on the properties and composition of the various bases and indifferent constituents was far from being enough. Thirteen substances had already been identified, one acid and ten either basic or indifferent, all presenting different properties and crystalline form; among them were morphine, codeine, papaverine, narcotine, porphoroxine, opianine (identical with narcotine), thebaine, pseudomorphine, narceine, meconine, methylnarconine, and propylnarcotine. Their Revista CENIC Ciencias Químicas, Vol. 45, pp. 148-159, 2014. 157 reported formulae were far from being satisfactory, many of them were empirical, and others had been calculated using the older values of the atomic masses. In the first publication, Anderson reported the results of his experiments about narceine, and thebaine. These two alkaloids were prepared from the mother liquor of the preparation of morphine chloride by the method of Montgomery Robertson and William Gregory (1803-1858). This black tarry fluid was diluted with water, filtered, and treated with ammonia until precipitation stopped. The dark granular precipitate was rapidly removed, broken up with a small quantity of water, and repeatedly expressed. This precipitate contained narcotine, a considerable quantity of resin, and a small quantity of thebaine. The mother fluid contained narceine, and was stored for its preparation. Narcotine was separated and purified by boiling the precipitate with concentrated alcohol; the solution was filtered hot and left to cool. The precipitate of impure narcotine was washed with a strong solution of KOH, then with water, and finally crystallized several time from boiling alcohol. The thebaine contained in the original precipitate was treated with hot dilute acetic acid, which dissolved the bases and a small quantity of resin. The solution was treated with lead subacetate, which resulted in the precipitation of all the narcotine and resin, while the thebaine remained in solution. The filtrated liquid was treated with sulfuric acid to eliminate the excess of lead, filtered again, and the thebaine precipitated by ammonia. The impure thebaine was dissolved in boiling alcohol, and treated with animal charcoal, and on cooling the fluid became filled with shining plates, which were purified by several crystallizations. A similar process was used to separate narceine from the mother-liquor of the original ammonia precipitate. Anderson carried on the analysis of narceine from a quantity that had been purified by repeated solution both in water and alcohol, and which was absolutely white. He dried it at 110 C because at lower temperatures it lost its water with difficulty. His results indicated that narceine contained between 59.03 % 59.64 % carbon, 6.38 % 6.45 % hydrogen, 3.10 % 3.30 % nitrogen, and 30.88 % 31.22 % oxygen, corresponding to the formula C46H29NO18 and atomic mass 464.8. He reported that his narceine crystallized as extremely white needles, with a brilliant silky luster. It was slightly soluble in cold water, readily soluble in hot water, still more soluble in alcohol, and insoluble in ether. It was soluble in ammonia, in a diluted solution of KOH, and in diluted sulfuric, nitric, and hydrochloric acids. It reacted violently with cold concentrated nitric acid, with abundant release of nitrous vapors; after boiling for some time and dilution with water it gave a white precipitate, soluble in ammonia. The remaining solution was found to contain oxalic acid. Anderson also reported the preparation and properties of narceine hydrochloride, sulfate, nitrate, and its double chloride with platinum. The next section reported the analysis of thebaine, which had been purified by repeated crystallization, as 73.01 % 73.14 % carbon, 6.98 % 7.10 % hydrogen, 4.39 % 4.47 % nitrogen, and 15.41 % oxygen, corresponding to the formula C38H21NO6. Anderson reported that his thebaine crystallized from alcoholic or ethereal solution as brilliant square plates with a silver luster. It was insoluble in water and very soluble in alcohol and ether. It dissolved readily in acids forming salts, and was insoluble in ammonia and KOH. It reacted with strong sulfuric acid producing a deep red solution. It reacted violently with nitric acid with copious evolution of nitrous fumes, forming a yellow solution. Anderson reported the preparation and properties of thebaine hydrochloride and its double chloride with platinum. Anderson did not analyze narcotine because the composition reported by others was quite satisfactory. He studied its reaction with nitric acid and reported the formation of a new nitrile of opianic acid, which he named teropiamon, having the formula C60H29NO26. He indicated that the mother liquor of this new nitrile was found to contain cotarnine (C12H15NO4), hemipinic acid (C20H10O12), and two other new compounds, which he named opianyl and opianyl hydrate, having the formulas C20H10O10 and C20H10O8+H2O, respectively. Anderson summarized this paper saying that it contained the examination of 20 different compounds. In the following paper, Anderson reported that from the original mother liquor he had used to prepare narcotine and thebaine, he had been able to separate a substantial amount of papaverine and of meconine. He had separated and purified these two compounds and carried on experiments to determine their composition and properties, as well as the products of their reactions with a series of reagents. Papaverine was found to contain between 70.58 % 70.71 % carbon, 6.29 % 6.46 % hydrogen, 3.96 % 4.40 % nitrogen, and 18.60 % 18.96 % oxygen. Anderson reported the results of its reaction with nitric acid, bromine, chlorine, iodine, and calcium carbonate, and the composition and properties of the pertinent derivatives: nitropapaverine, its nitrate, hydrochloride, sulfate, and double chloride with platinum; bromopapaverine, its hydrobromide and hydrochloride; papaverine teriodide and pentaiodide; and that it was decomposed by sodium carbonate into ethyl and propylamine. Meconine was found to contain between 61.40 % 61.50 % carbon, 5.12 % 5.13 % hydrogen, and 33.37 % 33.48 % oxygen; this composition, as well as the properties, showed that meconine was identical with the opianyl Anderson had described in his previous publication. Anderson reported the results of the reaction of meconine with nitric acid, chlorine, bromine, iodine chloride, and a mixture of lead dioxide and sulfuric acid, and the composition and properties of the pertinent derivatives: nitropianyl, chloropianyl, bromopianyl, and iodopianyl. In 1862, Anderson delivered a discourse to the Fellows of the Chemical Society summarizing the history of the chemistry of opium and the work he had realized on the subject. Revista CENIC Ciencias Químicas, Vol. 45, pp. 148-159, 2014. 158BIBLIOGRAPHIC REFERENCES 1. Mills, E J. The Late Dr. Thomas Anderson. J. Chem Soc. 1875; 28: 1309-13132. Anderson T. B. The Forgotten Chemist? Chem Britain. 1992; 28: 442-444,3. Rodwell G F, Anderson Thomas (1819–1874), rev. T.B. Anderson; in Oxford Dictionary of NationalBiography, UK: Oxford University Press; 2004.4. Anderson T. Analysis of New Mineral Species. New Phil J Edin. 1842; 32: 147-152.5. Anderson T. Analysis of Caporcianite and Phakolite, two New Minerals of the Zeolite Family. New Phil JEdin. 1843; 34: 21-24.6. Anderson T. Sur le Poids Atomique de l’Azote. Ann Chim Phys. 1843; [3] 9: 254.7. Anderson T. Elements of Agricultural Chemistry. Edinburgh; Adam and Charles Black :1860.8. Anderson T. On the Colouring Matter of Morinda Citrifolia. Trans Roy Soc Edin. 16: 1849;435-443.9. Anderson T. On the Colouring Matter of the Rottlera Tinctoria New Phil J Edin. 1855;1:296-302.10. Anderson T. On Certain Products of Decomposition of the Fixed Oils in Contact with Sulfur. Phil Mag.1847; [3] 31, 161-172.11. Zeise W. C. Om Nogle Nye Svovel-Foreninger. Skand Naturf Förhandl. 3:1842;303-314.12. Runge F. Über Einige Produkte der Steinkohlendestillation (On some Products of Coal Distillation). AnnPhys 31: 1834; 65-77, 513-524; 32, 308-332.13. Anderson T. On the Constitution of Picoline, a New Organic Base from Coal Tar. New Phil J Edin. 1846;41:146-156, 291-360.14. Unverdorben O. Über die Eigenschaften des Odorin, Animns, Olanins, und Ammolins. Poggend. Annal.1827;11: 59-74.15. Anderson T. On the Products of the Destructive Distillation of Animal Substances Part I. Phil Mag. 1848;[3] 33: 174-186.16. Anderson T. On the Products of the Destructive Distillation of Animal Substances. Part II. Phil Mag. 1851;[4] 2 : 457-471,17. Anderson T. On the Products of the Destructive Distillation of Animal Substances. Part III. Phil Mag 1855;[4] 9 : 145-150, 214-225.18. Anderson T B. Williams G. On Some of the Basic Constituents of Coal-Naphtha. Brit Assoc Rep. 1855; 74.19. Dumas J B. Recherches sur les Combinaisons de l’Hydrogène et du Carbone. Ann Chim Phys. 1832; [2],50: 182-197.20. Laurent A. 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Sur la Constitution et sur les Produits de Décomposition de la Codéine. Ann Chim Phys 1852;[3] 34: 493-501.29. Anderson T. Researches on Some of the Crystalline Constituents of Opium, Edinburgh: Neill and Co; 1852.30. Anderson T. On the Constitution of Codeine and its Products of Decomposition. Proc Ro. Soc Edin. 1853;20: 57-86.31. Anderson T. Researches on some of the Crystalline Constituents of Opium. Trans Roy Soc Edin. 1853; 20: 347-375.32. Anderson T. Researches on some of the Crystalline Constituents of Opium. Trans Roy Soc Edin. 1853; 21:195-218.33. Anderson T. On the Chemistry of Opium, Quart. J Chem Soc. 1862; 15: 446-455. 34. Anderson T. Note on the Use of Subacetate of Lead as a means of Separating some of the VegetableAlkaloids. Proc Roy Soc Edin. 1862; 4: 92-92.35. Robiquet P J. Nouvelles Observations sur les Principaux Produits de l’Opium. Ann Chim Phys. 1832; [2]