IXDUSTRIAL AND ENGINEERING CHEMISTRl
360
mental tube. For the calculation of the weight of the sample a value of the density of liquid butane of 35.795 pounds per cubic foot a t 77.0" F. was taken. The results are given in Table I and shown graphically in Figure 2. The following table compares the results with data of other investigations: -Dana et RZ. (5)Liquid Vapor
Temp. F. 70 100 130 160 190 220 250
36.06 34.84 33.49
0.347 0.552 0.826
... ...
... ...
...
...
...
...
-Sage et RZ. (6)Liquid Vapor Pounds per cubic foot 36.31 36.01 33.75 32.36 30.66 28.77 26.34
-Kay-Liquid
0.344 0.556 0.861 1.291 1.896 2.77 4.14
36.07 34.86 33.57 32.13 30.57 28.72 26.42
Vapor
., O:k6 1.27
1.83 2.69 3.94
Critical Constants The critical temperature and pressure were found to be 306.0' F. and 550.1 pounds per square inch, respectively. By extrapolation of the mean density line to the critical temperature (Figure 2), a value of 14.24 pounds per cubic foot was obtained for the critical density. The following table shows a comparison with values of the critical constants obtained by others: Investigator Beattie et al. (1) Seibert and Burrell ( G ) Kay
Pressure Lb./sq, in. 550.7 529.0 550.1
Temp. F. 305.62 307.4 306.0
Density
Lb./cu. j t . 14.05 ,..
14 24
VOL. 32, NO. 3
Compressibility of n-Butane in Liquid and Vapor State Fifteen isotherms in both the high- and low-pressure regions, covering the temperature range from 100" bo 536' F., were obtained for n-butane. The data were plotted and values of the pressure and temperature were read from the curves for regular intervals of the volume. These pressure-temperature data ;:ere then plotted to give the isochlors or curves of constant volume from which the values of the pressure, TTolume, and temperature given in Tables I1 and I11 were obtained. The uncertainties in the tabulated values are estimated not to exceed the following amounts: 0.4 per cent in the pressure, 0.15 per cent in the volume, and 0.1" F. in the temperature. These data are in excellent agreement Kith the data of Beattie, Simard, and Su ( 2 ) .
Literature Cited (1) Beattie, Simard, and Su, J . Am. Chem. Soc.. 61,24 (1939). (2) Zbid., 61,26 (1939). (3) Dana, Jenkins, Burdick, and Timm, Refrig. Eng., 12, 387 (1926). (4) Kay, IND. Eso. CHEM.,32, 383 (1940). (5) Sage, Webster, and Lacey, Ibid., 29, 1188 (1937). (6) Seibert and Burrell, J . $m. Chem. SOC.,37, 2683 (1915). PRESENTED (in combination with the paper on page 353) before the Division oi Petroleum Chemistry a t the 97th Meeting of the American Chemical Soriety, Baltimore, Md.
Germicidal Mercury Derivatives of Pyridine J
M. W. SWANEY,lM. J. SKEETERS,2 AND R. NORRIS SHREVE Purdue University, Lafayette, Ind.
.M
ANY inorganic compounds of mercury, typified by
corrosive sublimate, are relatively strong germicides. Because of their high tissue toxicity and lethal properties, however, they are not particularly desirable for general disinfection. The trend during recent years has been toward organic mercurials, particularly of the aromatic series, many of which combine high germicidal activity with relatively low toxicity. Mercuration in the benzene series has been known and studied for many years ( 5 ) . It proceeds with ease, and the products are generally obtained in good yields. During the past two decades a multiplicity of organic mercurials of the type R-Hg-X have been tested germicidally. A few have attained considerable importance and are used at, the present time in the medical profession under the names Merthiolate, Metaphen, Merphenyl, Xercurophen, and Mercurochrome. Mercuration of the pyridine ring, on the other hand, has presented considerable difficulty. Prior to the beginning of this work only one simple pyridylmercuric compound of the type X-Hg-CsRJ (in which mercury is attached to car1 2
Preaent address, Standard Oil Development Company, Elizabeth, N. J. Present address, National Aniline & Chemical Corporation, Buffalo, E.Y .
lion) had been reported. 1lcClelland and Wilson (1) prepared and isolated one pyridylmercuric compound by reacting mercuric acetate and pyridine a t elevated temperatures under anhydrous conditions. Presumably the sole purpose of their work was to show that two alleged pyridylmercuric compounds reported earlier by Xachs and Eberhartinger (2) were, in fact, nitrogen-addition compounds of pyridine. S o n e of these materials was tested bacteriologically. The reaction of pyridine and anhydrous mercuric acetate at 180" C. is complex. From the nature of the pyridine ring, three monomercury substitution products, six dimercury derivatives, etc., are possible. il'hen pyridine is reacted with mercuric acetate a t this temperature for 2 hours, %-everylow yields ( 5 to 10 per cent) of monosubstitution products are obtained, the major portion of the reactants being transformed into insoluble polymercurated pyridines of questionable value. In the present ~ ~ o itr is k shown that the mercuration of pyridine is greatly influenced by the presence of water, and that polymercuration can be minimized by arresting the reaction a t the point of incipient sludging. In this nay, up t o about 50 per cent yields of pyridylmercuric compounds of high germicidal potency have been obtained The writers prepared a number of pyridylmercuric derivatives, along with several phenylmercuric compounds, and compared their germicidal activities with the more widely known mercurials of present-day use; all were tested against Staphylococcus aureus and BacillzLs coli organisms under identical conditions.
MARCH, 1940
INDUSTRIAL AND ENGINEERIKG CHEMISTRY
361
&Iercuration The reaction between pyridine and mercuric acetate at elevated temperatures was investigated over a rather wide range of conditions. The mercuration of pyridine was effected at 155" C. to give yields of monosubstitution products which make the process coinniercially feasible. The presence of substantial quantities of water minimizes the production of polymercurated derivatives. For the first time a true pyridylmercuric compound has been tested germicidally. This is an extremely potent type of bactericidal agent of relatively low host toxicity. 3-Pyridylmercuric chloride in a dilution of 1 part in 2 million parts of water completely prevents the growth of Staphylococcus aureus. The mercury derivatives of pyridine are stable toward hydrolysis, and possess possible application as antibacterial agents in medicine and many commercial processes.
Phenylmercuric derivatives are readily prepared by several methods: ( a ) action of mercuric acetate on benzene, (b) reaction of mercuric halide n-ith bromobenzene in the presence of sodium or the action of sodiuni amalgam on bromobenzene, and (c) decompositioii of phenylmagnesium halide with mercuric halide. The latter of these methods deserves a few words of explanation. I t has been reported (4)that phenylmercuric chloride results from the action of mercuric chloride on phenylmagnesium bromide. The writers obtained phenylmercuric bromide instead in a high yield by the following reaction: --Ptlg--Br
+ Hac12 +
-Hg-Br $-
MgCL
I n order further to substantiate this, lithium phenyl Tas prepared by the action of lithium metal on bromobenzene in ether solution (nitrogen atmosphere). When mercuric chloride was added t o the resulting mixture of lithium phenyl and lithium bromide, phenylmercuric bromide was obtained as the final product. Of the above methods of mercuration, only the first has proved successful with pyridine. I n this investigation mercurations were carried out in glass bombs so that the reaction< could be followed visually. When mercuric acetate is added to pyridine a t room temperature, a nitrogen-addition product forms initially which is soluble in excess pyridine. On being heated to a sufficiently elevated temperature, this addition product rearranges anti true mercuration occurs. In the case of pyridine the main tendency is for mercuratioii to take place on the 3- or beta-carhon, as follows:
matelj- that of molar equivalence. Since a n excess of pyridiiie Wac used as solvent for the reactants (the excess was recovered and re-used). the runs summarized in Table I11 represent the yarious maxima of the curves obtained at the various temperatures when employing 8 moles each of pyridine and water and 1 mole of mercuric acetate. Yields are calculated on the 0 0 back of the mercuric acetate added. I ! I/ C"L-0 Hg-O-CCHz The recommended procedure for 0 \pq/ the -preuarat'ion of i-ovridvlmer/ x\, I! 180' C'.+ ' 1 C) CH,COOH curic acetate is as follows: Nercuric + (CH,C-O--)*Hg-+ I, acetate (1 mole) is dissolved in ' Hg-OC-CHB pyridine (8 moles) and water (8 moles) is added. The charge is heated under pressure in glass or glass-lined apparatus for 2.5 It was observed that, as the time of reaction betneen pyridine hours a t 1%' C. The reaction product is filtered from any and mercuric acetate - m s alloned to increase, the yield of in~olublematter, and the volatile materials are removed by inonopyridylmercuric compound also increased to a maximum value, after which the yield fell off rapidly. This maximuni in the time-yield curve was accompanied by the first appearance of insoluble polymercurated compounds. As polymerTABLEI. h1ERCURATION O F PYRIDISE WITH kYHYDROUS h l E R curation was allowed to proceed, the monosubstitution prodCERIC ACETATEAT 180" C. ucts were rapidly used up and removed from the reaction Reaction time, min. 16 30" 60 105 120 medium as insoluble materials. In other words. the point of Yield of monomeroury compound, yo 11.0 18.2 1 4 . 2 9.0 8.6 maximum yield coincided with incipient sludging. Runs Initial appearance of insoluble residue. made at 180" C. are summarized in Table I. Although 180" C. had been employed by ?\lcClelland and Wilson ( 1 ) as the mercuration temperature of pyridine, TABLE11. TIME-TEMPERATTRE RELATION O F THE A~VHYDROES time-yield experiments were made a t a series of temperatures MERCUR.ITIONOF PYRIDINE n-ith the result that 160" C. proved to be more desirable for Temp., C . 155 160 170 180 Time of mas. 3-ield of monomercury oomthe anhydrous mercuration of pyridine than 180" C. This IS pound. min. ... 62 42 30 evident from the condensed data in Table 11. Max. yield of monomercuryoompound, % Xone 24.3 19.8 18.2 I n a study of the effect of other substances on the mercuration of pyridine, it was observed that the addition of water TABLE111. MERCURATION OF PYRIDINE WITH MERCURIC ACEto the reaction medium greatly favored the formation of deTATE IPIT PRESEXCE OF WATER sirable reaction products. Mercuration of pyridine in the Temp.. C. 140 145 150 155 160 165 170 presence of water not only produced higher yields of monoTime of max. yield of monomerouryderivative, min. 630 660 240 150 133 105 72 substitution products but allowed the reaction to proceed a t Max. yield of monomercury a somewhat lower temperature. I t was noted further that 30.2 33.4 33.9 49.2 3 3 . 4 33.5 33.5 compound, % the optimum proportion of water to pyridine was approyi-
P\
1
v
(
v
^ I
~
1 v-
0
Y
INDUSTRIAL AND ENGINEERING CHEMISTRY
362
VOL. 32, NO. 3
distillation, preferably under reduced pressure. The crude pyridylmercuric acetate remaining is recrystallized from hot benzene. The pure product, obtained as cottony white needles, melts a t 178" C. and is very soluble in water.
The pyridylmercuric compounds are remarkably stable toward hydrolysis. Twenty per cent sodium hydroxide, for example, does not convert pyridylmercuric acetate to the corresponding hydroxide. Seither are the pyridylmercuric compounds precipitated by proteins, a factor of greatest importance in disinfection work. This high stability suggests TABLE IV. RELATIVE POTENCIES OF MERCURIALS IN PREVENT- the germicidal utility of the pyridylmercuric compounds even ING GROWTH OF ORGANISMS FOR 48 HOCRS AT 37" C. in very dilute solutions over a wide pH range, Max. Effective Dilution, Parts Water per P a r t of Mercurial Compound
Phenylmercuric chloride hlerthiolate (o-CzHsHgS.CsH4.COONa) Mercurophen (p-hydroxymercuri-a-nitrophenol) Metaphen (acetoxymercurinitro-o-cresol) Mercuric chloride Mercurochrome (hydroxymercuridibromofluorescein)
Staph. a w e u s
B. coli
2,000,000 1,700,000 1,700,000 600,000 400,000
550,000 400,000 400,000
.... ....
4,000.000 3,000,000 2,000,000 1,000,000 900,000
350,000 300,000 500,000 150,000
200,000
100,000 250,000
50,000
50,000
aoo,ooo
500,000
The preparation of other pyridylmercuric salts may be made from the crude or purified acetate. For example, the crude mercuration product, after removal of excess pyridine, is-dissolved in water, sodium hydroxide added to precipitate unreacted mercuric acetate, and the solution filtered. The filtrate is returned to its original pH by addition of acetic acid, then sodium chloride solution is added to precipitate pyridylmercuric chloride. The chloride is purified by recrystallization from water in the form of white needles melting a t 280" C. I n Tables I, 11, and I11 the yields of monomercury derivative are based on 3-pyridylmercuric chloride recovered in this manner. 3-Pyridylmercuric nitrate was obtained by the addition of sodium nitrate to a solution of pyridylmercuric acetate and also by reacting pyridylmercuric chloride with silver nitrate. Identical products were obtained in both cases. It crystallized from water in the form of fine crystals, which by analysis were shown to be the normal nitrate and not the basic nitrate as is the case when silver nitrate is reacted with phenylmercuric chloride in the presence of water. Pyridylmercuric nitrate does not possess a definite melting point. However, it is characterized by possessing a peculiar explosive tendency a t elevated temperatures. When a capillary melting-point tube containing 3-pyridylmercuric nitrate is heated gradually from room temperature to 360" C., the nitrate darkens slowly but does not melt. However, when a freshly filled capillary of the nitrate is plunged into a bath previously heated to 360" C., the nitrate decomposes explosively. A series of such tests a t various temperatures showed that the critical point lies at 308-309" C. At any temperature above this point sudden immersion causes the nitrate to explode, whereas immersion a t any lower temperature causes the nitrate merely to darken without exploding. Throughout the work this critical explosive temperature was found t o be a reliable method of identifying 3-pyridylmercuric nitrate. a-Aminopyridine and a-picoline (methylpyridine) were more easily mercurated than was pyridine itself. a-Aminopyridine was mercurated a t 100" C. with hydrous mercuric acetate, followed by decomposition with sodium chloride, to give an 88 per cent yield of 2-amino-5-pyridylmercuric chloride, which crystallized in needles (melting point, 197.5' C.) from aqueous alcohol. a-Picoline was mercurated a t 150" C. to give a 61 per cent yield of a monomercury derivative believed to be the 2-methyl-5-pyridylmercuriccompound although its structure was not definitely established.
Identification of Products The pyridylmercuric compounds prepared were analyzed for mercury by the method of Tabern and Shelberg (3). Sitrogen analyses were by the Dumas method, and halogen determinations (Carius) were made on the pyridylmercuric chlorides. The position occupied by the mercury in the pyridylmercuric compounds was ascertained by decomposing the latter with bromine and potassium bromide, the resulting bromopyridine being identified as 3-bromopyridine by its physical properties and the melting point of its picrate. I n the case of a-aminopyridylmercuric chloride, decomposition with bromine and hydrogen bromide gave 2,5-dibromopyridine which was identified by its melting point.
Germicidal Evaluation All the mercurials tested, including the commercial preparations listed in Table IV, were tested simultaneously under identical conditions. They were tested in aqueous solution against standard strains of bacteria. I n bacteriostatic tests (growth prevention) 0.5-cc. quantities of aqueous solutions of the mercurials were admixed with 9.5-cc. portions of sterile agar-peptone-beef extract culture medium carefully adjusted to a pH of 6.5. The various mercurial-agar mixtures were then impregnated with 2-mm. loops of 24-hour cultures of Bacillus coli (300,000 to 500,000 organisms per loop) or Staphylococcus aureus (150,000 to 375,000 organisms per loop). The specimens thus treated were incubated in Petri dishes for 48 hours a t 37" C. after which they were examined for bacterial growth. The results, expressed in terms of the maximum dilution of mercurial which completely prevented growth of the organisms, are summarized in Table IV. A review of the literature reveals that different investigators may often report very different bacteriostatic values for the same substance. I n order to eliminate any such discrepancy arising from failure to duplicate experimental conditions, all the compounds reported in this article were tested simultaneously under precisely identical conditions and against the same cultures of the two strains of organisms. Therefore, the data in Table IV are comparable among themselves, although the germicidal potency of a particular substancefor example, phenylmercuric nitrate-may not agree precisely with similar values found elsewhere in the literature. TABLE v. LETHALDOSAGES O F ORGANOMERCURIC
Compound 3-Pyridylmercuric chloride 3-Pyridylmercuric nitrate 3-Pyridylmercuric acetate Phenylmercuric chloride Phenylmercuric nitrate (basic) Phenylmercuric acetate
Soly. in H10 a t 2 5 O C. Grams/liter 0.22 1.89 Very sol. 0.05 0.80 4.0 (approx.)
COMPOUNDS
Lethal Dosarce per Kg. ofBody Weight I
Rats
18.0
Mice Mo. 53.0 17.0 18.0
3i:5
I6:o
Mo. 53.5 17.0
24.0
..
Toxicity toward Rats and Mice Weed and Ecker (4) tested the animal toxicity of basic phenylmercuric nitrate and found it to be far less toxic than
MARCH, 1940
INDUSTRIAL AND ENGINEERING CHEMISTRY
mercuric chloride. I n the present investigation various quantities of the mercurials were fed orally to rats and mice which were then kept under observation for several weeks. By using a number of animals for each test and feeding different quantities to different ones, it was possible to determine the lethal dosages of the materials (Table V). It is evident that the pyridylmercuric compounds are of very low toxicity for mercurials.
Summary
363
industrial applications, such as antimolding agents in the paper and glue industries, and as disinfectants for plant seeds, cosmetics, soaps, etc.
Acknowledgment Acknowledgment is extended to P. A. Tetrault of Purdue University for cooperation with the bacteriological test,s, and to the Mallinckrodt Chemical Works for their support in this investigation.
Literature Cited
Mercuration of the pyridine ring is facilitated by the presence of water a t 155" C. The pyridylmercuric compounds obtained are strong germicides of relatively low host toxicity. Substituent groups, such as amino or methyl, increase the ease of mercuration but lower the germicidal activity of the resulting mercurials. On the whole, the pyridylmercuric compounds are slightly weaker germicides against Staphylococcus aweus than the corresponding phenylmercuric derivatives, although 3-pyridylmercuric chloride exhibited a stronger bacteriostatic activity against B. coli than any mercurial tested. The superior solubility of the pyridylmercuric compounds favors their possible use in medicine and for many
(1) McClelland, N. P., and Wilson,
It. H., J . Chem. SOC.(London), 1932. 1263. (2) Sachs, G., and Eberhartinger, R., Ber., 56, 2223 (1923). (3) Tabern, D. L.. and Shelberg, E. F., IND. ENG.CHEM.,Anal, Ed., 4, 401 (1932). (4) Weed, L. A,, and Ecker, E. E., J . Infectious Diseases, 49, 440 (1931). (5) Whitmore, F. C., "Organic Compounds of Mercury", A. C. S. Monograph, New York, Chemical Catalog Co., 1921. THE material contained i n this article represents one phase of a n investigation on germicidal compounds containing t h e pyridine nucleus and was extracted from the doctoral theses of M. W. Swaney and M. J. Skeeters, submitted t o Purdue University in partial fulfillment for the degree of doctor of philosophy.
COAL CARBONIZATION Gas Pressures within the Uncarbonized Part of a Charge D. A. REYNOLDS AND G. W. BIRGE Central Experiment Station, U. S. Bureau of Mines, Pittsburgh, Penna.
The manner in which gas pressures develop within the uncarbonized part of a charge of coal carbonized in cylindrical steel retorts is described. These pressures increase irregularly as the plastic coal layer moves to the middle of the retort and reach a maximum at the time the innermost coal attains the plastic state. For the coals investigated, maximum pressures vary according to the rank of the coal carbonized, increasing with decrease in the volatile content. The maximum gas pressure obtain-
vv
-HEX coal is heated to carbonization temperatures,
the first macroscopic change occurs between 370 O and 425" C. with most coals or blends which are usable in by-product ovens. In this temperature range if a large enough proportion of the coal constituents fuses, the coal becomes plastic and the so-called plastic state is formed. On further heating, this plastic coal undergoes physical and chemical changes until solidification occurs. The temperature range of plastic coal was shown to be between 45' and SO" C. for nine American coals or coal blends ( 2 ) . \%'hen coking coal is externally heated in ovens or retorts, a plastic coal layer forms adjacent to the heating walls and moves inward parallel to the source of heat. This layer separates the inner core of
able in carbonization of low-volatile coals is not greatly modified by the temperature of carbonization, provided the heating rate is rapid enough to ensure a continuous plastic layer. Maximum pressures developed on carbonizing medium- and low-volatile coals decrease as the temperature of carbonization is increased. These pressures may contribute to the expansion of the charge by opposing the escape of volatile matter from the plastic coal layer inward to the zone of uncarbonized coal.
uncarbonized coal from the outer solidified portion of the charge, which ranges from semicoke to true high-temperature coke. The thickness of the plastic zone set up in laboratory carbonization tests has been estimated (6) to be 6.35 mm. (0.25 inch). If the coal charge is heated from all surfaces, a more or less continuous envelope of plastic coal surrounding the unfused coal results. Under this condition, decomposition gases escaping inward may cause gaseous pressures to develop within the uncoked portion of the charge because the plastic envelope bounding this part of the charge is resistant to the flow of gas. This report gives the results of measurements of such pressures for low-, medium-, and high-volatile coking coals. They are termed "internal gas pressures".
