close

Вход

Забыли?

вход по аккаунту

?

Патент USA US3067229

код для вставки
it
fates
z
3,067,219
r
k
atent
Fatented Dec. 4, 1962
2
Ii
pared by a process illustrated by the following equations:
3,667,219
6-CHLOR0 DERIVATIVES 0F M-PREGNEN-Ua?l
DHOL-3,20-D1IONE AND AlA-PREGNADlENE-l’loc,
VZJL-DIGlL-E?tl-DEGNE
(IJHzOR
CHzOR
to
oo
I
VIE“
Howard J. Ringoid and Octavio Mancera, Mexico City,
Mexico, assignors, by mesne' assignments, to Syntex
Corporation, a‘ corporationyof Panama
No Drawing. Filed Aug. 29, 1958, Ser. No. 757,939
Claims priority, appiication Mexico Aug. 30, 1957
14 Qlaims. (6i. 26(i--397.47)
1O
The present invention relates to novel cyclopenta
nophenanthrene compounds.
More particularly the present invention relates to 6
or)
chloro derivatives of A4-pregnen-17a,21-diol-3,ZO-dione
"and A1'4-pregnadien-l7a,21-diol-3,20-dione, the 2l-esters 15
of these compounds of hydrocarbon carboxylic acids of
ethylene glycol
O
and epoxidation l: \
O
O,
ethyl
orthoformate
less than 12 carbon atoms, and the 17u,21-diesters of
dry H 01
acetic acid
(EH20 R
these compounds of hydrocarbon carboxylic acids of less
OHzO R
oo
than 12 carbon atoms. Within the foregoing de?nition
20
the 616-chloro compounds to be hereinafter set forth in
detail are intermediates for the production of the corre
sponding ?a-chloro compounds. The 6a-chloro com
pounds above set forth are intermediates for the produc
tion of the active cortical hormones, 6a-chloro cortisone 25
and hydrocortisone by well known methods involving the
microbiological introduction of an 11,8- or lla-hydroxy
_
A] :|— -OH
131mg 5
h0
0': g
‘ :L- OH
('31
group followed (for 6a-chloro cortisone) by oxidation
to an ll-keto group. In addition the 17a,21-diesters of
the 6a-chloro compounds above set forth are valuable 30
lhypochlorous
acid
progestational hormones.
In accordance with the present invention it has been
discovered that 5a,6a-epoxide derivatives of pregnanc
17a,21-diol-20-one having in the C—3 position a ketal or
alcohol group upon reaction with hydrogen chloride gave
a corresponding 6-chloro derivative. As will be herein
after set forth depending on reaction conditions these
@etic acid
(EH20 R
GO
/\\ l "OH
derivatives were either 6B-chloro or 606-011101'0 com
pounds.
The novel compounds of the present invention are il 40
lustrated in the following formulas:
C—Q‘j
o1
CHgOAc
45
‘
(llHioAo
o
oo
l :L-—O Rs‘
50
.0? m or)
,.
HO
peracid
-"
'
:'-'- o R2'
‘
..
HO
.
0i
55
H01
In the above formulas R represents hydrogen or‘ a‘
hydrocarbon carboxylic acid ester group of‘ less than 12
onions
or‘noAc
unsaturated, of straight or branched chain, cyclic or
(I30
IO
mixed cyclic-aliphatic, unsubstituted or substituted con
i~~0m
carbon atoms.
These ester groups may be saturated or 60
ventionally asv with methoxy or halogen‘. Examples‘ of
such ester groups include acetate, propionate, cyclopent
ylpropionate, benzoate, butyrate, etc. R1 represents hy 65
drogen or' a hydrocarbon carboxylic acid ester group of
les than 12 carbon atoms when R represents a hydro
carbon carboxylic acid ester group of less than 12 car
ehromio
O —‘
.
aci
'd
7 -
bon atoms and R1 represents hydrogen when R is hydro
gen. X represents a double bond between C—1 and ‘0-2 70
or a saturated linkage between C—1 and C—2.
The novel compounds of the present invention are pres
Al :- -OR:
/Y
.
HO
.
l
\/
HO
l
Cl
dry ‘n 01
acetic'aci'd
3,067,219
it
mild saponi?cation as by reaction with sodium methoxide
I
at a low temperature gave the corresponding free com
CHzOAC
.
CHzOR
to
to
A I --0 R2
’
230 R1
saponi?catlon
I
———----->
O:
l
O:
To
17a,21-diol-3,20-dione was reacted with a corresponding
acid anhydride in pyridine in a conventional manner. To
obtain the 17,21-diesters the same compound is reacted
prolonged period or under re?ux. The acid condition may
be produced by an excess of anhydride or by p-toluene
sulfonic acid for example. To form a 17,21-mixed di
i
ester the 2l-mono-esters are further esteri?ed with a differ
Cl
CH2O R
C1120 R
<50
to
ht‘
to“
Le I /
l
diesters having the same or different ester groups.
form the 21-monoesters the free 6a-chloro-A4-pregnen
10 under acid ‘conditions either at room temperature for a
reesteritication O
01
pound. The free compound was then reesteri?ed either to
form the 21-monoesters previously described or 17,21
dehydrogenation
O_
ent acid anhydride under conditions as set forth for 17,21
diester formation.
As indicated in the third equation above the 2l-mono
esters or 17,20-diesters of 6a-chloro-A4-pregnen-17a,21
diol-3,20-dione are dehydrogenated to the corresponding
Aid-compounds. For this reaction the preferred agent is
selenium dioxide in the presence of tertiary butanol and
pyridine. The‘same dehydrogenation may however be
performed by known microbiological methods. The esters
of 6tx-chloro-A1A-pregnadien-l7u,21-diol - 3,20 - dione are
In the above equations R and R1 represent the same
transformed to the free compound by conventional sapon
i?cation.
The following speci?c examples serve to illustrate the
groups as heretofore set forth. Ac represents acetate. Et
present invention but are not intended to limit the same.
a
$1
represents ethyl. R2 represents hydrogen or acetate.
Referring to the ?rst of the above equations Reichsteins
substance “S” Zl-acetate (A‘l-pregnen-17a,21-diol-3,20
dione 21-acetate) is conventionally converted as known
in the art to 3-ethylenedioxy-5a,6ot-oxido-pregnan-17a,21
diol-ZO-one 21-acetate or to the ZI-acetate of 3-ethoxy
Example I
5 g. of the 2l-acetate of 3-ethylenedioxy-5a,6a-oxido
pregnan-l7a,2l-diol-20-one was dissolved in 250 cc. of
glacial acetic acid and a slow stream of dry hydrogen chlo
ride was introduced into the solution, for a period of 2
A3'5-pregnadien-l7m21-diol-20-one, by reaction with eth 35 hours, maintaining the temperature of the mixture below
ylene glycol followed by epoxidation with a per acid, or
18° C. It was then poured into ice water and the reaction
by reaction with ethyl orthoformate. Reaction of the 21
product was extracted with methylene dichloride, washed
acetate of 3 - ethylenedioxy-Sa,6a-oxido-pregnan-1704,21
diol-ZO-one with dry HCl in acetic acid gave the 2l-ace
tate of 6a-chloro-A4-pregnan-17a,2l-diol-ZO-one. If an
other ester of substance S is used as the starting material
of the character set forth previously the ?nal product is
with 5% sodium carbonate solution and water to neutral,
dried over anhydrous sodium sulfate, ?ltered and evap
orated to dryness. Crystallization of the residue from
acetone-‘hexane afforded the 2l-acetate of 6zx-ChlO1'0-A4
ester of 3-ethoxy-A3'5-pregnadien-17a,21-dio1-20-0ne by
reacting these compounds with hypochlorous acid. The
pregnen-l7u,21-diol-3,20—dione with M.P. l85~l86° C.,
[u]D+99.5° (chloroform), A max., 238 my. (log E 4.17).
Example II
When in the previous example the 21-acetate of 3-ethy1
hypochlorous acid for the reaction is obtained in situ as
by treatment with n-chlorosuccinimide in acetone solu
substituted by the Zl-acetate of 3-propylenedioxy-5a,6a
tion in the presence of sodium acetate and acetic acid. In
oxido-pregnan-17oz,21-diol-20-one, there was also obtained
the corresponding ester.
As indicated the same com
pounds may also be prepared from the 21-acetate or other
enedioxy - 5:1,6ot - oxido-pregnene-l7a,2l-diol-20-one was
place of the n-chlorosuccinimide other N-chloro-imides or
the 2l-acetate of 6a-chloro-A4-pregnen-17a,21-diol-3,20
N-chloro-amides may be used such as N-chloroacetamide
or N-chloro-benzenesulfonamide. Alkali metal or alkaline
earth metal hypochlorites may also be used such as so
dione, identical to the ?nal compound ‘obtained by the
method of Example I.
dium or calcium hypochlorite. The compounds obtained
after this last step are the corersponding 21-esters of 618
Example III
A mixture of 2 g. of the 2l-acteate of 3-ethoxy-A3’5
pregnadien-l7a,21-diol-20-one, 40 cc. of acetone, 8 cc. of
pounds are then converted to the corresponding 6a-chloro
Water and 800 mg. of sodium acetate was cooled to 0° C.
compounds by treatment with dry HCl in acetic acid.
and treated with 800 mg. of N-chlorosuccinimide and then
In the second equation above the starting material is a
with 0.8 cc. of glacial acetic acid. The mixture was stirred
2l-acetate or a 17,2l-diacetate of A5-pregnen-3/8,17u,21 60 for 1 hour at 0° C. and then poured into water; the pre
triol-20-one. Treatment of these compounds with a per
cipitate was collected, dried and recrystallized from ether,
chloro-A4-pregnen-17a,21-diol - 3,20 - dione.
These com
acid such as m-onoperphthalic acid gave the corersponding
5a,6a-oxido compounds. Treatment of these oxido com
pounds With hydrogen chloride in chloroform gave the
corresponding acetates of 6/3-chloro~pregnan-35,5a,17a,
21-tetrol-20-one. Upon treating these tetrols with chromic
acid the 3B-hydroxy group was oxidized to a 3-keto group
to give the 21-acetate or 17,2l-diacetate of 6,8-chloro-preg
nan-5a,17a,21-triol-20-one. Treatment of these last com
pounds with dry hydrogen chloride in acetic acid dehy
drated the compounds and inverted the GB-chloro to 6m
chloro to, give the 2l-acetate or 17,21-diacetate of 6a
chloro-‘i-pregnen-l7a,2l-diol-3,20-dione. ‘Both these ace
tates and the 21-esters of 6zx-chloro-A4-pregnen-170:,21
thus yielding the crude 21-acetate of 6/3-chloro-A4-preg
nen-l7a,2l-diol-3,20-dione which was puri?ed by recrys
tallization from acetone-hexane; M.P. l93—l94° C., k
max. 240 mp, log E 4.15, [a]D+4.13° (chloroform).
Example IV
In the previous example N-chlorosuccinimide was sub
stituted by N-chloroacetamide with the same ?nal result.
Example V
In the methods of Examples III and IV, the 21-acetate
of 3-ethoxy-A3'5-pregnadien-l7a,2l-diol-20-one was sub
stituted by the 2l-acetate of 3~methoxy-A3-5-pregnadien
diol-3,20-dione, previously described, upon conventional 75 17a,21-diol-20-one with the same ?nal result.
3,067,219
5
%
Example VI
0° C. and then the mixture was diluted with water and
extracted‘ with ether. The extract was washed, dried over
1 g. of the 21-acetate of ?p-chloro-A‘l-pregnen-17a-21
diol-3,20-dione obtained by any of the methods of Exam
ples III to V, was [dissolved in 50 cc. of glacial acetic acid
ness. Recrystallization oi; the residue from acetone yield~
ed the 21-acetate of 6p-chloro-pregnan-5a,17a,21-triol
and a slow stream of dry hydrogen chloride was intro
3,20-dione.
duced into the solution for 2 hours maintaining the tem
perature below 18° C. The reaction product was worked
anhydrous sodium sulfate, ?ltered and evaporated to dry
2 g. of the 21-acet'ate of 6B-chloro-pregnan-5a,170:,21
triol-3,20-dione was dissolved in 80 cc. of glacial acetic
up as described in Example I. There was thus obtained
acid and a slow stream of dry hydrogen chloride was
the 21-acetate of 6a-chloro-A4-pregnen-l7a,2l-diol-3,20 10 passed into the solution for 2 hours at a temperature
dione, identical to that obtained in such example.
around 18° C. The mixture was diluted with water and
they product was extracted with ethyl acetate, washed with
water, 5% sodium carbonate solution and water, dried
A suspension of 1 g. of the Zl-acetate of 6a-chloro-A4
over anhydrous sodium sulfate and evaporated to dryness.
pregnen-17a-21-diol-3,20-dione in 10 cc. of absolute meth
Crystallization of the residue from acetone-hexane af
15
anol was cooled to 0° C. and mixed under nitrogen with
forded the 21-acetate of 6a-chloro-A4-pregnen-1~7a,21-diol
a cooled solution of sodium methoxide prepared by dis
3,20-dione, identical with the compound of Example I.
solving approximately 60 mg. of sodium in 5 cc. of abso
Example XI
lute methanol. The mixture was stirred under nitrogen
A suspension of 3 g. of the 21-acetate' of 5a,6a-oxido
for 1 hour and then poured into a cooled saturated aque
. Example VII
ous solution of sodium chloride containing 0.3 cc. of 20 pregnan-B?,17a,21-triol-20—onc in 200 cc. of acetone was
mixed with 10 cc. of concentrated hydrochloric acid and
glacial acetic acid. The precipitate was collected, washed
stirred for one and a half hours. It was then poured into
with water, dried and crystallized from acetone-hexane,
saturated aqueous sodium chloride solution and extracted
thus giving 6a-chloro-A4-pregnen-17a,21—diol-3,20-dione.
Example VIII
By the same method of the previous example, the 21
with three portions of methylene dichloride. The extract
25 was washed with 5% sodium carbonate solution and then
with water, dried over anhydrous sodium sulfate and con
acetates of 6,8-cliloro-A4-pregnen-17a,21-diol-3,20-dione
centrated to 30 cc. The mixture was cooled and the crys
was converted into the free 6?-chloro-A4-pregnen-l7a,21
talline precipitate was collected, thus giving the ZI-acetate
diol-3,20-dione.
of 6,8-chloro-pregnan-313,5a,17a,21-tetrol-20-one, identical
Example IX
A mixture of 1 g. of 6B-chloro-A4-pregnen-17u,21-diol
3,20-dione, 10 cc. of pyridine and 1 cc. of propionic an
hydride was kept overnight at room temperature and
with the compound obtained by the method of Example
X.
Example XII
3
g.
of
the
ZI-acetate
of
6a - chloro - pregnan
poured into water. The mixture was heated on the steam 35 3e,5a,17a,21-tetrol-20-one dissolved in 100 cc. of acetic
bath for half an hour, cooled and the precipitate was col
lected.
Recrystallization from acetone-hexane yielded
the 2l-propionate of 6B-chloro-A4-pregnen-l7a,21-diol
3,20-dione.
Similarly, there was prepared the 21-propionate of 6a
chloro-A4-pregnen-17a,21-diol-3,20-dione; When propi
onic anhydride was substituted by the anhydride or chlo
ride of another hydrocarbon‘ carboxylic acid, of up to 12
carbon atoms, there were obtained the corresponding 21
esters. Speci?cally there were obtained in this way the-21
cyclopentylpropionate and the 21-benzoate.
Example X
A solution of 5 g. of the 21-acetate of A5-pregnen
3?,17a,21-triol-20-one in 100 cc. of chloroform was mixed
acid was mixed with 950 mg. of chromic acid previously
dissolved in 20 cc. of 80% acetic acid. The reagent was
added dropwise to the stirred solution which was kept at
a temperature below 15° C. The stirring was continued
for
2 hours at 15° C. and the mixture was then diluted
40
with water and the precipitate formed was collected,
washed with water, dried and recrystallized from acetone
hexane, thus yielding the 21-acetate of 6B-chloro-pregnan
5a,17a,21-triol-3,20-dione, identical with the‘ compound
obtained by the method of Example X.
45
Example XIII
By the methods of Examples X to XII, the 17,21-di—
acetate of A5-pregnen-3?,17a,21-triol-204one was con
with 1.5 molar equivalents of monoperphthalic acid in
verted into the 17,2l-diacetate of 5u,6a-oxido-pregnan
3a,17a,21-triol-20-one, then into the 17,21-diacetate' of
ether solution and the mixture was kept at room tempera
ture for 20 hours. It was then diluted with water and the
to that of G?-chloro-pregnan-SaJ7a,21-triol-3,20-dione.
6,6-chloro-pregnan-3 ,8,5 11,17 a,21-tetrol-20-one and then in
The ?nal product was the diacetate of‘ 6a-chloro-A4
organic layer was separated and washed with water, so
pregnen-17a,21-diol-3,20-dione.
dium bicarbonate solution and again with water to neutral,
Example XIV
dried over anhydrous sodium sulfate and evaporated to 55
dryness under reduced pressure. The residue crystallized
A. suspension of 1 g. of the diacetate of 6a-chloro-A4
from acetone-hexane to give the 21-acetate of 5a, 6a
pregnen-17a,21-diol-3,20-dione in 10 cc. of absolute
oxido-pregnan-lip,17a,21-triol-20-one.
methanol was cooled to 0° C. and mixed with a solu
3 g. of the 2l-acetate of 5a,6a-oxido-pregnan-3,B,17a,21
tion of sodium methoxide prepared by dissolving 120
t'riol-3,20-dione-was dissolved in 100 cc. of chloroform, 60 mg. of sodium metal in‘ 10cc. of absolute methanol; the
cooled to 0° C. and then a slow stream of dry hydrogen
addition was effected with stirring under an atmosphere
chloride was allowed to pass into the solution for 2
of nitrogen. The stirring was continued under nitrogen
hours while the temperature was maintained below 10°
for 1 hour at 0° C. and the mixture was then poured into
C. The mixture was diluted with Water and the chloro
60 cc. of cold saturated aqueous sodium chloride solution
65
form layer was washed with water, dried over anhydrous
containing 0.3 cc. of acetic acid. The precipitate formed
sodium sulfate and evaporated to dryness. Crystalliza
tion of the residue from acetone-furnished the 21-acetate
of 6?-chloro-pregnan-3/3,5a,17a,21-tetrol-20-one.
was collected, washed with water, dried and recrystal
lized from acetone-hexane. There was thus obtained the
free 6a-chloro-A4-pregnen-17a,21-diol-3,20-dione, identi
A solution of 3 g. of the acetate of 6p-chloro-pregnan
cal with the compound of Example I.
3,8,5“,17u21-tetrol-20-one in 150 cc. of acetone was 70
Example‘ XV
cooled to 0° C. and mixed with an 8N solution of chro
A
solution
of
1
g.
of
6a-chloro-A4-pregnen-17a,21-diol
mic acid prepared by mixing 1.7 g. of chromic acid with
3,20-dione in 50 cc. of anhydrous benzene was treated
concentrated sulfuric acid and water. The reagent ‘was
with 4 cc. of propionic anhydride and 300 mg. of p-tolu
added dropwise with stirring and keeping the temperature
enesulfonic acid and the mixture was kept standing at
below 0° C. The stirring was continued for 1 hour at
8,067,219
8
room temperature for 40 hours.
It was then diluted
wherein R is selected from the group consisting of hy
with water and the organic layer was separated, washed
drogen and a hydrocarbon carboxylic ester group of less
with water, aqueous sodium bicarbonate solution and
than 12 carbon atoms.
again with water to neutral, dried over anhydrous sodi
um sulfate and the benzene was evaporated. Crystal 5
3. The 21-monoacetate of 6,8-chloro-A4-pregnen-170:,21
lization of the residue from acetone-hexane furnished
diol-3,20-dione.
6a-chloro-A4-pregnen-l7a,21 - diol - 3,20 - dione
4. A compound of the following formula:
17,21“
propionate.
~ Example XVI
CHzOR
By the method of Example XV, 1 g. of the 2l-cyclo 10
pentylpropionate of 6a-chloro-A4-pregnen-l7¢r,21-diol
3,20-dione, in solution in 50 cc. of anhydrous benzene,
was treated with 2 cc. of acetic anhydride and 200 mg.
XA Cl
of p-toluenesulfonic acid, at room temperature for 24
hours. The acetylation product was worked up as above,
.r/Jj
thus yield yielding 6a-chloro-A4-pregnen-17a,21-diol-3,20
dione 17-acetate-2l-cyclopentylpropionate.
Example XVII
Following the procedure described in Examples XV
and XVI, there were prepared other 17,21-diesters of 6a
l
chloro—A4-pregnen-l7a,21 - diol - 3,20 - dione, wherein the
wherein X is selected from the group consisting of a
double bond between C-1 and C-2 and a saturated link
age between C—1 and C—2, R is selected from the group
ester groups were identical or di?erent from each other.
By this method there were prepared speci?cally the 17,21
dibenzoates, the 17,21-diacetates, the '17,2l-dicyclopentyl
propionates, the 17-acetate, 21-butyrate, etc.
Example XVIII
consisting of hydrogen and a hydrocarbon carboxylic
ester group of less than 12 carbon atoms, R1 is hydrogen
when R is hydrogen and R1 is selected from the group
consisting of hydrogen and a hydrocarbon carboxylic
A mixture of 2 g. of 6a-chlor0-A4-pregnen-17a,2l-diol
3,20-dione diacetate, 100 cc. of tertiary butanol, 0.8 g. of
recently sublimed selenium dioxide and 0.4 cc. of pyridine
hydrocarbon carboxylic ester group of less than 12 car
was re?uxed for 72 hours under an atmosphere of nitro
bon atoms.
gen.
ester group of less than 12 carbon atoms when R is a
5. éa-chloro-At-pregnen-17m,21-diol-3,20-dione.
The mixture was ?ltered, washing the ?lter with
6. The 2l-hydrocarbon carboxylic mono esters of less
than 12 carbon atoms of 6ot-chloro-A4-pregnen-170:,21
40 cc. of hot t-butanol, and the combined ?ltrate and
washings was evaporated to dryness under reduced pres
sure. The residue was dissolved in acetone, treated with
decolorizing charcoal and ?ltered. The acetone was re
moved and the residue was chromatographed on neutral
than 12 carbon atoms of 6a-chloro-M-pregnen-17¢,21
alumina, thus yielding 6a-chloro-A1r‘l-pregnadien-l7a,21
diol-3,20-dione.
diol-3,20~dione.
7. The 17,21-hydrocarbon carboxylic di esters of less
8. The 21-monoacetate of 6a-chloro-A4-pregnen-l7a,21
diol13,20-dione diacetate.
40 diol-3,20-dione.
Eample XIX
9. The 17,21-diacetate of éa-chloro-A‘i-pregnen-170:,21
By the method of the previous example, there was de
diol-3,20-dione.
hydrogenated 6a-chloro-A4-pregnen-17u,21-diol-3,20-dione
1i). 6a-chloro-A114-pregnadien-17a,2l-diol-3,2O-dione.
17-acetate-21-butyrate to produce 60: - chloro - A114 - preg
11. The 21-hydrocarbon carboxylic mono esters of less
than 12 carbon atoms of 6a-chloro-A1'4-pregnadien
nadien-l7a,2l-diol-3,20-dione 17-acetate-2l-butyrate.
Example XX
Following the procedure described in Example XVIII,
17a,21-diol-3,20-dione.
there was introduced an additional double bond between
12. The 17,21-l1ydrocarbon carboxylic di esters of less
than 12 carbon atoms of 6a-chloro-A1’4-pregnadien
C-1 and C-2 of other diesters of hydrocarbon carboxylic
acids of less than 12 carbon atoms 6a-chloro-A4-pregnen
170:,21-(ll0l~3,20—dl021€.
17a,21-diol-3,20-dione, which esters were formed with
identical radicals or different from each other including
the other esters referred to in Example XVII.
17a,2l-di0l 3,20-dione.
13. The 2l-rnonoacetate of 6a-chloro-Alr‘i-pregnadien
14. The 17,2l-diacetate of 6a-chloro-Ald-pregnadiem
17a,21-diol-3,20-dione.
Example XXI
55
By conventional saponi?cation of the esters of 60a
chloro-AL4-pregnadien-l7a,21-diol-3,2O-dione such as the
17,2l-diacetate there was prepared the free 6a-chloro
AM-pregnadien-17,21-diol-3,20-dione.
We claim:
1. A compound of the following formula:
CHzOR
I 5w
60
References Cited in the ?le of this patent
UNITED STATES PATENTS
2,774,775
2,786,855
2,837,464
2,838,540
2,862,939
2,865,914
Korman et al. ________ __ Dec. 18,
Sondheimer et al ______ __ Mar. 26,
Nobile _______________ __ June 3,
Campbell et al ________ __ June 10,
Dodson et al. ________ __ Dec. 2,
Schneider et al. _______ __ Dec. 23,
1956
1957
1958
1958
1958
1958
2,934,546
Ringold et al __________ .__ Apr. 26, 1960
OTHER REFERENCES
Sondheimer et al.: J. Am. Chem. Soc., vol. 75, Dec.
5, 1953, pp. 5930-593.
Meystre et al.: Helv. Chim. Acta, vol. 39, Section III,
1956, No.88, pp. 734-42.
Bowers et al.: J. Am. Chem. Soc., vol. 80, Aug 20,
1958, pp. 4423 and 4424.
Документ
Категория
Без категории
Просмотров
0
Размер файла
566 Кб
Теги
1/--страниц
Пожаловаться на содержимое документа