R@ACTIctNS OF THE3 ARSINES. ~CONTRIBWTIONFROM THE: CHZIICAE;
EACTIONS OF T
I,ABORhTORY
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OF TK€$Z'NIVZRSlTY OF ILLINOIS. ]
~ ~ E L ~ ~ I PAPER. N A ~ Y
BY ROGER ADAWSAND CHARLESSEATTUCK PALMER. Received August 16, i920.
The discovery of arsphenamine greatly stimulated research on organic a,rsenk compounds. The aim in these investigations has been not only to discover some substance with a higher therapeutic value but, more p a r t i c u ~ a rsome ~ ~ ~ substance of greater stability than arsphenamine. A large number of arsenic compounds have been prepared, but it is noticeable that most of them contain the arseno or arsenic acid groupings, namely, the same groupings which occur in those substances of proved t~erapeut~ value, c such as arsphenamine, sodium cacodylate and arrhenal. ~ ~ ~ ~ a r a t i little v e l yhas been done, however, in attempts to obtain arsenic linked In new ways in organic compounds to determine whe.ther the resulting substances might not be equal or superior therapeutically to those arsenic compounds already found valuable. The research, of which this is a preliminary report, had. such an object in view. A study of the condensation reactions of phenyl arsine with various organic reagents has been undertaken. The experiments have led to such interesting results that a number of investigations have been started to compare carefully the reactions of primary and secondary arsines and arsine itself with the corresponding nitrogen compounds. Experiments have also shown that tlse phosphines and stibines react similarly, so that a thorough study of these fields is to be taken up. The previous work on the reactions of the arsines has been very limited. It has been shown that halogens and alkyl halides react with primary and secondary arsines2 to give respectively arsine halides and arsonium halides, More recently a number of patentss have described the condensation of primary aryl arsines with aryl arsenious oxides or chlorides, with sryl stibinous oxides 01- chlorides, with arsenic, antimony or bismuth tx-ichiorides or tribromides. A more complete review and discussion of these reactions will be given in a future coinmrsnication. The present paper deals with t.he condensation of aldehydes with phenylarsine. Addition products are formed between 2 molecules of aldehyde and one molecule of arsine. The probable structure of the compounds produced is represented by the formula ia the following equation l This work was done under a grant from the U. S. Interdepartmental Social Hygiene Board, Washington, D. C., Dr. T.A. Storey, Secretary. z Bey., 34, 3598 (1901); Am. Chem. J., 33, I O X (1305); 35, I (1906); 40, 88 (1907). D. R. P., 254,187; Frdl. 11, x068 (1912-14); 275,216; 251,j71; 254,187; D.I?. P., zSa,ro4;253,226; 270,254; 269,699; 269,700:269,743; 269,744; 269,745.
BQGER ADAMS AND C€IAR€,lE3 SRSTTUCK PALXI$F,.
2376
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RCHO PiXsHz ----f (KCHOlI)2AsK. When the aldehyde and arsine are mixed, no apparent reaction takes place until a few drops of Iiyddochloric acid are added as a catalyzer Considerable heat is then gecerated and within a few minutes the reaction is complete. During this pliocedure, care mtrsl be used in haiidling the arsines as 44wg are easily 02cidi.4ed by the oxygen oE the air to alsennbenzene and phrnylarsinic acid. The condensation must be carried oiil in an atmosphere of crirbon dioxide 3r nitrogen. Up to the present time, ben:raldehyde and butyraldehyde have been :on$e:ised with phenylarsine. it seems probable that this reactiori m d , j be extended to any aromatic or aliphatic arsines and aldehydes. 'She compounds may be looked upon a5 corresponding somewhat t o aldehwde ammonias except that only one hydrogen atom on the iiitrogen atom reacts, whereas both hydrogen atoiiis on the arsenic atom take part.ii-r the change. The compounds, h o w \ el, in their chemical reactions do not resemble aldehyde amnwnias They are perfectly sCable in cold w 1076 sodium hydroxide 6;olution or dil. hydrochloric acid. Even after boiling them 5 minutes with these reagents, no decomposition takes place except with hydrochloric acid, and orrly a slight change occurs in ihis case. Other reactions of thcse substance5 vi11 he discirssed i ~ ia later paper. Whereas the compounds already made ale not solubie in mater, it i s hoped to obtain certain derivatives in this series which will be soluble it1 water and capable of therapeutic testing. ~ h e ~ i y l ~ Acid.-'l'his r s ~ ~ i ~ ubslance is prepared in 150-200 g. lots by a modification of Bart's reaction nhich was employed in Germany during the war.' It consists in the action of benzene diazonium chloride on sodium arsenite a t I 5 ' in the absence of free alkali and in the pr,nsence of a copper salt. The yields of ptrre, recrystallized acid are 40-50~4, calculated from the aiiiline. ~ ~ e ~ y l For ~ ~the~ preparation i n ~ ~ of z this primary arsine, phenylarshic acid in so g. lots is reduced m it11 amalgamated zinc du5t and hydrochloric acid. "lie yields obtained are 40-7oyo. Di-a-hydroxy-%-butyl phenylarsim ~ ~ ~ and~ ~z-bolgr~ y ehyde).--A 250-cc. arlenmeyer Aask is fitted with a 3-hole rubber stopper. A tube through which carbon dioxide may be passed into the fiiar;k is placed in one hole, an exit tube and a loo cc. separatory funnel in Lhe other boles. The air in the apparatus is completely replaced ay carbon dioxide, then 2 0 g. of phenylarsine is poured in through the funnel. This is followed by 5 or 6 drops of COLIC. hydrochloric acid, a i d , 5 r d l y y ID R P , 25a,o92, Erdl 11, 1030 (1913), J fnd. Eng Chem, I[*,825 (1919) Bar 34, 3598 ( r g o r ) , A m Ghem 1 , 3ss I (1906) ~
l
REACTIONS O F THE ARSINES.
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20 g. of n-butyraldehyde is added in small. portions. The reaction takes place immediately; enough heat is evolved to cause the mixture to boil, Carbon dioxide is passed in until the reaction mixture is completely cold (30 t o 40 minutes). The product is shaken out with 50 cc. of dil. sodium carbonate solution to remove phenylarsinic acid formed by the oxidation of phenylarsine during the manipulations, and then distilled under diminished pressure. The fraction boiling 226--230'~~mm. is collected and redistilled. Thus 18g. of product boiling a t 2 2 8 O Z 6 mm. is obtained. Although it boils very constant, the cold distillate is slightly turbid, probably due to a trace of phenylarsinic acid not removed by the sodium carbonate. It has the following constants: d3,,, 1.1r4; 1.686. The compound was analyzed for arsenic by a combination of methods. It was first burned by the method reported by Palmer1 in a current of oxygen in a tube packed with zinc oxide, the product then dissolved i n ~ C I I X . hydrochloric acid and precipitated with hydrogen sulfide. From this point, the procedure was the same as reported by Little.2 StlbS., 0.1966, 0 . 2 3 8 0 : coz, O.4IZO, 0.5027; HzO, 0.1371, 0.1602. Subs., 0 . ~ ~ 0 17.6 6 : cc. iodine ( I cc. sol. = 0.0031 g. arsenic). Calc. for C I ~ H ~ ~ O ~C, A Sj6.361 : R, 7 . 7 1 ; AS, 2 5 . 1 7 ~ Found: C, 56.47, H. 7.29, 7.53; ~ 4 % 24.74.
57.22;
This substance is a slightly volatile oil, readily soluble in organic solvents, but practically insoluble in water. It is a stable substance which remains undecomposed in cold water, I 0% sodium hydroxide solution and dil. hydrochloric acid. Even when boiled with these reagents, the substance seems to be stable to all except the dilute acid. i-or-hydroxybenzyl phenylarsine (Phenylarsine and Benzaldee).-The procedure for the preparation of this substance is similar t o the one just described. When 20 g. of phenylarsine, 29 g. of pure benzaldehyde and a few drops of hydrochloric acid are mixed, heat is evolved and within a few minutes the mixture has solidified. The crude product crystallized directly from benzene yields fine white needles with a constant m. p. of 193'. The compound must be dried t o constant weight a t 110' before it is analyzed. For the analysis for arsenic, the method of Erwins3 was used. Subs., 0.2187, 0.2163; & 1 0 2 , 0.5301, 0.4471; HzO, c.0895, 0.0709. Subs., o.zi63, 0.2296: iq.0 cc., r4.95 cc. iodine ( I cc. = 0.0031 g. As). Calc. for C ~ O H ~ ~ OC~, A65.58; S : R, 5 . r 9 ; As; 20.66. Found: C, 66.06, 66.28; H,4.33, 4.31;As, 2 0 . 0 7 , 20.19.
The substance is stable to water, dil. hydrochloric acid and in alkali. it i s soluble in most, organic solvents, but insoluble in water, 1
8
Palmer, Ber., 34, 3997 (1901). Little, .J. Chem. SOC.,95, 478 (1909). Ekwins, ibid., rog, 1356 (1916),
2378
GEORGE 13. I1OLH AND ROSS M K R N ~~R~~~~
I . ~ ~ ~ e n y ~has a rbeen s~~ eonitlensed e with ~ ~ t y r a ~ and ~ e ~h ~~ ~ ~~ e~ ‘lnyde to give compounds consisting oi t,wo moles of aldehyde arid one of arsine and probably having the fdpI1owing structure, ti i as(^^^^^^^^^. 2 The ~ ~ ~ ~ products e n sare ~stable ~ t~o i o~ ~ dilute ~d . ~ acid, alkali a.rd water.
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U R B A N A , ILLINOIS. _ _ . _ I _
[6ONTR.IF3PrTION’ FXOM
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AGRICULTURAL .@XPBRIIM?2NT STATXQW.
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YS BY GBORGGE. Ho Recei ed Aug, 28, 1920.
i n previous articles of this series2we have sl-rown ““tat the formation of black acid insoluble humin in a normal protein hydrolysate is dependent upon the presence of tryptophane in that protein molec~le.’~While tryptophan e reacts readily with aldehydes to give a black insoluble product, it alm ergoes some umknown reaction even when dlawed t o .st.and in an acid t h . This was noted by * ~ ~ d ~who r ~ fou.nd a ~thatd the ~ mother ~ ~ liquor from a tryptophane preparation, which had been allowed t o stand for a long time, slowly darkened, lost its ability to absorb bromine, gave no glyoxylic test, and finally deposited a dark brown produet, soluble in acids and alkalies, and which when heate gave a strong indole odor. Harries arid I,angheld* studied the effect, of ozone upon ~ y ~ r ~ ~ ~ ~ awith n eQ Z O K ~ ~ products of proteins and found that ~ r ~ ~ t o kre.ated colored very dark, gave no y loxylie reaction, reduced PehU ng’s ~ ~ ~ in the cold, was precipitat by baririm hydroxide, lead acetate, basic lead acetate, and liberated ammonia when treated with sodium ~ y ~ Van Slyke states5 “ ~ ~ y p ~ o ips ~known ~ n e to be precipitated ~ ~ ~ ~ t ~ by p ~ o s ~ h o acid ~ ~ even ~ i from ~ s ~fairly ~ ~dilute solution. When it is boiled with mineral. acids, Iiowever, it is, to a Barge extent, a t least destroyed, the nature and fate of the pro duet.^ being un1cnown.” In to ascertain the behavior of tryptophane under the conditions of p 1 Published with the approval of the Director as Paper No. 208, ’Jomiial Series of the Minnesota Agricultural Experiment Station. Presented before the Bioiiogical Division of the Rinerican Clzemical Society at the Spring Meeting, St. Lollis, WpriS
11-16, 1920.
Gortner and Rlish, THISJOURNAL, 3y1 1630-36 (191.5);Gortner, J . Biol. Cheherr,., (1916); Gortner and Holm, TEIS JOWR~M,, 39, 2477-2501 (~9x7);.#a, 82a-827 ( 1 9 2 0 ) ; Holm and Gortner, ibid., 42,632-40 (rgzo). Abderhalden, Z . physiol. Cirern., 78, rgy-160 (‘1912). Harries and Langheld, ibid., s a , 371-383 (1907). Van Slyke, S. B i d . CAem., IO, 39 (1911). 2
, 177-204
