These discourses were given with the aim of interesting the senior students of the medical school in the all-important but very much neglected subject of the history of medicine. With this as their aim it is quite sure they succeeded and it is indeed gratifying that there is an ever-increasing number of publications dealing with the past of this noble profession of medicine. The book is most readable and is well illustrated with forty-eight half tones, portraits of some of the masters of medicine. It could hardly fail to awaken the student unless he were entirely anesthetic to the subject.

Unfortunately Major Seelig did not go over his manuscript very carefully before publishing it, else he had not allowed so many errors to remain. The dates of the founding of the various universities are not in accord with the best authorities and the school of Salerno is referred to as a university. John Locke is placed in with the lights of the eighteenth century, when his dates are 1632-1704. Glibly he speaks of a group of English surgeons of the early nineteenth century as being familiar to American surgeons and almost of yesteryear. It would be interesting to know how many American surgeons could tell what Aston Key, Benjamin Travers, William Ferguson and James Wardrop did. They might make out better with the remainder of those mentioned-Astley Cooper, John Bell, James Syme, Robert Liston and Benjamin Brodie.

As we remarked before, the aim of the lectures is to be commended and those who listened to them of course caught the inspiration which was what was intended, but before being put into cold type they should have had careful revision.

BALTIMORE

JOHN RUHRÄH

SCIENTIFIC APPARATUS AND

LABORATORY METHODS

THE PRODUCTION OF PURE ABSOLUTE ALCOHOL WITH CALCIUM CARBIDE AND ANHYDROUS COPPER SULPHATE

EACH of the best known of the various processes, as described in the literature1-8 for producing absolute

1 Mendeleeff, Ann. Phys. Chem. 1869, ii, 138, 230. 2 Yvon, Compt. rend. 1897, 125, 1881-2. Ostermayer,

C. Bl. 1898, I. 658. Pharm. Ztg. 43, 99 9/2. 3 Kailan, Monatsch. 1907, 28, 927.

4 Winkler, Ber. 1905, 38, 3612-16.

5 Plucker, Zeit. Nahr u. Genussm. 1919, 17, 454-8.

6 Pozzi, Escat. Bull. Assoc. Chim. Sucr. Dict. 1909, 26, 580.

7 Chavanne, Bull. Soc. Chim. Belg. 1813, 27, 205. 8 Young, Trans. Chem. Soc. 1902, 81, 707 and 717.

alcohol on a laboratory scale from 94 to 95 per cent. alcohol presents one or more disadvantages, namely, expense of materials, time consumed, low yield or poor quality of product.

The use of calcium carbide as an alcohol dehydrating agent was proposed by Yvon.2 Approximately the first third of the distillate obtained under the conditions given contained acetylene. Ostermayer2 reports the successful production of absolute alcohol by the Yvon procedure, but emphasizes the difficult removal of the bad odor and taste of the distillate, due to organic sulphur compounds. These objectionable characteristics of the 100 per cent. alcohol so obtained have discouraged or prevented the use of calcium carbide as an alcohol dehydrating agent.

The authors have made an experimental study of the operation for the purpose of increasing the yield of 100 per cent. alcohol, reducing both the time and the quantity of carbide, and finding satisfactory means of removing the acetylene, organic sulphur and phosphorus compounds which are retained by alcohol when treated as Yvon directs.

The data from the following experiment will indicate the procedure and the conditions found most satisfactory:

Experiment III: To 100 gr. (92.34 wt. per cent., 95.02 vol. per cent., alcohol, contained in a flask attached to a reflux condenser, were added 17.5 gr. of granular, -20 mesh, calcium carbide (81.1 per cent. pure CaC2). The alcohol was maintained at boiling temperature on a water bath for thirty minutes, then 0.5-1.0 gr. of anhydrous copper sulphate was added, to engage the dissolved acetylene and sulphur compounds. Boiling under the reflux condenser was continued for fifteen minutes and the alcohol then distilled off.

Total distillate = 93.74 gr. or 98.66 per cent. of the theoretical yield. The specific gravity at 15 degrees C. = .7945 or 99.86 vol. per cent. alcohol, of normal odor and taste, and negative to tests for acetylene with Cu, Cl2, sulphur compounds, aldehyde and free

acid.

Qualitative tests for water in the alcoholic distillates were made with anhydrous copper sulphate, crystalline potassium permanganate and calcium carbide to determine the comparative delicacy of the reagents.

Anhydrous CuSO, is not nearly so delicate nor is a positive reaction as quickly obtained with it as with either of the other two. Potassium permanganate crystals showed faint pink after five minutes in 99.57 per cent alcohol-no color in 99.63 alcohol.

Powdered calcium carbide in 99.63 alcohol yielded E visible gas bubbles9 after a few seconds, while Kmn0, crystals showed no color after five minutes.

E

MANOILOV'S REACTION FOR IDENTIFICATION OF THE SEXES1

IN a recent number of the Russian Bulletin for Applied Botany and Plantbreeding two papers2 were published dealing with a problem which may have a great influence on the further development of studies on the physiology of sex. Since these papers deal with a subject in which many biologists are interested and since they are published in a periodical and language not very accessible to most of them it seems to us justifiable to give a short review of those papers and at the same time to present our tests of Dr. Manoilov's method.

Dr. Manoilov found a reaction3 by which it is pos

9 The calcium carbide used in a qualitative test should be freed from occluded air, as this, when alcohol is added, will give air bubbles which may be mistaken for acetylene gas bubbles. The discharge of occluded air will cease within a few seconds; the generation of acetylene, if water is present, will continue for a time.

1 Research carried on with the aid of a grant from the committee for research in problems of sex of the National Research Council.

2 Manoilov, E. O., "Identification of the sexes in dioecious plants by chemical reaction."' Bul. Appl. Bot. and Plantbreed. 13(2): 503-505. 1922-1923.

Grünberg, O., An addition to the paper of Dr. Manoilov: "Identification of the sexes in dioecious plants by chemical reaction.'' Bul. Appl. Bot. and Plantbreed. 13(2): 506. 1922-1923 (Both in Russian).

3 Manoilov's paper describing the method which he used in experiments with animals was published in Vratschebnaja Gazeta (Medical Gazette) No. 15, 1923. Unfortunately, it has not been possible for us as yet to obtain this paper.

sible to distinguish female blood from male. The following reagents were used:

(1) 1 per cent. solution of Papayotin in water. (2) 1 per cent. solution of Dahlia or Grübler's methylgreen in alcohol.

(3) 1 per cent. solution of potassium permanganate in water.

(4) 40 per cent. solution of HCl.

(5) 2 per cent. solution of thiosinamin in water.

To 3 cc of 10 to 20 per cent. blood 10 drops of the first solution were added, after one or two minutes 3 drops of the second solution, then 10 drops of the third, 1 to 3 drops of the fourth and 5 drops of the fifth solution were added. After additions of the first, second and third solutions the material has to be stirred (not shaken), and after the addition of the fourth and fifth reagents it has to be shaken. The male blood soon becomes colorless or nearly so, while female blood retains its reddish-violet color.

Dr. Manoilov is inclined to believe that hemoglobin is responsible for the differential male and female reactions he obtained, and since chlorophyll is chemically closely related to hemoglobin he tried to see if the same reaction would occur in dioecious plants. An alcoholic extract of chlorophyll from leaves was made by letting 10g of leaves stand for two hours in 30 cc of 60 per cent. alcohol. To 3 cc of that extract the same reagents were added in the way described above. Positive results were obtained, e.g., solutions from male plants became colorless and those from female plants retained the color. Experiments were made with Acer negundo, Lychnis dioica, Vallisneria, Urtica and Cannabis, all giving the same results.

Grünberg tested Manoilov's method on the following plants: Vallisneria sp, Urtica dioica, Cannabis sativa, Populus sp, Hippophae rhamnoides, Eucephialartos villosus, E. longifolius and Begonia sp. Especially interesting results were obtained with monoecious Begonia: male flowers gave the characteristic male reactions, female flowers gave the female reaction and the leaves an intermediate one. The experiments of Grünberg showed that the presence of chlorophyll is not essential for the reaction to occur. This was confirmed by the results of investigations conducted by Minenkov who obtained differential sexual reaction using seed and young seedlings of dioecious plants. Minenkov's method, however, was entirely different from that used by Manoilov.

Experiments to test Manoilov's method are being made by the authors, and positive results have been obtained with the following organisms:

4 Minenkov, A., Nautschno Agronomitscheskii Zurnal (Jour. Sci. Agr.), Vol. 1, 1924.

Mice

Sheep Pigeon

Fruit flies (Drosophila virilis)

Cladocera sp.

Salix sp.

Populus sp.

It may be noted that the reaction is very sensitive. A slight mistake in the method or fault in the material may give inconclusive results. It should be mentioned that nine more male mice than these previously listed were used in investigations. Six of them gave inconclusive results and with the other three a reaction was obtained which was classified as female. It is very likely that in those cases, due to our unfamiliarity with technic, reacting enzymes were destroyed and the expected reaction failed to

occur.

As pointed out by Manoilov in making the chlorophyll extract, it is essential not to have alcohol stronger than 60 per cent. and not to leave the material in alcohol over 24 hours. Otherwise the enzymes which produce the reaction are likely to be destroyed.

The authors are indebted to Dr. C. B. Davenport for mice and sheep material, to Dr. A. M. Banta for Cladoceras and to Dr. O. Riddle for pigeon material. SOPHIA SATINA M. DEMEREC

DEPARTMENT OF GENETICS

CARNEGIE INSTITUTION OF WASHINGTON COLD SPRING HARBOR, N. Y.

HYDROGEN-MAGNESIUM HALIDES1

THE intermediate formation of hydrogen-magnesium halides is postulated in current theories to account for the reducing action of the Grignard reagent on the carbonyl linkage. Several attempts have been made to prepare such compounds: first, the action of hydrogen halides on magnesium at low temperatures; second, the heating of sec-butylmagnesium bromide at 150° in a high vacuum, and, third, the catalytic reduction of RMgX compounds. Catalytic reduction of triphenylmethyl-magnesium chloride chloride gave results

which are indicative of the formation of hydrogenmagnesium chloride.

The reaction of RMgX compounds with azo compounds and the formation of colored intermediate compounds when the Grignard reagent reacts with carbonyl compounds suggests the intermediate forma

1 Abstract of a paper presented before the meeting of the American Chemical Society at Baltimore.

THE AMERICAN CHEMICAL SOCIETY1 The use of the sodium salt of dimethylglyoxime for the qualitative and quantitative determination of nickel: WALDO L. SEMON and GILBERT SWART. Dimethylgly oxime forms a crystalline hydrated sodium salt. It is extremely soluble in water and insoluble in alcohol. A 3 per cent. (0.1M) aqueous solution is recommended for use in qualitative and quantitative analysis to replace the 1 per cent. alcoholic solution of dimethylglyoxime. Analyses for Ni are given in the presence of Co, Cr, Mn, Zn and Fe and in various alloy steels.

Esters of 3-amino-4-hydroxymethyl-benzoic acid: FRANCIS H. CASE. Ethyl 3-amino-4-hydroxymethyl-benzoate is prepared as follows: p-cyanobenzyl chloride is nitrated, and the 3-nitro-4-chloromethyl-benzonitrile converted to the acetate. This compound on hydrolysis with alcoholic hydrogen chloride yields ethyl 3-nitro-4-hydroxymethylbenzoate. The latter is reduced to the amino ester by tin and alcoholic hydrogen chloride. Better yields were obtained with colloidal platinum in acetic acid solution. The butyl amino ester is similarly prepared from the butyl nitro ester. The hydrochlorides are soluble in water.

The local anesthetic action of these esters will be investigated. A simple method of preparing p-chloromethyl benzoic acid has been found, in which the corresponding nitrile is hydrolyzed with conc. HCl, and the acid recrystallized from alcohol; yield, 80 per cent. On attempted recrystallization from water, p-hydroxymethyl benzoic acid results. Under the same hydrolytic conditions p-cyanobenzyl bromide is also converted into p-chloromethyl benzoic acid.

The reactivity of the hydroxyl group in certain alcohols: JAMES F. NORRIS and HENRY D. HIRSCH. The reactivity of the hydroxyl group in nine straight chain aliphatic alcohols was measured by determinations of their rates of reaction with aqueous hydrobromic acid at 100°. The rates were found to be related in a quantitative manner to the structure of the alcohols.

If a

1 The Los Angeles Meeting, August, 1925, of the Divisions of Organic Chemistry and of Medicinal Products.

hydrogen in each position relative to the hydroxyl group be assigned a certain number, called the reaction number, then the reaction constant for any of the nine alcohols can be found simply by finding the total of the reaction numbers of all the hydrogen atoms in the molecule. Designating the H on the carbonol carbon as “'a,' "the next as "b," etc., we find that the reaction numbers of the hydrogen atoms are as follows: position a, .000109; b, .000015; c, .000066; d, .000010; e, .000045. Thus the reaction constant of n-propyl alcohol is 2x .000109 + 2 x .000015 + 3 x .000066 = .000446. The experimental values were found to check the calculated values within a few per cent.

The behavior of acetylene and cuprous chloride catalysts in an ammonia system. II: EUGENE WILLIHNGANZ and J. A. NIEUWLAND. Acetylene condenses with aniline in the presence of the chlorides of copper or mercury to form a substance thought to be a polymer of ethylidine aniline. When this is heated in the presence of a small amount of acid, rearrangement takes place with the formation of products similar to those obtained by the action of aldehyde on aniline. Quinaldine and hydroquinaldine are present. N-ethyl aniline has been isolated, as also o- and p-ethyl anilines. Lepidine and gamma-methyl quinaldine are probably present as evidenced by reaction products. A new explanation of the mechanism of the Skraup synthesis of quinoline is offered.

actions. The methyl and ethyl esters are the most active and give the muscarine effect greater than does either choline or murine. This change of activity brought about by muzzling the hydrogen atom of the carboxyl group through esterification is believed by the authors to give further evidence for the idea that to show these activities the substances must have (1) a definite spacial configuration and (2) they must exist in the blood stream as cations. On this theory the inactivity of betaine is explained by its existence in the blood as the electrically inert inner salt [bipolar ion, + (CH2),N – CH2COO-].

Studies on the formation of condensation products of furfural: S. A. MAHOOD. Condensation products of furfural are more difficult to obtain than those of benzaldehyde, due to the greater tendency of the former to polymerize. Benzene and furfural in the presence of zinc chloride give an insoluble solid polymer of the aldehyde but no diphenyl-furyl-methane. Attempts to make the latter through the fural halides led to similar polymerization products. With aryl amines, however, furfural condenses under the influence of inorganic acids or zinc derivatives, depending upon the conditions under which the condensation is brought about and the type of the amine used.

The preparation of l-arabinose from mesquite gum: ERNEST ANDERSON and LILA SANDS. Arabinose is readily prepared by the hydrolysis of mesquite gum for three hours at 80° in six times its weight of 4 per cent. sulfuric acid. After removal of the acid as barium sulfate the neutral solution is concentrated, the salts precipitated by alcohol, the alcohol solution of the sugars concentrated and allowed to crystallize. The yield of crystalline sugar varies from 27 to 36 per cent. of the gum used. sugar can be recrystallized from water, mixtures of water and alcohol or from glacial acetic acid. Mesquite gum can be purchased in large amounts in the southwest.

The

The ultra-violet absorption spectra of N-methyl-gammapyridone, gamma-pyridone, pyrone and related compounds: E. RAYMOND RIEGEL and MELVIN C. REINHARD. The absorption spectra of nine bodies, which fall in three groups, have been studied: Group A: N-methyl-gammapyridone, gamma-pyridone, pyrone. Group B: N-methyl chelidamic acid, chelidamic acid, chelidonic acid. Group C: N-methyl-gamma-oxy-piperidine, gamma-oxy-piperidine, tetrahydro-pyrone. A quartz Hilger sector spectrophotometer was used, with a spark under water giving a continuous source of light; the solvent was water in each The molecular extinction coefficient was plotted against wave lengths. All the members of group A and group B give selective absorption; those of group C are almost transparent. The persistence of the band for the members of group A is of the same order of magnitude; this is true also for group B; the average persistence for group A is three times the average for group B. Various observations of the effect of substitution of N-H for N-CH, and for O and of the introduction of the two carboxyl groups are made; previous investigations are re

case.

viewed, and the bearing of the results on the present theories of light absorption is discussed.

Studies in vapor pressures. II. The mono-nitro toluenes: J. F. T. BERLINER and O. E. MAY. The vapor pressures of the ortho and meta nitro toluenes have been measured from 50° C. to temperatures slightly above their boiling points at atmospheric pressure, using the method devised by Smith and Menzies. Their latent heats of vaporization were determined by utilizing the ClausiusClapeyron equation of state. The vapor pressures were also calculated and were in close agreement with the observed values. The entropies of vaporization have been derived.

Pyrogallolsulfonephthalein, 2, 3, 4-trihydroxybenzoylbenzene-o-sulfonic acid (the intermediate acid) and some of their derivatives: W. R. ORNDORFF and N. FUCHS. Pyrogallolsulfonephthalein was made by heating 2, 3, 4-trihydroxybenzoylbenzene-o-sulfonic acid either alone or with pyrogallol. It was also made by heating (1) saccharin, (2) the chlorides of o-sulfobenzoic acid and (3) the anhydride of o-sulfobenzoic acid with pyrogallol. When heated to 200° the derivatives of pyrogallolsulfonephthalein are converted into the corresponding derivatives of sulfonegallein by the loss of a molecule of water of constitution. Pyrogallolsulfonephthalein, its dibromo derivatives and sulfonegallein react as tautomeric substances forming colored derivatives of the quinoid form and colorless derivatives of the lactoid form. Pyrogallolsulfonephthalin and its zinc salt were made.

With

The mechanism of addition of halogens to double bonds: A. W. FRANCIS. In neutral aqueous solution, bromine and unsaturated compounds produce chiefly bromohydrin compounds, but this is not due to hypobromous acid. It can be prevented by a high concentration of neutral bromide or chloride, giving respectively the dibromo- and the chlorobromo-compounds. sodium nitrate and bromine, ethylene gives some bromoethyl nitrate. Iodine gives similar mixed derivatives using sodium chloride or bromide. It is suggested that the halogens dissociate to some extent in aqueous solution, e.g., to Br+ and Br-. The former is "nascent bromine,'' and reacts with the unsaturated compound forming a positive radical (RCHBrCHR'—)+, which then may combine with any negative ion such as OH-, Br, Cl-, NO, ̄.

The chlorination of vanillin and derivatives of chlorovanillin: RAYMOND M. HANN and G. C. SPENCER. Vanillin is readily chlorinate in glacial acetic solution, the chloro-vanillin separating out in part in brilliant colorless tetragonal crystals. The analysis of the compound indicates it is a monochloro substitution product, chlorine entering the 5 position, adjacent to the hydroxyl group. Derivatives were prepared-the oxime, hydrazide, phenyl hydrazide, semicarbazide; the semicarbazide and diphenyl hydrazide are all beautifully crystalline solids. Condensation with ethyl cyano-acetate yields ethyl alpha-cyano3-methoxy-4-hydroxy-5-chloro-cinnamate. Upon hydroly

sis with concentrated HCl this yields 3-methoxy-4-hydroxy5-chloro-cinnamic acid.

The optical identification of the naphthalene sulphonic acids by means of their benzyl-y-thiourea salts: RAYMOND M. HANN and GEORGE L. KEENAN. The optical properties and indices of refraction of analyzed benzyl-y-thiourea salts of alpha and beta mono-naphthalene sulphonates and 1, 5: 1, 6:2, 6: and 2, 7 di-naphthalene sulphonates were determined. These constants give a means of identifying the various acids, not only when isolated, but also in mixtures. A diagnostic table was prepared showing a ready means of determining which acid of the series is present by successive immersion in two refraction liquids. Photomicrographs showing the appearance of the various salts were also prepared.

The chlorination, iodination and nitration of dihydroxytriphenyl methane-o-carboxylic acid: RAYMOND M. HANN and S. F. ACREE. Dihydroxy-triphenyl methane-o-carboxylic acid was chlorinated to yield a tetrachloro acid by treatment with chlorine in cold glacial acetic acid. The compound yields a diacetate with acetic anhydride, a dibenzoyl derivative with benzoyl chloride and a hexachloro-triphenyl methane-o-carboxylic acid with phosphorous pentachloride. Dihydroxy-triphenyl methane-ocarboxylic acid gives a tetra-iodo derivative with iodine in the presence of strong reducing agents. Dihydroxytriphenyl methane-o-carboxylic acid yields a di-nitro derivative upon treatment with HNO,. Experiments upon the oxidation of these derivatives with dilute potassium ferricyanide are now in progress.

The condensation of aldehydes with diphenyl iso-thiohydantoin: RAYMOND M. HANN and KLARE S. MARKLEY. Diphenyl iso-thiohydantoin is condensed with various aldehydes--salicylic, chlorosalicylic, bromosalicylic, iodosalicylic, vanillin, iodo-vanillin, bromo-vanillin, chlorovanillin, nitro-vanillin, iso-butyric and other aldehydesand the products purified and analyzed. These derivatives are to be used in studies of reduction products and in spectrophotometric studies.

The toxicity of local anesthetics (with special reference to apothesine): HERBERT C. HAMILTON. A substitute for cocaine should be not only effective and non-habit forming, but should be relatively much less toxic. Toxicity tests should be based on the ordinary use of the material in clinical practice, but in addition such tests should be made as will show the possible results from accidental or unusual forms of administration. Apothesine has been tested for toxicity in comparison with cocaine by subcutaneous, intravenous and intraperitoneal injections, and the effect of adrenalin is described, by which the latter acts as an antidote. Previous work is reviewed to demonstrate the comparative effectiveness of apothesine and cocaine.

NORTHWESTERN UNIVERSITY, EVANSTON, ILLINOIS

FRANK C. WHITMORE, Secretary