May, 1925
I N D U S T R I A L A N D ENGINEERING CHEMISTRY
47 1
Pyrrole from New Sources-Some Uses’ By Joseph Michelman 20
SEAVRR
ST., ROXBCRY, MASS.
are too costly for this purpose. However, “glue stock,” from leather scrap2 led to the conclusion that leather which constantly accumulates in considerable quantities in and gelatin decompose upon destructive distillation abattoirs and tanneries and from which glue is manufacinto substances common to both. The products obtained by tured, is more suitable industrially and economically. The composition of the glue stock for this process is conWeidel and Ciamician3 upon destructively distilling gelatin were in accord with those obtained by the writer upon sub- fined to hides, hide trimmings, fleshings, skivings, shavings, jecting leather scrap to the same treatment, excluding, etc., and to similar matter, including scrap leather, that has is, from which the tanning subobviously, those substances arising from the tanning matter. been “detanned”-that The most characteristic of these decomposition products stances have been removed. As has been shown, it is deare pyrocoll and the pyrroles: the absence of pyridine bases sirable to have these raw materials in a state of purity a p proximating gelatin or-glie, and‘iatty acid nitiiles ‘ and if they are not already is equally noteworthy. It in this condition, they may is now possible to make a Extension of the results obtained from the destructive be subjected to a liming further generalization that distillation of leather scrap and of gelatin has suggested process as is ordinarily used pyrrole and pyrrole derivaglue stock as another source for the industrial preparain dehairing and defleshing tives, especially pyrocoll, tion of the pyrroles and pyrocoll. From a chemical hides. By the action of the are the characteristic disstandpoint, prepared glue stock is satisfactory. Howlime solution the epidermd t i l l a t i o n products arising ever, an abundance of cheap raw materials in an excellayers are loosened and the from animal matter comlent condition characterizes leather scrap and makes it fatty matter is saponified. posed of internal and expreeminently suitable for this purpose. The substances that would ternal gelatinous and memA few uses for the pyrroles are suggested. The reducgive rise to the formation branous substances and contion into pyrrolidine derivatives, which might be used of pyridine bases and fatty nective tissue, a necessary as substitutes for nicotine as an agricultural poison, is acid nitriles are thereby to criterion for such animal pointed out. Readily accessible pyrrole offers oppora large extent removed. matter being that it should tunities for the synthesis of some of the alkaloids of the (Weidel and Ciamiciand be capable of passing into a pyrrolidine series and of compounds of pronounced postulated that the presence gelatinous or glutinous conphysiological activity. of the pyridine bases in dition upon boiling with bone oil was due to the water. condensation of the acroThe foregoing generalization may havesome biochemical significance, but only its lein from the fats with ammonia and aliphatic amines.) industrial applications will be considered a t this time. I n The alkali need not be removed from the stock, which is this connection, it suggests another source, in addition to dried and destructively distilled similarly to scrap leather. scrap leather, for obtaining pyrocoll and the pyrroles on an Since glue stock and leather scrap yield in the main the same distillation products, excluding those substances industrial scale. arising from the added tanning matter, the methods of reRaw Materials covery of the products from glue stock are the same as those outlined for leather scrap. As is well known, animal offal of various descriptions has been subjected to destructive distillation, frequently for costs the recovery of ammonia and animal charcoal, and some- . The condition, the cheapness, and the present plentiful times merely for its disposal. This practice of using raw materials from the varied and indiscriminate sources results supply of leather scrap give it outstanding advantages over in a mixture of distillation products of such complexity that glue stock as an industrial source for the pyrroles. Leather isolation and purification of its constituents become im- scrap is $5 to $10 a ton a t the present time, has a moisture practical. Even bones, which can supposedly be selected content of only 6 to 15 per cent, and requires little if any with more care than the average animal offal, give a dis- preparatory treatment, as has been shown in the preceding tillate, “bone oil,” containing, among many other sub- paper.2 Glue stock is variously quoted-for instance, hide stances, pyridine bases, fatty acid nitriles, and the pyrroles. trimmings are about $20 a ton-but as such materials have Some of these are not sufficiently valuable, and others com- an exceedingly variable content of glue-yielding substance plicate the extraction and recovery of the more valuable and a large amount of moisture, and may require preparatory constituents. The presence of these associated impurities treatment, the cost per ton mounts considerably higher. can be avoided by selecting raw materials closely related to Yields gelatin, which has been shown by Weidel and Ciamician4 The yield of the pyrroles and pyrocoll varies with the to yield principally the pyrroles and pyrocoll uncontamamount of animal matter present in the raw materials, and inated by pyridine bases or fatty acid nitriles. The chemical distinction between gelatin and glue is merely one of purity, is larger from chrome-tanned than from vegetable-tanned and they would yield the same distillation products, but both leathers. The hide substance contents of these leathers are 50 to 75 per cent and 35 to 50 per cent, respectively. Thus, 1 Received November 25, 1924. glue stock for this process is to be evaluated upon its content ’THIS JOURNAL, 17, 247 (1925). of gelatinous matter, which is generally lower than that in 8 Monalsh., 1, 279 (1880). leather. The pyrocoll, which is readily separated from the 4 Bcr., 18, 85 (1880).
A
S IXVESTIGATION of the decomposition products
INDUSTRIAL A N D ENGINEERING CHEMISTRY
472
other distillation products and purified, can be used with reasonable accuracy as indicative of the yields of the pyrroles as well. It was thus observed that the yield of pyrocoll decreases with more compact baling of the scrap-that is, with an increase in the all-over density of the raw materials in the bales or billets. On the other hand, more compact baling results in a char of greater density, which is very desirable. The industrial value of the products will determine the method of operation, which is controllable over a wide range. The utilization of other waste products composed of leather, such as discarded footwear, leather board, old belting, etc., is also possible but not economically feasible at present. Pyrrole in Synthetic Chemistry Scrap leather and glue stock are thus fruitful sources of pyrrole and its derivatives, which offer numerous possibilities for synthesis. A few of these applications will be discussed very briefly. HYDROGENATION-The hydrogenation of pyrrole and its homologs yields exceedingly interesting products possessing pronounced alkaloidal character. The relationship of pyrrole through pyrrolidine to nicotine is apparent from their formulas : HC-CH
I1
HC
ll
HC-CH
I
HzC-CHz
1
CH HzC
I
CHs HaC
HzC-CHt
t
I
CH2 HzC
\”
“/
H
H
‘Hd
Pyrrole
Pyrroline
Pyrrolidine
CH--
\N/’
\/
Me Nicotine
This relationship of chemical constitution is also manifest in their similarity of pharmacological behavior. Tunnicl8e and Rosenheim5 have investigated the physiological action of the reduced pyrroles and noted the close relationship in this respect between pyrrolidine and nicotine. This suggests a very important use for the reduced pyrroles as an agricultural poison as a substitute for nicotine sulfate. For this purpose the reduced homologs of pyrrole should be very efficacious, because, as Tunnicliffe and Rosenheim have pointed out, the pharmacological effects of the pyrrolidine ring are greatly intensified by the introduction of a side group-for instance, the inactive pyridine ring. The hydrogenation of the pyrroles may proceed in two stages: Reduction to Pyrroline-The electrolytic reduction of the pyrroles to the corresponding pyrrolines as proposed by Dennstedte gives yields claimed to be almost quantitative. Knorr and &be,? using metals and mineral acids, obtained pyrrolines and some members of the pyrrolidine series, however, with yields less than one-half. Reduction to Pyrrolidine-Padoas obtained pyrrolidine by ppssing pyrrole vapor and hydrogen through a tube containing reduced nickel, with a yield of 25 per cent. Putoching recently repeated this work and analyzed the byproducts of the reaction. Willst&tterloattempted to hydrogenate pyrrole derivatives in ether solution with platinum black and hydrogen, but without success; pyrroline derivatives could be reduced, however. Pure pyrrole in acetic acid can be reduced to pyrrolidine by this method with a yield of about 80 per cent. Kurt Hess” has accomplished the quantitative reduction of pyrrole to pyrrolidine by Zcnfr. Physiol., 16, 93 (1902); Chcm. Zcnfr., 73 (111, 390 (1902). German Patent 127,088 (1902); Chcm. Zcnfr., 73 (I), 338 (1902). 7 Ibid., 7 1 (I), 71 (1901).
5
6
8Gaze. chim. i f a l . , 86 (II), 317 (1906). 0 Ber., SS, 2742 (1922). 10
Ibid., 4S, 1477 (1912): Ann., 386, 207 (1911).
‘1
Bw., 46, 3120, 4104 (1913).
catalytic hydrogenation with platinum black out of contact with the air. HALOGENATION-CiamiCian and Silber12 prepared tetraiodopyrrole, or iodol, by the action of iodine on pyrrole in the presence of alkali. There are several other methods.13 Iodol is said to possess the same physiological properties as iodoform, but it differs from the latter in being odorless and nonpoisonous. The action of sulfuryl chloride on pyrrole yields a series of progressively chlorinated products. PoLYMERIzATIoN-The polymeric change of the pyrroles into the corresponding indoles was discussed in the preceding paper.* To this may be added that Plancher and Ciusa14 effected the conversion by using zinc acetate and acetic acid. The use of indole as a perfume base in synthetic civet, jasmine, and neroli oils is well known.16 The indoles have been proposed frequently as various dye intermediates, but little if any development has occurred in this direction, probably because of their prohibitive cost, which is $6 per ounce for indole a t present.l6 SYNTHESIS OF ALKALOIDS-The presence of a pyrrolidine group in the alkaloids, cocaine, atropine, tropine, tropacocaine, homatropine, etc., is well recognized. The preparation of pyrroles substituted by derivatives of propane presents the possibility of synthesizing some of the alkaloids of the pyrrolidine group, which is reflected in Kurt Hess”’ synthesis of the alkaloid hygrine and in a series of patents of Bayer & Company. Compound AI8 may be prepared from pyrrole and a-propylene oxide through the Grignard reagent. The compound A is readily reduced with good yields to the compound B.I9 After the imide hydrogen atom of B is replaced by a methyl group through the action of formaldehyde, the compound C results.20
(‘ N
I
Vol. 17, No. 5
HC=C-CH*
11
AH CHOH--+
1
HC-CH
’
CH,
CH
CH-CH:
1
NH
I
l
1
CHs-CH,
I
CHOH-
l
CHI
CHr4!H-CH*
I 1 I
l l
l
NMeCHOH
CHI-CHI
l
CH,
A B C The similarity of the structure of compound C to that of tropine is noteworthy. Compounds of the type A , B, and C are intended as “intermediates in the preparation of pharmaceutical products.” Nole-Since this paper was written, the writer has received a private communication stating that.the synthesis of tropine from pyrrole has actually been carried out. Accordinely, the syntheses of tropacocaine, and possibly homatropine, are in sight.
A voluminous literature has accumulated upon the chemistry of pyrrole and its derivatives, which has been well summarized by Ciamiciaq2* J. Schmidt,22 and MeyerBer., 18, 1766 (1885). German Patents 35,130 and 38,423 (18S6). 14 A f f r accad. Lrnrci, l S , 447 (1906). 1) German Patent 139,822 (1903). 1 8 Drug. Chem. Markcls, October 15, 1924. 17 Em., 46, 3113, 4104 (1913). 18 Chcm. Zcnfr., 86 (II), 1136 (1914). 1) Ibid., 86 (I), 583, 926 (1915). 20 Ibid., 86 (II), 1033 (19151, 88 (IU, 146 (1917). 21 Bcr., 37, 4200 (1904). 11
18
22 9)
“Die Chemie des Pyrroles,” Stuttgart, 1904. “Organische Chemie,” Vol. 11, 1920, p. 146.
Du Pont Organizes Viscoloid Company-Plans have been completed for the formation of the du Pont Viscoloid Company to manufacture and deal in pyroxylin plastic articles. The company will take over the business heretofore conducted by the Viscoloid Company, Inc., with plant at Leominster, Mass., and the pyralin business formerly conducted by the du Pont Company with plants at Arlington, N. J., Poughkeepsie, N. Y., and Norwich, Conn. The main office will be in New York. B. F. Davis, general manager of the du Pont company’s pyralin department, will be president of the new organization.
