204 
THE PHARMACEUTICAL JOURNAL AND TRANSACTIONS. 
[September 14, 1872. 
= c = c 36 h 42 n 2 o. 
Go _ C 7 oH 84 N 4 0 ]2 
Codeine 
Dicodeine 
Tricodeine = C 3 = C; w H m N 0 O ls 
Tetracodeine = C 4 = C 144 H I 6 s N 8 0 24 
Morphine = M = C s 4 H 38 N 2 O s 
Dimorphine = M„ = C m H„N 4 O u 
Trimorphine = M 3 = C 102 H 1 ] 4 N 6 O l3 
Tetramorphine = M 4 = C, 36 H 152 N 8 0 24 
^ Each of these bases is apparently capable of giving 
rise to a large number of derivatives. In the codeine 
senes both the polymerides themselves and many ol 
their derivatives have been obtained. In the morphine 
senes, the polymerides themselves have not been formed 
as yet; nor have the derivatives of trimorphine been 
obtained with, certainty; but derivatives of tetramor- 
phine and dimorphine have been obtained, some being 
formed by the removal of the elements of water Rom 
the polymerides themselves; the dehydro- or “apo-” 
derivative of the latter polymeride is apparently the 
apomorphine examined some few years ago by the late 
Dr. A. Matthiessen and the author. 
When hydriodic acid and phosphorus act on codeine, 
methyl is eliminated as iodide and a series of substances 
form j ma ^ e ’ which are expressible by the general 
(i\I 4 -f II 16 ) -f- nHI + p H 2 0 
Py Pushing the treatment further, other substances 
are formed having- the general formula— 
(i\I 4 -f- II lt5 — 0 8 ) -j- nHI + p H 2 0. 
"\\hen morphine is subjected to the same treatment, 
products are formed which are apparently absolutely 
ldentica! with the. corresponding codeine products. 
Much fewer derivatives are, however, obtainable from 
morphine, the fact of their being no methyl to eliminate 
and thus place the substance in a quasi-nascent state, 
being probably the reason for this difference. Thus the 
morphine derivatives hitherto obtained all belong to 
the first series— ° 
(M 4 -f H 16 ) -f- nHI + p H 2 0, 
none of the other series cc ntaining less oxygen having 
been obtained as yet from this base. These derivatives 
ha\e no marked physiological action, considerable doses 
( U P to eight grains) being- given to an adult she-terrier 
without producing any result other than a purging 
action lasting for a few hours. ° 
It is noteworthy that both from morphine and codeine 
the sme compound (M 4 + H 10 ) + OHI - 4H„0 isderi- 
vable. . I he formula of this substance (C m H lfi 1 IN a Oo„ 
tlf?Ilf ^ Ca b able of bei T? halved, and indicates that 
t e iodized bases are really C 136 compounds, and not 
C 68 , as was supposed at first. On account of the simi¬ 
larity in physical properties between these iodized 
derivatives and the bromotetracodeine, chlorotetramor- 
phme, etc. obtained by the action of hydrobromic acid 
on codeine the formulae of these latter substances are 
be d ° uble of those for merly attributed 
and nSV L o y i ai l VieWad aS C i36 - C J44 compounds 
stifl oou bfr, , C ^ bodie3 - Inasmuch, however, as they 
still contain four times as much carbon as the codeine 
exulaTneu Tho (theSG tW ° are ' doubled as above 
clafs of bodS °v T StlU appifoable; and this 
class of bodies, which are characterized, by the property 
of being- amorphous and insoluble in (ther may be 
conveniently alluded to as the “ tetra bases .” } 
out alterations b of codeine themselves with- 
-! COndar y tactions, the action 
o ac els other than hydracids was examined. Phosphoric 
Tueous TolSn f° ^°- Ut 2 - 00 ° (by boiIta S d0 ™ the 
aqueous solution of codeine m excess of glacial nhos 
phone acid) yields Mine soluble in ether aSorphous 
but forming crystalline salts, and fcftSJKE*mu4 
resembling in its properties all the other “ tetra bases” 
examined, being insoluble in ether and amorphous, 
and forming amorphous salts. These two bases appear 
to be identical respectively with the “ isomer of codeine” 
of Armstrong, and the “ amorphous codeine ” of Ander¬ 
son, both prepared by the action of sulphuric acid on 
codeine. On examining this reaction, a third poly¬ 
meride was also found to be formed, which is amorphous 
and soluble in ether, but which forms amorphous salts. 
On account of this body being in many properties and 
respects . intermediate between dicodeine and tetra¬ 
codeine, it is considered to be tricodeine. 
The proof of the correctness of the formula! attributed 
to dicodeine and tetracodeine is as follows: when di¬ 
codeine is. treated with hydrochloric acid it undergoes 
the following reaction:— 
C 72 H S4 N 4°]2,4HC1+HC1=H 2 0 -f C r 2 II 83 Cl N 4 O u ,4HC1. 
The resulting body is soluble in ether and gives amor¬ 
phous salts, whereas dicodeine hydrochloride is crystalline. 
Hence this body is not a tetra base, and hence the in¬ 
ference is that dicodeine has a C 72 formula. When 
codeine itself is similarly treated, the first product of the 
reaction contains chlorine and carbon in the ratio 1 to 
36, whence codeine is a C 36 body. Tetracodeine evi¬ 
dently belongs to the same general group as the sub¬ 
stances termed “tetra bases;” and as these have been shown 
to be C 144 compounds, it follows that tetracodeine has 
double the formula of dicodeine, which again is double 
that. of codeine: whence the names. Tricodeine is 
considered to be such on account of its properties, which 
are intermediate between those of dicodeine and tetra- 
codeiue; the action of sulphuric acid on dicodeine does 
not give rise to tricodeine, but does to tetracodeine, so 
that tricodeine is formed directly from codeine. The 
action of hydrochloric acid on tricodeine is, however, 
quite different from that on codeine and dicodeine ; the 
elements of water are removed, and the product contains 
no chlorine at all. Tetracodeine, on the other hand, 
undergoes no change when heated for a long time with 
hydrochloric acid. 
The action of hydriodic acid on codeine, dicodeine and 
tetracodeine is again. very different, as exemplified in 
the following reactions :— 
Codeine 4C + 36HI = SCH 3 I + 4H 2 0 + I 16 + 
(1M 4 + H^+ 12HI - 4H,0). 
Dicodeine 2C 2 + 25HI = 8 CH 3 I + 4H.,0 + I s + 
(M 4 + H 8 + 9HI - 411,0). 
Tetracodeine C 4 + 18HI = 8 CH 3 I + 2H 2 0 + 
(M 4 + 10HI _ 2H 2 0). 
V ith the codeine H 16 is added on to M 4 ; with the dico- 
deine H 8 only ; and. with the tetracodeine no II at all; 
a tetra base results in each case. The product from di- 
codeine has the formula C 136 H 153 IN s O 20 , 8 HI, which con¬ 
tains C 136 and is. incapable of being halved. Sulphuric 
acid converts dicodeine into tetracodeine, no tricodeine 
being produced thereby ; hence tricodeine is a polymeride 
formed directly from codeine, and is not produced by the 
metamorphosis of dicodeine previously produced; the 
reverse being true for tetracodeine. 
Dr. Stocker finds a considerable difference in the 
physiological actions of these different polymerides ; the 
higher polymerides usually produce vomiting or diarrhoea 
(in cats and dogs), while codeine produces a peculiar 
hypersensitiveness and cerebral congestion not noticeable 
with the others. 
When morphine is treated with phosphoric acid, two 
products are obtained corresponding in properties to 
dicodeine and tetracodeine; these are not, however, 
the polymerides themselves, but are derivatives there¬ 
from derived by. abstraction of the elements of water. 
One is soluble in ether, and foims crystalline salts, 
though amorphous itself. This is produced only in 
small quantity, and appears to be identical with apo- 
