Note: Descriptions are shown in the official language in which they were submitted.
1 ~ The present i.nvention relates to substitu~ed
quinolizidine ancl indolizidine derivatives haviny an-ticholineryic,
antihistamic, antitussive and analgetic activities, and to a
process fo~ producing the same, ~nd to therapeutie agents
eontaininy the same.
Atropine e~hibits strong antiacetylcholinergic activity ~.
and has been empLoyed as a spasmolytic agent for a long -time.
However, clinical use of atropine has been lim.ited because slde
eEfeets sueh as thirsty, dilation o-f the pupil, inerease in ;~
blood pressure are accompanied. Therefore, conventional
synthe-tie spasmolytic agents such as diphemanilme-thyl sulfa-te
(see, U.S.. Patent 2,739,969, Merek Index, 9th Edition, paye . : :
3309), priElnium bromide ~see, Merck Index, 9th Edition, page
7540), timepidiurn bromide (see, J. Med. Chem. ].5, 9].~(1972))
have been proposed and employed. These compounds, however,
are not satisfaetc)ry because strong antieholinergie main aetivity
is neeessarily aceompanied by strony side efEeets.
n object of the present invention is to.provide sa-tis-
~ fac-tory and perfeet therapeutic agents whieh have antieh.olinergie
activity as high as possible but side e:EEects as low a possibl.e.
It has been Eound that the substituted quinolizicline
ancl indolizi.cline deriva-tives haviny the Eoll.owincJ fo:rmula-
: ~ ~ A2 (I)
wherein Al and A2 are eaeh a phenyl.group or each a 2-thienyl group ~ld
n is an inteyer oE 3 or 4, and aeid addition salts thereof as
well as quartenary salts thereoE, exhibit strong anticholinergic
aetivity but have extremely low side efEects.
Another object of the present inven-tion is to provide
a proGess for produeing the derivatives represen-tecl hy the
, ~
.... ," . ..... ........
7~
`~ormula (I) and sal~s thereof which comprised clehydrating the
compounds repre~ented by ~he formula (
CH2) n ~
N ~ C
~" I \A2
OH (I~)
wherein A and A and n have the same ~eaninqs as cibove, optionally
foIlowed by reacting the resulting compounds with pharmaceutically
acceptable inorganic or organic acids or with quarternizing ;~
agents. Some of the raw materials represented by the formula
(II) are novel and some are ]cnown, which are prepared by con-
ventional methods, such as in accordance with the method
described in Chem. Ber. 90, pages 863-867 (1957).
The dehydration of the compounds represented by the
formula (II) is performed by heating at temperatures between
about 20 to about 150C, preferably 50 to 100C, more preferabl.y
at boil.ing points of solvents used, in a solvent in the presence
of a dehydrating agent. As solvents, a variety of solvents
such as water, methanol,~ethanol, benzené, toluene, etc. are
employed as far as they do not inhibit the dehydration. Typical
examples of dehydra-ting agents include hydrochloric ac.id,
sulfuric acid, phosp.horic oxychloride, p-toluenesul.foni.c acid,
~tc.
The thus obtained compounds represented by the formula
(I) can be converted into the corresponding acid addition salts
with pharmaceutically acceptable salts, such as hydrochloric
acid, hydrobromic acid, sulfuric acid, oxalic acid, maleic acid,
^ fumaric acid, citric acid, etc.
~ The quarternary salts of the compounds of the formula
(I) can be represented by the formula (III):
- 2 - :
)~ ' .
1/ ~= ;~
CN ~3 ~ ~ I I I )
wherein R is a lower alkyl group and X is an acid residue.
The quarternary salts can be prepared by reac-tiny the compounds
represented by the formula (I) wi-th the compounds represen-ted
by the formula (IV):
R - X (IV)
wherein R and X have the same meanings as defined above.
Specific examples of alkyl yroups for the R include
methyl, ethyl, propyl, butyll etc. Specific examples of
acld residues are a chlorine atom, a bromine atom, and a
iodine atom, a sulfuric acid residue, an alkyl sulfa-te residue,
and the like.
The aforementioned quarterniziny reaction can be performed
in the presence of or in the presence of solvents. Typical
examples of solvents to be employed are e-ther, acetone, alcohols
such as methanol or ethanol, etc. This reaction proceeds a-t
temperatures between 5 and 100C., preferably 10 and 40C.,
more preferably room temperature (ca. 20C), if necessary i.n
a sealed tube.
The quarternary salts of the formula (III) include
steric isomers (trans- and cis-isomers), and they can be
obtained as mixtures or pure isomers af-ter recrystallization.
Both isomers exhibit almost the same pharmacoloyical activities.
The compounds of the present invention represented by
the formula (I) and acid addition salts -thereof as well as
quarternary salts thereof exhibit s-trony spasmolytlc, anti-
histamic, antitussive and analyetic activities. In particular,
~ - 3 -
7~
l -the quartern~ry sa]ts have strorl~ anti-cholinergic and
anti-ulcer activi-ties but have reduced side effects such as
thirsty and dilation of the pupil.
The results of pharmacological tests with respect to
the compounds of the present invention are shown below.
Test Me-thod:
The ED50 values of these compounds relating to protective
activlty agains-t spasm induced by acetylcholine (lx 10 g/ml)
were measured using isolated ileum of guinea pigs according to
the Mag~us method, and relative potency was -thus examined,
taking the ED50 of atropine as lØ
Compounds: Relative Potency
2-DiphenylmethyLenequinolizidine methyl bromide 1.12
(Compound of Example 2 ii)
3-Diphenylmethylenequinolizidine methyl bromide 0.58
(Compound of Example ~ ii)
3-Diphenylmethylenequinolizidine ethyl bromide 0.45
(Compound of Example 4 iii)
2-(Dithien-2-ylmethylene) quinolizidine methyl 1.16
bromide (Compound of Example 10 i)
3-(Dithien-2-ylmethylene) quinolizidine methyl 0.86
bromide (Compound of Example 12 ii)
Atropine ]-
Scopolamin n-butyl bromide 0.02
Diphemanil methyl sulfate 0.11
~imepidium bromide 0.15
As can be seen Erom the results shown in -the table
above, the compounds of the present invention have far
stronger anti-cholinergic activity than scopolamine n-butylbromide,
diphemanil me-thyl sulfate or timepidium bromide.
In addition, the compounds of the present invention
have little side effects such as thirsty and dilation of the
~ - 4 -
g7''C~ '
l pupil, and thereEore are efEective as spasmolytic and anti-
ulcer ageilts ~or clin:ical use as compared -to atropin. Upon
clinical use -thereof, these compounds are employed in a dosage
of l to lO0 mg., preferably 3 to 30 mg., and administered three
times a day orally; or, can be parenterally administered in
the corresponding dosage.
~ he present invention will be explained hereaf-ter in
more detail with reference to the examples below.
_xample l
2-Diphenylmethylenequinolizidirle Hydrochloride:
To 1.39 y. of~,~diphenylquinolizidine-2-methanol was
added lO ml. of ethanolic hydrochloride. The resulting mixture
was refluxed for 4 hrs. with stlrring. The residue remained
after the removal of the et~hanol by distillation was dissolved
in water. The solution was rendered alkaline with a potassium
carbonate solution and extracted with chloroform. The chloro-
form layer was washed with water and dried. A-E-ter -the solvent
was removed by dlstil~lation, light yellow liquid was obtained.
The product was converted into the hydrochloride in a
.
~ conventional manner. By recrystallization from acetone-e-ther,
0.47 g~ of colourless needle 2-diphenylmethylenequinolizidine
hydrochloride showing a melt.ing point of 233-235C was obtained.
Elemental Analysis: C22H25N-HCl
calcd. C, 77.74; H, 7.71; N, 4.12
found C, 77.48; ~I, 7.59; N, 3.78
Example 2
i) 2-(Diphenylmethylene)quinolizidine Methyl Iodide:
In lO ml. of acetone was dissolved 0.1 g. of
~ 2-diphenylmethylenequinolizidine. After l.0 ml. o~f methyl
iodide was added to the resulting solution, the mi~ture w~s
-- 5
97C~
~ .
1 stirred for 24 hrs. at room tempera-ture. The crystals
precipitated were taken out by fil-tration. By recrystallization
from methanol, 0.1 g. of colourless needles showing a meltlng
point of 280-282C. (decompd.) were obtained.
Elemental Analysis: C23H28NI
calcd. C, 62.03; H, 6.34; N, 3.14
Eound C, 61.97; ~I, 6.43; N, 3.13
~ii) 2-(Diphenylmethylene)quinolizidine Methyl ~romide:
a) In 50 ml. of acetone was dissolved 5.5 g. of
2-diphenylmethylenequinolizidine. After 5 ml. of me-thyl bromide
was added to the solut1on, the mixture was allowed to stand for
48 hrs. at room temperature in a sealed tube. After the
completion of the reaction, the residue obtalned'by removing
'the solvent by dis-ti]lation~ was recrystallized from methanol-
acetone to obtaln 5.34 g. of colourless prism crystals showing
a melting point of 261-263~C. (decompd.).
NMR (CDC13) ~ - 3.33 (~ -CH3)
Elemental Analysis: C23H28N~r
calcd. C, 69.34; H, 7.08; N, 3.52 ,~
;20 ~ found C,~ 69.08; ~l, 7.16; N, 3.26
b) llhe residue obtained by distilling the thus obtained
mother'liquor of -the recrystallization above to dryness under
reduced pressure was recrystallized rom methanol-acetone, which
procedure was repeated twice -to obtain the mother liquors.
The combined mother liquors were distilled to dryness under
reduced pressure. The resul-ting resldue was recrystallized
' from methanol-acetone to give 1.12 g. of colourless prism
crystals showing a melting point of 235-236C.
NMR (CDC13) ~ : '3.67 (N -CH3)
~30
3~ 93t7a~
" ~ .
l iii) 2-(D_ henylmethylene)quinolizidine Ethyl Bromide: ;
This compound was prepared in a manner similar to the -
above.
Melting point: 233-234C. (from acetone)
Elemental Analysis: C24H30NBr ~;
calcd. C, 69.90; H, 7.33; N, 3.40
fo~md C, 69.58; H, 7.42; N, 3.26
Example 3
3-Diphenylmethylenequinolizidine:
a~ In 20 ml. of 60% sulfuric acid was heated 1.5 g. of
~ ,a -diphenylquinolizidine-3-methanol at 90 to 95C. for ~ -
30 mins. with stirring. After the completion of the reaction,
the reaction product was poured into water. The resulting
solution was rendered alkaline with a 10% aq. sodium hydroxide ~ !
solution and then extracted with ether. The ethereal layer
was washed with water and dried. The residue obtained after
removing the solvent by distillation was recrystallized from
hexane to obtain 1.1 g. of colourless needles showing a melting
point of 118 to 120C.
Elemental Analysis: C22H25N
calcd. C, 87.08; H, 8.30; N, 4.62
found C, 87.30; H, 8.33; N, 4.48
In accordance with a conventional manner, the product
was converted into the hydrochloride in a conventional manner.
By recrystallization from methanol, colourless plate-like
crystals having a melting point of 225 to 228C. were obtained.
b) ~ Diphenylquinolizidine-3-methanol employed as a
starting material was prepared in accordance with the following
method:
~;~ 30 To a solution of phenyl lithium, which had been prepared
_ 7 _
7(~
l by -the reaction oE 1.23 g. of lithium and 16.80 g. oE bromo~
benzene, in 50 ml. of absolu-te ether was dropwise added a
solution of 120 g. of 3-benzoylquinolizidine in absolute
ether. The mix~ure was refluxed for 30 mins. with stirring.
After -the excess of phenyl lithium was decomposed with water,
the reaction mixture was extracted with ether. The thus
obtained ethereal layer was washed with water and dried.
After removing the solvent by distillation, ~ diphenyl-
quinolizidine-3-methanol showing a melting point oE 166 to
lO 167C. was obtained.
Example 4
i) 3-Diphenylmethylenequinolizidine Methyl Iodide:
This compound was prepared in a manner similar to
Example 2 i) except that methanol was employed as the
, :
reaction solvent, and the residue obtalned aEter remov:ing
the solvent by distillation was recrystallized from me-thanol-
acetone.
Melting poin-t: 221-224C. ~colourless prisms)
lemental AnalySiS: C23H28NI
~ C H N
calcd. 62.03 6.34 3.14
found 61.94 6.34 3~00
ii) 3-Diphenylmethylenequinolizidine Methyl Bromide:
a) This compound was prepared in a manner similar to
:
Example 2 ii) a)~.
; Melting point: 259-261C. (decompd., colourless needles)
- NMR (CDC13) ~ : 2-97 (N~ -CH3)
Elemental Analysis: C23H28N3r
.
~30
- 8 -
7C~ ,
1 C H N
calcd. 69.34 7.08 3.52
found 69.60 7.29 3.26
b) In a manner similar to Example 2 ii) b), an isomer
of the so obtained methyl bromide was prepared from the mother
liquor of the recrystallization in accordance with similar
procedures to Example 2 ii) b).
Colourless crystals having a melting point of 256 to
259C. tfrom methanol-ether)
NMR (~DC13) ~ : 3.40 (N~ -CH3) -~
Elemental Analysiso C23H28NBr -
C H N
calcd. 69.34 7.08 3.52
found 69.06 7.20 3.48 ,~
iii) 3 Diphenylmethylenequinoliz1dine Ethyl Bromide:
This compound was prepared in a manner similar to
Example 2 ii) a).
Melting point: 225-228C (from acetone)
Elemental Analysis: C24H30NBr
C H N
calcd. 69.90 7.33 3.40
found 69.87 7.36 3.27
Example 5
l-Diphenylmethylenequinolizidine Sulfate:
3.5 g. of ~ Diphenylmethylenequinolizidine-l- ~ ;~
methanol was heated together with 35 ml. of 60% sulfuric acid
at about 100C. for 20 mins. The reaction mixture was poured
into water. After the mixture was rendered alkaline with a
20% aq. sodium hydroxide, the mixture was extracted with ether.
The ethereal layer was washed with water and dried. Ilhe residue
7a~
1 ~3.1 g) obtained after removing the solvent by distillation
was treated with ethanolic sulfuric acid. By recrystallization
of the thus obtained sulfate from ethanol, colourless needle
crystals having a melting point of 219 to 221C. were
obtained.
Elemental Analysis: C22H25N.H2SO4
C H N
calcd. 65.81 6.78 3.49
found 65.78 6.92 3.24
Example 6
_ _ :
i) l-Diphenylmethylenequinoliæidine Methyl Iodide:
In 20 ml. of acetone was dissolved 0.5 g. of l-diphenyl~
methylenequinolizidine. After 1.0 ml. of methyl iodide was
added to the solution, the mixture was allowed to stand for
10 mins. The crystals precipitated were taken out by filtration.
sy recrystallization of the obtained crystals (0.53 g.) from
methanol, colourless plate-like crystals having a melting point
of 294 to 296C (decompd.) were obtained.
Elemental Analysis: C23H28NI
C H N
calcd. 62.03 6.34 3.14
found 61.92 6.41 2.82
ii) l-Diphenylme ~ lenequinolizidine Methyl Bromide:
This compound was prepared in accordance with the
procedures similar to i) above.
Melting point: > 300C (from ethanol)
NMR (CDC13 ~ 3.19 (N~--C~3)
Elemental Analysis: C23H2gNBr
- 10 -
' ~
7~ ~ ~
1 ~ C H N
calcd. 69.34 7.08 3.52 ~;
found 69.29 7.19 3.27
iii) l-Diphenylmethylenequinolizidine Ethyl Bromide:
This compound was prepared in a manner similar to i)
above.
Melting point: ~ 300C. (from ethanol)
Elemental Analysis: C24H30NBr / 2
C H N
calcd. 68.40 7.41 3.32
found 68.61 7.313.24
Example 7
l-(Dithien-2-ylmethylene)quinolizidine Hydrochloride:~ ;
To 1.40 g. of ~,~-(dithen-2-yl)quinolizidine-1-methanol
was added 15 ml. of ethanolic hydrochloric acid. The mixture ; ;
was stirred for 1 hr. at 60C. The residue obtained by ~-
removing the solvent by distillation was dissolved in water.
The solution was rendered alkaline with a 10~ aq. sodium
hydroxide and then extracted with ether. The ethereal layer
was washed with water and dried. After removing the solvent
by distillation, 1.29 g. of light brown liquid was obtained.
; In accordance with a conventional method, the product was
converted into the hydrochloride. By recrystallization from ~ ~
isopropanol-isopropyl ether, the desired light brown prism 'r
hydrochloride showing a melting point of 194 to 197C. was
obtained. ~;
- ~lemental Analysis: C18H21NS2 .HCl
C H N
; calcd. 61.43 6.30 3.98
found 61.13 6.64 3.84
1~ - 11 -
, ... .. .
1 Example 8
1) 1-(Dithien-2-ylmeth_lene)quillolizidine Methyl Iodide:
I'his compound was prepared in good yield in a manner
similar to`Example 6 i) except that anhydrous acetone was ~
employed as a reaction solvent. ~ ~-
Light brown needles having a melting point of
284 to 285C. ~decompd., from isopropanol)
Elemental Analysis: ClgH24INS2
C H N
calcd. 49.89 5.29 3.06
found 50.02 5.48 2.99
In an analogous manner, the following compounds were
prepared:
ii) l~(Dithien-2-ylmethylene)quinolizidine Methyl Bromide:
Melting point: 294-297C. (from ethanol-isopropyl
ether, decompd.)
MNR (CDC13) g : 3.36 (N+ -CH~)
Elemental AnalysiS: ClgH24Br NS2
C H N
calcd. 55.60 5.89 3.41
found 55.18 6.11 3.51
(Dithie ~ ethylene)quinolizidine Ethyl Bromide:
Melting point: 286-288C. (from ethanol-isopropyl
ether, decompd.)
Elemental An,alysis: C20H26BrNs2
C H N
:
calcd. 56.59 6.17 3.30
found 56.79 6.54 3.13
Example 9
2-(Dithien-2-ylmethylene)quinolizidine:
- 12 -
1 This compound was prepared from ~ (dithien-2-yl)-
quinolizidine-2-methanol in a manner similar to Example 7
except that potassium hydroxide was used in place of sodium ~ '^
hydroxide and chloroform was used for the extraction in place
of ether.
Colourless crystals having a melting point of 88 to
90C. (from isopropyl ether)
Elemental Analysis: C18H21NS2
C H N ;
calcd. 68.53 6.71 4.44
found 68.34 6.72 4.26
Example 10
i) 2-(Dithien-2-ylmethylene)quinolizidine Methyl Bromide:
In a manner similar to Example 2 i), the following
compound was prepared.
Colourless crystals having a melting point of 246 to
248C. (from ethanol, decompd.)
NMR (CDC13) ~ : 3.42 (N - CH3)
Elemental Analysis: ClgH24Br NS2
C H N
calcd. 55.60 5.89 3.41
found 55.31 5.88 3. ln
ii) 2-(Dithien-2-ylmet_ylene)quinolizidine Ethyl Bromide: ~ ;
This compound was prepared in a manner similar to
Example 2 ii) a) except that the reaction mixture was heated
to 50C.
Colourless crystals having a melting point of 217 to
218C. (from isopropanol)
Elemental Analysis: C20H26Br NS2
- 13 -
7~
1 C H N
calcd. 56.59 6.17 3.30
found 56.30 6.15 3.31
Example 11
3-(Dithien-2-ylmethylene)quinolizidine:
This compound was prepared in a manner similar to
Example 7.
Colourless needles having a melting point of 128 to
130C. (from isopropyl ether)
Elemental Analysis: C18H21NS2
C H N
calcd. 68.53 6.71 4.44
found 68.35 6.74 4.36
Example 12
In a manner similar to Example 6 i), the ollowing
compounds were prepared:
i) 3-(Dithien-2-ylmethylene)quinolizidine Methyl Iodide:
Melting point: 223 to 224C (from ethanol)
Elemental Analysis: 19 24 2
C H N
calcd. 49.89 5.29 3.06
ound 49.66 5.35 2.72
ii) 3 (Dithien-2-ylmethylene)quinoliæidine Methyl Bromide:
Melting point: 278 to 280C. (from ethanol: decompd.)
NMR (CDC13) ~ : 2.92 (N - CH3)
Elemental Analysis: ClgH24BrNS2
C H N ;
calcd. 55.60 5.89 3.41
found 55.78 5.89 3.37
- 14 -
,~
9'7~
. iii) 3-(Dithien-2-ylmethylene)~uinolizidine Ethyl Bromide:
Melting point: 226 to 22~C~ (from isopropanol-
acetone; decompd.)
Elemental Analysis: C20H26BrNS2- 1/5 H2O
C
calcd. 56.12 6.22 3.27
found 56.13 6.18 3.G8
Example 13
l-Diphenylmethyleneindolizidine:
-
This compound was prepared from ~,~-diphenylindolizidine-
1-methanol in a manner similar to Example 5. ;;
Yellow viscous substance
Mass spectrum (C21H23N) : m/e: 289 (M ), 212
-Diphenylindolizidine-l-methanol employed as a
starting material was prepared as follows:
To a phenyl lithium solution prepared by dissolving
0.51 g. of metallic llthium and 6.32 y. of bromobenzene in
; 50 ml. of absolute ether, was dropwise added a solution of
2.40 g. of l-ethoxycarbonylindolizidine in 20 ml. of absolute ;~
ether under ice cooling. After refluxing for about 10 mins.,
water was dropwise added thereto, followed by extrackion with
ether. The ethereal layer was further extracted with dil.
hydrochloric acid. The aqueous layer was rendered alkaline
with an aq. sodium hydroxide solution and then extracted with
ether. The ethereal layer was washed with water and dried.
After removiny the solvenk by distillation, 3.5~ g. of light
yellow viscous substance was obtained.
Mass spectrum (C21~25NO)
m/e : 307 (M ~), 230, 123 ~basic peak)
The product was a mixture of two diastereoisomers and
1 used for the reac-tion above as i-t was.
e 14
In a manner similar to Example 6 i), the following
compounds were prepared:
i) l-Diphenylmethyleneindolizidine Methyl Bromide:
Colourless, plate-like crystals having a melting ~ -
poin~ of 210 to 211C. (from ethanol-acetone)
NMR (CDCl3) ~ : 3-49 (N ~ - CH3)
Elemental Analysis: C22H26NBr ~;
C H N `
calcd. 68.75 6.82 3.64
found 68.56 6.85 3.51
ii) l-Diphenylmethyleneindolizidine Methyl Iodide:
Melting point: 189 to 190C. (colourless needles)
iii) l-Diphenylmethyleneindolizidine Ethyl Bromide:
Melting point: 163 to 164C. (colourless plate-like
crystals)
Example 15
2-Dlphenylmethyleneindolizidine:
This compouna was prepared in a manner similar to
Example 5.
Melting point: 76 to 79C. (from n-hexane, colourless
needles)
Elemental Analysis: C21H23N
C H N
calcd. 87.15 8.014.84
found 87.08 8.144.76
Example 16
ln a manner similar to Example 6 i), the following
compounds were prepared:
- 16 -
9~ :
i i) 2-Diphenylmethyleneindolizidine Methyl Iodide:
Melting point: 242 to 244C. (from methanol-acetone,
colourless needles)
Elemental Analysis: C22H26NI
C H N
calcd. 61.26 6.08 3.25
found 61.00 6.15 3.13
ii) 2-Diphenylmethyleneindolizidine Methyl Bromide~
::
Melting point: 267 to 269C. (from methanol-acetone,
decompd.)
NMR (CDC13)~ : 3-08 (M~ -CH3)
Elemental Analysis: C22H26~Br
C H M
calcd. 68~75 6.82 3.64
found 68.57 6.82 3.53
~Example 17 -
2-(Dithien-2-ylmethylene)indolizidine:
To 2.66 g. of ~ (dithien-2-yl)indolizidine-2-methanol
was added 20 ml. of ethanolic hydrochloric acid. The mixture
was st1rred for 1.5 hrs. with heating at 60C. Water was
.
added to the resldue obtained ater removing ethanol by
,
distillation to dissolve. Thereafter, the solution was
rendered alkaline with a 10% aq. sodium hydroxide solution and
then extracted with ether. The ethereal layer was washed with
water and dried. The residue remained after removing the
solvent by distillation was distilled -to obtain 1.76 g. of
~ .
yellow liquid showing a boiling point of 195 to 197C. (3mmHg).
In accordance with a conven-tional manner, the product was
converted into the hydrochloride. By recrystallization from
3 isopropanol, yellow prisms having a melting point of 197 to
- 17 -
7~
., :
1 200C. (decompd.) were obtained.
Elemental Analysis: C17lll9NS2 . HCl
C H N
calcd. 60.42 5.97 4.14
found 60.17 6.12 3.87
Example 18
In a manner similar to E~ample 2, the following compounds
were prepared:
) 2-(Dithien-2 ylmethylene)indolizidine Methyl Iodide:
Meltlng point: 222 to 225C. (from isopropanol, colourless ;~
to llght brown prlsms)
Elemental AnalyslS: Cl8H22INS2
C H N
calcd. 48.76 5.00 3.16
found 48.60 5.04 2.85
il) 2-(Dithien~2-ylm thylene)indolizldine Methyl Bromlde:
Melting point: 200 to 202C. (from isopropanol)
~ NMR (CDCl3) ~ : 3-49 (N~ -CH3)
`~ Elemental Analysis: C]8H22BrNS2 1/5 H20
C H N
calcd. 54.05 5.64 3.50
found 54.02 5.59 3.24
iii) 2-(Dithien-2-ylmethylene)indolizidine Et_yl Bromide:
Melting point: 212 to 214C. (from isopropanol-acetone)
l AnalySiS: ClgH24BrNS2
C H N
calcd. 55.60 5.89 3.41
found 55.33 5.91 3.16
- 18 ~
