THE ALKALOIDS OF ROLARRRENA CONGOLENSIS STAPF. 163 XV 111.- The Alkaloids of Holarrhena congolensis, Stapf By FRANK L’EE PYMAN. FRBRE JUST. GILLET S.J. a missionary in the Belgian Congo, reported some years ago that on chewing the leaves of Hdacrrhem congolensis Stapf a local anaesthetic effect was produced on the mucous membrane of the mouth. This led the author t o examine the alkaloids of the plant in 1913 when a new base termed holarrhenifie @2AH380N2 was isolated together with the alkaloid conessine which has been obtained previously by several authors from other species of Holarrhena. The physiological action of conessine and holarrhenine was studied by J. H. Burn ( J . Yharmacol, 1915 6 305) who found that whilst they had a local anEsthetic action this property was of no practical value since they produced local necrosis when injected subcutaneously.Since it is improbable that the author will continue this investi-gation it is desired to put on record the properties of holarrhenine and also the results of a few experiments on conessine carried out a t that time. These are for the most part in agreement with the recent work of Giemsa and Halberkann (Arch. Pharm,. 1918 256, 201)) and confirm the formula C,4H40N supported by these authors, not that--CBH3,N2-put forward by Ulrici (Arch. Pluwm. 1918, 256 57). Giemsa and Halberkann’s view that conessine contains two dialkylamino-groups is not shared by the present author who found conessine to contain only three alkyl groups (no doubt methyl groups) attached to the nitrogen atom.Moreover Polstmff and Schirmer (Ber. 1856 19 84) showed that conessine dimetho-hydroxide yields on heating a crystalline base together with ‘‘ ammonia ” (doubtless trimethylamine). It is therefore probable that conessine contains an iV-methyl group forming a link in a heterocyclic ring to which a side-chain bearing a dimethylamino-group is attached. Holarrhenine resembles conessine in containing three N-alkyl groups. It yields a momoacetyl derivative, C%H4,,O2N9 which is diacidic whence it follows that holarrhenine contains a hydroxyl group. EXPERIMENTAL. Isolation of the Alkaloids. Twenty-nine kilograms of the bark of the trunk of Holarrhena congdensis Stapf were percolated with very dilute hydrochlori 164 P Y U N ALfiEBxIoIDS OF HOLARREENA OONWLF;NSIS STBPF.acid. The liquor was made alkaline With ammonia and extracted with chloroform. After distillation of the solvent the dark, viscous residue was extracted first with light petroleum and then with ether. The light petroleum extract was shaken with dilute hydrochloric acid the base regenerated with sodium carbonate and extracted wit'h light petroleum. The extract was distilled and the residue dissolved in a solution of 0.7 part of hydrated oxalic acid in 4 parts (by weight) of alcohol. On keeping a cdourless crystal-line hydrogen oxalate (m. p. 249O) separated in a yield amounting to 0.9 per cent. of the bark. The oxalate was dissolved in water, the base regenerated by sodium carbonate and extracted with light petroleum. After distilling the extract the residue was dis-solved in a little acetone and kept when conessine separated in colourless plates amounting t o 0.25 per cent.of t h e bark. A further quantity was obtained by working up the mother liquor. The ethereal extract of the total alkaloids was extracted with dilute hydrochlorio acid and this was basified with ammonia and extracted first with light petroleum and then with ether. The light petroleurn extract was worked up as before for conessine. The ethereal extract was concentrated and left for some time when a small quantity of holarrhenine crystallised out. Conessiw . The base employed in this investigation was purified by crystal-lisation from acetone which is particularly suitable for the purpose, as Giemsa and Halberkann have remarked.The base is only sparingly soluble in cold acetone but dissolves in boiling acetone to the extent of approximately 10 per cent. On cooling it separates in large colourless plates which apparently contain acetone of crystallisation for they effloresce quickly in the air, becoming free from solvent. Found C = 81'0 80.7 ; H = 11.3 11'4 ; N = 7.9 ; Me(attached to C,,H,,N requires C = 80.8 ; I3 = 11.3 ; N = 7.9 ; Me(attached to N) = 12.6 per cent. The molecular weight was determined by the cryoscopic method 0.2330 in 29.92 benzene gave A t = -O*10Bo. The base melted a t 125O (con.). N) = 12'5 13.0. in benzene: M.W. =361. 0-4442 , 29.92 , ,) A t = -0.213'. M.W. =349. CZ4Hk0N2 requires M.W. =356*5. The specific rotatory power of the base was determined in chloro-form solution PYMAN ALLOIDS OF HOLARRHIHA CONGOLENSIS.STAPF. 165 The specific rotatory pw0r of a specimen of the hydrobromide (containing 2.4 per cent. of water) was determined in aqueous solution : %+0.56O; c=3*858; 15.2 dcm.; [a],,+7*4O for the anhydrous salt. Conessin4e hydrogtn oxalate forms prisms readily soluble in hat, but rather sparingly so in cold water and sparingly soluble in alcohol. It melts and decomposes at 280' (corr,) and is anhydrous. Found C = 62.5 ; H = 8.1, C24H40Nz,2C,H,04 (536.5) requires C = 62.6 ; H = 8.3 per cent. Hdarrhenine C,,H,ON,. The crude base was first purified by crystallisation from ethyl acetate when it melted a t 190° and then converted into the hydro-bromide. This salt was crystallised from water and washed with acetone.It was then reconverted into the base and this was recrystallised from ethyl acetate when it separated in silky needles which melted at 197-198O (oorr.). It is insoluble in water readily soluble in alcohol or chloroform but sparingly so in cold ethyl acetate acetone or ether. Found C=77*5 77.6 77.3; H=10*2 10.3 10.7; N=7.7; It suffers no loss a t looo. Me(attached to N ) = l l * l 12'2. C,H,ON (37004) requires C = 77.8 ; H = 10.3 ; N =7*6 Me(attached t o N)=12.2 per cent'. The specific rotatory power was determined in chloroform solution : % - 0.75' ; ~ ~ 5 . 2 4 8 ; 1=2 dm.; [~],-7*1O. The kyhobrumide cryshllises from water in flat needles which It is readily soluble in The air-dried salt con-melt at 265-268O (corr.) after drying.hot somewhat sparingly so in cold water. tains 3H20 (Found H20 =9*0. Calc. H20 = 9.2 per cent.). Found in salt dried at looo C=54.4; H=8.2; Br=29*8. C,HB0N,,2HBr (532.3) requires C=54.1; H =7.6; Br=30*0 per cent. The specific rotatory power was determined in aqueous solution: %+1*02O; c=4*630; Z=2 dcm.; [a],+ll*OO or +12-lc for the anhydrous salt. -4 cetylhoZarrhenine prepared by the action of acetic anhydride and anhydrous sodium acetate on holarrhenine crystallises f porn e&ne in large colotirlws oblong plateg which melt a t 180° (con.). VOL. OXVr 166 PYMAN META-SUBSTITUTED It is insoluble in water sparingly soluble in cold alcohol acetone, or ether but readily so in chloroform. Found C=75-7; H=9*9; N=6.8. Equivalent to HC1 using methyl-orange = 202. C28H100$T2 (412.5) requires C =75*7 ; H= 9-8 ; N = 6.8 per cent. [Received Pebruury 4th 1919.1 THIE WELLUOME ~ ~ ~ P M I C A L WORKS. D~TBORD KENT