BECKETT AND WRIGHT ON THE ACTION ETC. IV.-Action of the Organic Acids aid their Anhydrides on the Natural Alkaloids. Part 11. Butyry 1 and Benzoyl derivatives of Morphine and Codeine. By G. H. BECKETT D.Sc. (Lond.) and C. R. ALDERWRIGHT Lecturer on Chemistry in St. Mary's Hospital Medical School. 8 1. Actioiz of Ezctyric Acid ow Codeirte. When anhydrous codeine and twice its weight of butyric acid are gently boiled together for five or six hours dihutyql-codeiize is formed in virtue of the reaction- C36H42N206 + 2( C&O.OH) = 2H20 + C36H,0(C&O)2N206. On evaporating off the excess of acid on the water-bath dissolving the residue in water and adding sodium carbonate a tarry mass is pre-cipitated which must be dissolved in dilute hydrochloric acid and repre- ciyitated by sodium carbonate to remove any traces of unaltered codeine mechanically carried down.The ethereal solution of the purified base does not crystallise by spontaneous evaporation even when a crystal of some analogously constituted body (e.g. diacetyl-codeine) is added to the saturated solution the dibutyryl-codeine only making its appearance as a varnish-like mass ; even when the base was regenerated from a speci- men of hydrochloride purified by several recryst,allisations it was found impracticable to obtain it in a crystalline condition by any means what- ever. On adding hydrochloric acid to the varnish-like base or to its ethereal solution a well-crystalliseil hydrochloride is produced ; of this 1.545 gram dried in blotting-paper lost at 100" 0.183 gram = 11-84? per cent.The formula C3sH,o(CaHTO) 2N206,2HC1,6H20,requires 11.75 per cent. 0.2730 gram of hydrochloride dried at 100" gpve 0.6535 CO and 0,177 H20. 0.4280 gram of hydrochloride dried at 100" gave 0.1510 Ag(311. 16 BECKETT AND WRIGHT ON THE ACTION OF THE Calculated. Found. C44 528 65.11 65.28 H56 56 6.91 7.20 c12 71 8.75 8.73 NZ 28 3.45 - 08 128 15.78 - - C36H43( C*H,O)JY2O,.2HCl 811 1OO.OO - The platinum salt gave the following numbers :-0.5370 gram gave 0.0920 Pt = 17.13 per cent. The formula C,SR~O( C,H,o)2N206.2HC1.Ptc14 requires 17-18 per cent,. Dibutyryl-codeine differs from diacetyl-codeine not only in being non-crystalline (the latter base being most readily crystallised from ether) but also in the amount of water of crystallisation taken up by the hydrochloride the former base yielding a salt containing six pro-portions of water while the latter contains only four.tj 2. Action of Butyric Amhydride OW Codeine. From the former results obtained with acetic acid and anhydride it would appear a priori probable th ' butyric anhydride would yield the same dibutyryl-codeine as that obtained by the action of butyric acid ; and in point of fact this is the case by heating codeine to 140" with excess of butyric anhydride the dibutyryl-codeine above described is produced. The hydrochloride obbained as above described gave the following numbers :-1.144 gram dried in blotting-paper lost at loo" 0.1480 gram = 12.94 per cent.The formula C3sH,o( C,H,o),N,o6.2HCt.6H,o requires 11-75 per cent. 0.3185 gram of platinum-salt gave 0.0550 Pt = 17.26 per cent. Calculated percentage = 17.18 per cent. All attempts to obtain the free base in the crystalline state proved fruitless. 5 3. Actioiz of Butyric Acid on Morphine. When anhydrous morphine is heated to 130" or higher for 5-43 hours with twice its weight of butyric acid a reaction occurs precisely similar to that produced by the action of acetic acid (Part I) viz. :-CaH3sN,Os + ~(C~HTO-OH) = 2HZO + C,H3s(C,H,O),NZO, *he only difference observable being that the hydrochloride of the resulting dibutyryl-morphine is far more soluble and crystallises less readily than that of the corresponding a-diacet,~l-rnorphirie.ORGANIC ACIDS AND THEIR ANHYDRIDES ETC. On treating the product of the reaction with ammonia or sodium carbonate and ether an ethereal solution is obtained which if evapo- rated quickly dries up to a variiish-like mass ; by slow spoiitaneous evaporation however crystals are sometimes formed and on bringing a crystal so produced into contact with the sticky resinous product formed in other cases the whole becomes crystalline. The crystals thus produced appear to be anhydrous when air-dry. They lose in weight slightly at loo" however apparently from decomposition. In three experiments 0.22 0.& and 0.51 per cent. was thus lost whilst the dried substances gave on aiialysis numbers slightlyin excess of the calculated values.After several recrystallisations from ether dibutyryl-morphine gives no coloration with ferric chloride ; it is however difficult to arrive at this state of purity as a small quantity either of some decomposition- product formed on standing or of some substance formed simultaneously with the dibutyryl morphine (P-dibutyryl morphine ?),pertinaciously adheres to the crystals and communicates to them the power of striking a faint blue with ferric chloride. The following numbers were obtained after drying at 100" :-Specimen A. 0.3030 gram gave 0.7935 CO and 0.2020 H,O. , 13. 0,3240 gram gave 0.8530 CO and 0.2230 HzO. Calculated. Found. (-4.) (BJ C42 504 71.00 71.43 71.80 He0 50 7-04 7.41 7.64 -I NZ 28 3.94 128 18.02 -08 __-_ -~ C34H36( C4H,0)2NzOs 710 100nOO When exactly neutralised with dilute hydrochloric acid this dibutyryl-morphine forms a syrupy liquid which sonietimes dries up to a gummy mass without crystallising and sometimes solidifies to a mass of radiating crystals very soluble in water.The same behaviour has also been noticed in the case of tetracetyl-morphine hydrochloride. After drying at 1000 the following numbers were obtained; the slight excess of carbon found denoting a minute amount of decomposi- tion just as with the free base :-0.6020 gram gave 0.2190 AgCI. 0.6390 , 0.2330 , 0.4490 , 1.0645 CO and 0.2725 K,O. Tor.. XXVTTI. C BECKETT AND WRIGHT ON THE ACTION OF THE Calculated. Found. C42 504 64.37 64.65 Ha2 52 6-64 6.74 CL 71 9.07 8.99 9-02 NZ 28 3.5 7 08 128 16-35 C3aH,,(CaH,0)zN,06.2HC1 783 100'00 The platinum salt gave the following numbers :-0.5970 gram gave 0.1055 Pt = 17.67 per cent.The formula c3,H3,(CaH,o),N,06.2HC1.PtCl requires 17.60 per cent. The ethereal mother-liquors from which the dibutyryl-morphine has separated contain a small quantity of a non-crystalline base which gives a blue coloration with ferric chloride probably this is the butyryl correlative of the analogous product formed together with a-diacetyl morphine by the action of acetic acid on morphine (Part I.). Separated as far as possible from the crystalline base by spontaneous evaporation almost to dryness rubbing up with a few drops of absolute alcohol (which only dissolves the crystalline base slowly) and quick filtration a viscid liquid was obtained which utterly refused to cry-stallise ; converted into platinum salt it gave the following num- bers :-0.6545 gram gave 0.1130 Pt = 17.27 per cent.Calculated for Cd3&(C4H,O),N2O6 2HC1 PtC14 = 17.60 , Hence it appears that this non-crystalline base is isomeric with the crystalline one in a,ll probability the two are the butyryl correlatives a-and P-diacetyl morphine respectively. § 4. Action of Bzctyric Aizhydride OTL Morphine. Anhydrous morphine was heated to 140"for three hours with twice its weight of butyric anhydride ; the product was dissolved in warm water filtered from a little tarry decomposition-product and precipi- tated by sodium carbonate the precipitate on treatment with ether yielded an ethereal solution from which no crystals could be obtained by evaporation a varnish-like mass only resiilting like dibutyryl codeine ; unlike this product however the base tetrabzctl/r~Z-morp7~~~ e refused to yield a crystalline hydrochloride ; the neutraZ solution of the hydrochloride drying up to a gummy mass differing from the hydro- chlorides of a-diacetyl-morphine only in that it gave no blue colora- tion with ferric chloride.The following numbers were obtained ORGANIC ACIDS AXD THEIR DERIVATIVES ETC. 0.3270 gram gave 0.7745 C02and 0.2120 H,O. 0.3340 gram treated volumetrically gave 0.0301 GI. 0.5430 grain of a different specimen treated volumctricdly pve 0.0422. Calculated. Fouiid. 600 65-01 64.60 c50 HGt 64 6.93 7.20 CI2 71 7.69 7-64 7-77' 28 3.03 -N2 010 160 17-34 --_--C34H34(CaH,O)J2OG.2HC1 3.33 100.00 Converted into platinum salt the following numbers were obtained :-0.7295 gram gave 0.1150 gram Pt = 15.76 per cent.The formula C,,H,,( C4H70),N2O6. 2HC1.PtCIA requires 15.65 per cent. 9 5. Action of Water0% I~tr~bzcty~~l-?nor~~~ne. It has been shown in Part I that tetracctyl-morphine on boiling with water breaks up tlius :-C~~HN(C~H~O)~NZO~ + 2H2O = 2(C&LO.OH) + C3aH34 C2H30)2N20 forming the same diacetyl morphine (the a-modification) that is produced by the action of acetic acid on morphine. Przcisely the same result is produced in the case of tetrabutyryl-morphine with this difference that the action is very much slower and that in order to facilitate it, it is necessary to use a mixture of alcohol and water (about equal bulks) so as to retain the base in solution.Even then 12 hours' or more incessant boiling (with an inverted condenser attached) is required before any considerable amount of dibutyryl-morphine is formed. On distilling off the alcohol an aqueous liquor is obtained containing the butyrates of dibutyryl-morphine and morphine (the lattei. generated by the further splitting up of the dibutyryl-morphine) and a tarry preci- pitate of unaltered tetrabutyryl-morphine this is filtered off and trreated over again. On treating the aqueous solution with Roctiurn carbonate and ether an ethereal solntion is obtained fi-om which dibutyryl-morphine may be obtained in crystals by slow spontaneous evaporation.This base appears to be in all respects identical with that formed by the action of butyric acid on morphine ; the base when suffi- ciently purified gives no coloration to ferric chloride. By spontaneous evaporation its ethereal solution deposits crystals which appear to be anhydrous but which lose a small amount on heating to loo" just as c2 BECKETT AND WRIGHT ON THE ACTION OF THE the product from the action of butyric acid on morphine probably from incipient decomposition after drying at 100'-0.5370 gram gave 0.8850 GOz and 0.2290 H?O. Calculated. Foulla. C4z 504 71.00 71-62 H60 50 7.04 7.55 N2 28 3.94 - 08 128 18.02 - - C34H36(C4H70) 2N2Os '710 100.00 The hydrochloride in one experiment dried up to a non-crystalline gum in another to a mass of radiating crystals very soluble in water ; the platinum salt gave these numbers- 0.7700 gram gave 0.1350 Pt = 17.53 per cent.The formula C~,H~(C4H70)zNzOs,2HC1.PtC1,,requires 17.60 per cent. 8 6. Acety1-bu(tyry1-morphirze. When anhydrous morphine is boiled for several hours with twice its weight of a mixture of equivalent quantities of acetic and butyric acids acetyl- bu tyryl-morphine is generated in virtue of the reaction- C34H38N206 + C2HSO.OH + CaH,O.OH = 2HzO + c34H36(C2H3O) (C4H7O)NzOs. On treating the product with sodium carbonate and ether and agitating the ethereal solution of the base with enough hydrochloric acid to form a neutral liquid a copious supply of crystals was obtained notably more soluble in water than a-diacetyl morphine hydrochloride ; after drying at llOo,they gave the following numbers :-0,5695 gram gave 0,2185 AgCl chlorine = 9-49per cent.The formula C34H,( C,H,O) (C4H70)NzO6.2HC1 requires 9.40 per cent. These crystals were recrystallised from boiling water ; but unfortu-nately it was found that they were decomposed by the treatment ; cry-stals were deposited on cooling consisting chiefly of a-diacetyl-morphine hydrochloride whilst the mother-liquors contained much of a very soluble butyrylated morphine after three successive recrystallisations from hot water the crystals finally obtained were nothing but a-diacetyl- morphine hydrochloride ; they lost at 120° 13.35 per cent.the ca1- culated amount (for 6H20) being 12.93; and on saponification by potash and distillation with enough sulphuric acid to liberate just half ORGANIC ACIDS AND THEIR DERIVATIVES ETC. the acid thus formed a distillate was obtained from which a barium salt was formed containing Barium . . . . . . . . . . . . . . . . 53.5 per cent. Calculated for acetate . . . 53.7 , Had any acetyl-butyryl-morphine been present in the crystals this barium salt would have contained all the butyric acid formed on saponification. In another experiment where a mixture of acids in which butyrio acid greatly predominated was employed a product was formed from which a crystalline hydrochloride was isolated as before ; this gave the following numbers after one recrystallisation from warm (not boiling) water :-0.9995 gram of air-dry salt lost at loo" 0.1590 = 15.91 per cent.The formula C34H,(C2H30) (C,H,0)Nz06.2HC1.8H20 requires 16.02 per cent. 0-314.5gram of dried substance gave 0.7280 COz and 0.1835 H,O. 77 3, 0.4615 , , 0.1765 AgCl. 9, 0.3775 , , , 0.1445 , 0.4730 , fiubstance dried at 120" gave 0.1795 AgC1. Calculated. Found. C40 480 63.58 -63.13 -His 48 6.36 -6.66 -C1 71 9.40 9.46 9-47 9.39 N 28 3.71 --08 128 16.95 --~ ---C34H3,( C2H30) (C,HyO)N,O+ZHCl 755 100eOO The neutral liquid from which these crystals separated in the first instance dried up to a gum-like mass wbioh gave a blue coloration with ferric chloride and contained- Carbon 63.75 ; chlorine 9.16 per cent.Dibutyryl morphine requires carbon 64.37 ; chlorine 9.07 per cent. from which it appears that as might be expected the excess of butyric acid present gave rise also to dibutyryl-morphine or a mixture of isomeric dibutyryl-morphine. 8 7. ActiorL of Bewzoic AdLydride otL Codeim. Codeine was heated to 130" for four hoiirs with rather more thaii its own weight of benzoic anhydride the product dissolved sparingly in hot water somewhat more readily in hot very dilute hydrochloric acid. The warm opalescent solution was precipitated by oarbonate of soda ; the precipitate was dissolved in warm diluie hydrochloric acid BECKETT AND WRIGHT Oh' THE ACTION OF THE and again precipitated with sodium carbonate ; and this precipitate was dissolved in ether.The ethereal solution gave on evaporation a copious crop of anhydrous crystals which yielded the following numbers on combustion :-0.3110 gram gave 0.8525 GO and 0.1780 H,O. Calculated. Foun& c50 600 74.44 74.76 H5o $0 620 6~36 NZ 28 3.48 -08 128 15.88 -C,6R,(C,H,O)~N20 806 100*00 This base dibenzoyz-codeiwe is very sparingly soluble in water both cold and hot ; from a large bulk of boiling water it can be cryshllised unchanged; when it is dissolved in very dilute warm hydrochloric acid a clear solution is obtained ; on cooling this salt does not deposit crystals but becomes an opalescent gelatinous mass much resembling starch- paste or gelatinous silica ; from it strong solution the hydrochloride separates as an amorphous tarry mass it is however possible to obtain the hydrochloride in crystalline form by dissolving it in dilute slightly warm alcohol and leaving the solution to cool slowly with con- stant stirring and kubbing the crystals thus produced gave rise to nothing but a gelatinous mass when dissolved in warm water and allowed to cool.Dried in blotting-paper and exposed to the air until a constant weight was attained they gave the following numbers :-1,027 gram of air-dried substance lost 0,043gram = 4.18 per cent The formula C36H40( C,H,o),N,06.2HCl.2H20 requires 3.93 per cent. The anhydrous salt gave the following numbers :-0.34-20gram gave 0.8530 C02 and 0.1990 H,O. 0.2800 gram estimated volumetrically gave 0,0225 C1. 0.2990 gram gave 0.0970 AgCl.Calculaked. Found. Go 600 68.26 68.02 -a2 52 5.92 6.47 -71 8.08 8.03 8.03 N2 28 3.18 -138 14-56 -08 C36H,(C,H,O),N2Os.2HCl 879 IOO*OO The platinum salt gave the following numbers :-0.3080 gram gave U*0500 Pt = 16-23 per cent. 1,c ORGAKIC ACIDS AND THEIR DERIVATIVES ETC. The formula C36H4,( C,H,o),N2o6.2HC1.PtCl4 requires 16.21 per cent. This platinum salt like the benzoylated morphine products described in the next sections differs from the acetylated platinum salts and most platinum salts of morphine and codeine derivatives in being much more readily soluble in alcohol than in water the converse being usually the case. 9 8. Action of Bensoic Anhydride on 2Cfoyphine. Morphine was heated to about 130"for three or four hours with twioe its weight of beneoic anhydride ; the product dissolved in hot dilute hydrochloric acid was precipitated by sodium carbonate and treated with ether ; on evaporation anhydrous crystals of tetrabenzoyl-morphine seprated these gave no colour reaction with ferric chlo- ride.0,2960 gram gave 0.8220 GO and 0.1530 H,O. Caloulated. Found. c 744 75.46 75-73 H54 54 5.47 5.74 NZ 28 2.84 -160 16.23 -010 CS*HsP( C7H,O)aN,06 986 100.00 The hydrochloride of this base is very sparingly soluble in oold water ; it possesses properties precisely similar to those of dibenzoyl-oodeine saving that no artifice has hitherto been successful in obtaining it in a ci-ystallised condition. 0.4775 gram gave 0.0312 gram C1 (volumetric).0,3810 , , 0.9845 COz and 0.2000 H20. Calculated. Found. C6-2 744 70.26 70-47 H5s 56 5-29 5.83 C12 71 6-70 6-53 N2 28 2.64 -010 160 15.11 -C34H34( C,H6O)JJaO6.2HCl 1059 IOO*OO The platinum salt made by adding platinic chloride to it warm aqueous solution of the salt gave these numbers :-0.2440 gram gave 0.0345 Pt.. . . . . . . . . . . . . . . . . . . = 14-14per.cent. The formula C3aH3i(C,H,0)4N,O,.2HCl.PtC14 requires 14.13 ~~ BECKETT AND WRIGHT ON THE ACTION OF THE § 9. Action of Water on TetraDeiLxoyl-?7aorp~ine. Tetrabenzoyl morphine is somewhat less readily acted on by boiling water than tetrabutyryl-morphine (which as above shown is less readily attacked than tetracetyl-morphine) ; when boiled with a mixture of about equal volumes of alcohol and water as described in § 5 for 48 hours consecuti-oely it partially undergoes the following reaction whereby dibeneoyl-morphine is generated apparently identical with that formed by the direct action of benzoic acid on morphine (§ 10).The production of benzoic acid in this way was verified by treating the resulting liquid (after distillation of alcohol) with hydrochloric acid and ether when benaoic acid was dissolved out giving the ordinary qualitative tests. Carbonate of soda threw down from the acidified solution a small amount of precipitate ; on agitating this with ether an ethereal solution was obtained which yielded a mixture of the hydrochlorides of te trabenzoyl- morphine and dibenzoyl- morphine ; the latter crystallised in minute crystals on cooling the slightsly warm aqueous solution ; it wag however found difficult to obtain this free from tetrabenzoyl-morphine hydrochloride which does not crystallise forming a tarry mass ; the platinum salt finally obtained gave the fol-lowing numbers showing that a small quantity of tetrabenzoyl-mor-phine platinochloride was also present.0.8805 gram gave 0.1400 gram Pt = 15.90 per cent. Dibenzoyl morphine platino-chloride rcquires i6.60 , 3, Tetrabenzoyl > 7 14-13 p7 0 10. Actiorb of Beiizoic Acid on dIoryliii$e. Anhydrous morphine was heated for seven hours to about 160" with twice its weight of benzoic acid ; the product was dissolved in warm dilute hydrochloric acid and precipitated by carbonate of soda (which only gave a very trifling precipitate morphine being not instantaneously thrown down by this reagent at any rate from solutioiis not too con-centrated).On treating the mass with ether a minute portion was dissolved ; the ethereal solution yielded a tarry mass on agitation with a few drops of hydrocliloric acid and this when dissolved in hot water gave white crystals on cooling yery sparingly soluble and apparently identical with those described in the previous section. The quantity of these being too small for experiment they were converted into platinum salt of which 0.4005 gram gave 0.0670 Pt = 16.73 per cent. The formula C3iH3F(C,H,0)2N206.2HC1.PtCla requires 16.60 , ORGANIC ACIDS AND THEIR DERIVATIVES ETC. The crystals of hydrochloride gave no blue colouration with ferric chloride whence it seems that benzoic acid acts to a minute extent like acetic acid giving rise to a-dl:be.naoyl-molplaine thus-C34H38NZO6 + 2(C,H&.OH) = 2HzO + C34H3,( C,H,O),N,Os.§ 11. Action of Benaoic Anhydride on a-Diacetyl-morphine. Anhydrous a-diacetyl-morphine was heated with rather more than its own weight of benzoic anhydride to 150" for about three hours. The product treated with sodium carbonate and ether gave an ethereal solution which refused to crystallise spontaneously by slow evaporation only forming a gummy varnish; by rubbing the side of the vessel,' however with a glass rod to which a minute fragment of crystalline tetrabenzoyl-morphine adhered crystallisation was set up and a copious supply of anhydrous crystals of a new base a-diacetlll-dibenxoy 1-nzor-phine separated.0.3300 gram gave 0.8770 CO and 0.1910 H20. Calculated. Found. C52 624 72.39 72.48 H50 50 5-80 6-43 N2 28 3-25 010 160 18.56 - - __I-p- C,aH,,( C2H3O),(C7H,O),N,O6 862 100.00 This base gives no colour reaction with ferric chloride ; when treated with dilute hydrochloric acid it forms a hydrochloride pretty readily soluble in pure water but precipitated therefrom as tarry flakes by addition of hydrochloric acid ; all attempts to crystallise this salt have hitherto proved fruitless. The following numbers were obtained :-0.4140 gram gave 0.1310 AgCl chlorine = 7.83 per ct. The formula C,H3,( CzH30)z(C7H,0)zNz0,.2HC1 requires 7.60 , The platinum salt gave the following numbers :-0.1435 gram gave 0.0225 Pt = 15.68 per ct.Calculated for C34Hs(CZH30),( C,H,O),NzO,.2HCl.PtC1 = 15.50 , § 12. Action of Benzoic and Acetic Adagddes on Illetl.a-nc~tyl-mor~hine a11 d TetrccbemoIJ 1-morphirk e respective1y . In order to see if it mere possible to displace benzoyl by awtyl or vice i~rsd,in these derivatives each base was heated to about 130" for four hours with 3 to 4 times its weight of the required anhydride. In neither case however was any marked amount of action noticeable. Bci BECKETT AND WRIGHT ON THE ACTlON ETC. The product of the action of benzoic anhydride on tetracetyl morphine was precipitated by carbonate of soda and treated with ether ; by syon-taneons evaporation crystals were formed.A portion of these crystals and the last few drops of mother-liquor (representing about one-twentieth of the whole) were converted into platinurn salts and examined with the following results :-0.3585 gram of salt from crystals gaye 0.0620 Pt = 17-29p.c. 0.5040 , , mother-liquors gave 0.0830 16.46 , Tetracetyl-morphine platinochloride requires 17.17 , Diacetyl-dibenzoyl-morphine , 15-50 ,? 79 Tetrabenzoyl-morphine 14.13 ,, 9 99 In the same way the product of the action of acetic anhydride on tetrabenzoyl morphine was converted into the free base ; the ethereal solution of this however did not crystallise spontaneously; it was therefore converted into hydrochloride by treatment with warm dilute hydrochloric acid.Most of the base became converted into an almost insoluble tarry hydrochloride resembling in all respects tetrabenzoyl morphine hydrochloride ; a minute portion however dissolved. These two portions were converted into platinum salts and examined with the following results :-0.6800 gram of salt from insoluble hydrochloride gave 0.1015 Pt = 14.92 per cent. 0.0760 gram of salt from soluble hydrochloride gave 0.0110 Pt = 14.47 per cent. Tetrabenzoyl-morphine requires platinum = 14.13 per cent. I? Diacetyl-dibenzoyl-morphine , 15.50 , 9 7, Tetracetyl-morphine 17.17 , The physical characters of the resulting hydrochloride show that only a very minute amount of the readily soluble tetracetyl morphine or diacetyl-dibenzoyl-morphine hydrochlorides could have been present.Hence it may be concluded that there is no marked tendency towards the replacement of benzoyl by acetyl or vice zfersd on heating benzoylated morphine with acetic anhydride or acetylated morphine with benzoic anhydride. In conclusion we beg to tender our sincere thanks to Messrs. Mac-farlan and Co. (Edinburgh) for further supplies of pure alkaloids presented for the purpose of making these experiments.