Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
1053686
The present invention relates to 2,5-furane derivatives
and their production and to intermediates in the said production.
The furane derivatives of the invention are represented
by the following formula
R1~3L CR - CH -- C - R
wherein R represents a lower alkyl group, or a group of the
formula ROOC-(CH2)7, wherein R represen~s hydrogen or a lower
-. 10 alkyl group, each of R2 and R3 represents hydrogen, or R2 and R3 `:.
together represent a further bond between the two carbon atoms,
R4 represents hydrogen, or a lower alkyl group, and R5 represents :
hydroxy, or R4 and R5 together represent an oxygen atom, and R6 .
represents agroup C5Hll,provided that:..~hen-R represents methyl
at least one of R2, R and R is other than hydrogen, and when
l represents methyl, and R4 and R5 together represent an oxygen
atom, R2 and R3 are hydrogen.
The lower alkyl groups of the present compounds are
preferably those having 1-4 carbon atoms, i.e., methyl, ethyl,
. 20 propyl, isopropyl, butyl, isobutyl, and tert.butyl. The R6 group
. is preferably an n-pentyl group.
The compounds of the invention have useful biological
. ~ ~ properties combined ~ith a relatively low toxicity. Thus, they
.~ have a controlling effect upon the hormone production of corpus .
. .~ .
. ~ ; ..luteum, and are ln that respect almost as effective as the
- ~ prostaglandin PGF2~ without however, showing any side effects. : :
. ~ The following schemes of reaction illustrate the
. ~ production:~of the compounds of the invention
$`~ `
r
i: :
1053686
~ ( 2)7 ~ O ~ CHO + C5HllCOCH3 NaOH
., O
l~O-C-(CH2)7 _ ~0 ~ _ CH=CHCOC5H11 3( 2 5)2
II CH30H
CH O-C-(CH ) ~ CH=CHCOC5H
III
I + CH3(CH2)4-RC-cH2 n (0CH3)2 > III
O O
II + C2H5H 3 2 4)2 ~
~ NaBH
C2H40-C-(CH2)7 ~ 0 ~ CH C 2 5 11
.' IV
'` C2H50-C-(CH2)7 ~ CH=CH2CHOHC5H
~ IVa
,' H2, Raney-Cu
C2H50-C(CH2)7 ~ CH2CH2COC5H 4 >
~: V
C2H50-C- (CH2) ~CH2CH2CHOHC5H
~: VI
VI 2 3 > HO-C-(CH2~7 ~ CH2CH2CHOHC5H
VIa
~, .
. ~ .
, ~ .
1053686
.
K2C3 HO-C- (Cl~2) 7 ~CH2CH2COC5Hll
O
VII
CH3 ~L CHO + C5HllCOCH3 - ~
VIII
CN3~LCH=CH-COC5H H4
IX
.
CH InL CH--C
3 o -- H--CHOHC5Hl 1
V
VII THCS,HMDS ,~ [CH3~5iOOC-(CH2)~CH2)2cOc5Hll]
XI
1. CH3MgBr ~ I H3
2~ H30 `: ~ HOOC (CH2) 7 ~ y_ ~CH2) 2- ~ - C5Hll
`: OH `~
` ` XII ~-
, ~`H~ BF3(C2H5)20 ~ ~ ~ CH30C~(CH2)~7 (CH2)2 - C - C5Hll - :
. ~ ~ o : OH
. , ~ : XIII
R ~CII--CHCOC5H
2 `~ C2H5 ` XVII
H ~ CH ~ ) ~ XV I I 1
. ~
4-
-`- 1053686
H2, Raney Ni R ~ (CH2)2COCs~ll
-CH3 XIX ~
C2~5 XX
-CH ( CH 3 ) 2 XXI
b I
NaBH4 . ~ R ~, O ~(CH2) 2CHOHC5H
R:
c --CH3 XXI
--C2H5 XXIII
, -CH (CH 3 ) 2 XXIV
j~ The starting material for the production of the
¦`~ compounds of the invention are furane derivatives of the formula
.:. ~ - :
~ ~ R ~CHO
.~ . ,
wherein Rl is as hereinbefore defined, which can be produced from
known compounds of the formula
R ~ -
or oxample by formylating according to Vilsmeyer.
The starting aldehydes are condensed with the appropriate
àlka~n-2-one, e.g. 2-heptanone, or a 2-oxoalkyl-phosphonic acid
dimethyl~ ester~to estab1ish a 3-oxo-l~alkenyl group at the 5-
~position~of the furane ring and optionally hydrogenating at the --
double bond in l-positionof said side chain catalytically, and
educing the keto group with sodlum horohydride or subjecting
O~ the-keto group to a Grignardation using an alkyImagnesium halide
as~the Grignard reagent.
~ When Rl represents the group ROOC-(CH2)7-, wherein R is
: ~ ~ --5--
~,
" , . ' ., ' . ' ' i ~ , . -:. , ' ,
1053686
hydrogen, the carboxyl group may subsequently be esterified to
yield esters of the invention or, if the resultin~ compound is an
ester, it may be saponified to yield the corresponding acid.
The introduction of the side chain in 5-position is
preferably carried out at room temperature in solution in an
alkanol, e.g. methanol or ethanol.
Suitable catalysts for the hydrogenation are Raney
nickel, Raney copper, and noble metal catalysts, e.g. palladium.
The following examples are illustrative of the production
of the present compounds, the various compounds being identified
by the numbering in the above schemes of reaction.
Example 1
8-[5-(3-Oxo-l-octenyl)-2-furyl]-octanoic acid (II)
I (9.17 g, 0.0364 mole), produced by formylating iuryl-
- 2-octanoic acid, was dissolved in methanol (60 ml), and the
solution was cooled to -5C. Aqueous 20% sodium hydroxide (9.1 g)
was added in one portion with stirring. To the resulting mixture,
2-heptanone t5.05 g, 0.0444 mole) was added with stirring over a
" period of 10 minutes at a temperature of 18-20C. The stirring
. 20 was continued for one hour at the same temperature, and then for
additional 16 hours at room temperature. The reactlon mixture was
poured into water (130 ml) and adjusted to pH 7.2 with 3N acetic
acid (9.2 ml). The resulting yellow crystals`were isolated by
.~. ~ .
filtration and washed with water (30 ml). The filtrate (F) was -
collected. The wet cake of crystals was suspended in a mixture of
water (80 ml) and ether (80 ml) and stirred. The resulting
. ~ emulsion was neutralized to pH 7 with 3N acetic acid. The
ethereal layer was separated. The aqueous layer was extracted
A ~. . .
~- ~ with ether (50 ml). The combined ethereal extracts were washed
with water (50 ml) and then dried over magnesium sulfate. The
dried ethereal solution was evaporated to dryness from a water
bath (60DC), at last under 15 mm Hg. 6.21 g of crude II were
; :
~.
. . , . - , .
1053686
hereby obtained as a yellGw oil, which solidified at room temp-
erature.
The above filtrate (~) was stirred with ether (50 ml)
and the pH of the emulsion was adjusted to 7 with 3N acetic acid.
The ethereal layer was separated, and the aqueous layer extracted
with ether (50 ml). The combined ethereal extracts were washed
with water (50 ml), dried over magnesium sulfate, and the ether
removed ~y distillation from a water bath (60~C), at last under ~ -
15 mm Hg. Chromatography of the yellow, oily residue (5.30 g) on
silica gel (150 g, 60-120 mesh, from sDH Chemicals Ltd.) and
elution with increasing concentration of acetone in n-hexane gave
2.20 g of crude II.
The combined crude products were crystallized
' from n-hexane (250 ml). 7.45 g (61%) of II were hereby obtained as
pale, yellow crystals, m.p. 58-59C.
Calculated for C20H30O4 (334.4): C 71.8~ H 9.0
Found : C 71.7, H 9.0
Example 2
8-[5-(3-Oxo-l-octenyl)-2-furyl]-octanoic acid methyl ester (III)
A. II (2.52 g, 0.00755 mole), methanol (30 ml), and ethyl ether-
~
~- borontrifluoride complex (0.24 g) were stirred and heated under
ref-lux for 1 hour. After cooling, the reaction mixture was poured
into ice-water (150 ml) and extracted with two 80-ml portions of
ethcr. The combined ethereal extracts were washed with cold 10%
sodium oarbonate ~50 ml) and then with two 50-ml portions of cold
-~ater. The ethereal solution was dried over magnesium sulfate and
e~aporatèd to-dryness from-a water bath (60C),-at last under 15
Hg. Distillation under nitrogen of the residual oil (2.46 g)
gave 2.07 g (79%) of III, bo;3 202~204C, nD 1.5262.
~-~; 3Q C,alculated for C21H32O4 (348.5): C 72.4, H 9.3 one OCH3 8.9
Found : C 72.5, H 9.2 OCH3 8.9
~, -
l~ ~ B. 50% sodium hydride in mineral oil (0.96 g, 0.02 mole) was-
i :
~:
; -7-
_.. , . . .. . . . -. - .... . . ~ .. :
... . . . .
1053686
suspended in dry 1,2-dimethoxyethane (200 ml), The slurry was
cooled to 15C and stirred vigorously with a mechanical stirrer.
(2-Oxoheptyl)-phosphonic acid dimethyl ester (Wadsworth et al:
J.A.C.S. 83 (1961) 1733) (4.44 g, 0.02 mole) was added dropwise
over a period of 30 minutes, the reaction temperature being kept
at 15-20C. After the addition, the suspension of a white,
voluminous precipitate was stirred for 1 hour at room temperature.
A solution of I (5.04 g, 0.02 mole) in 1,2-dimethoxyethane (30 ml)
was added dropwise over a period of 30 minutes to the stirred
suspension, maintained below 25C. The resulting turbid, yellow
solution was stirred at room temperature for 1.5 hours. The
solvent (200 ml) was distilled off from a water bath (70C) under
reduced pressure (40 mm Hg). After cooling, the oily residue was
diluted with cold water (300 ml) and extracted with two 200-ml
portions of ether. The combined ethereal extracts were washed
with two 100-ml portions of water and then dried over magnesium
` sulfate. The dried ethereal solution was evaporated to dryness
from a water bath (60C), at last under 15 mm. The residual
yellow oil was purified by distillation under nitrogen. 6.34 g
;
~91%) of III was hereby obtained as a yellow liquid, bo 1194-200C,
1.5256. In tlc it had the same Rf values in different solvents
as the compound obtained by method A.
Example 3
8-15-~3-Oxo-l-octenyl)-2-furyl]-octanoic acid ethyl ester ~IV)
,: .
A mixture of II (9.94 g, 0.0298 mole), ethanol (190 ml),
;and ethyl ether-borontrifluoride complex (0.97 g) was stirred and
heated: under-reflux-for 1.5 hours.- After cooling, the reaction
mixture-was poured into ice-water (600 ml) and extracted with
three 300-ml portions of ether. The combined ethereal extracts
-h ~ ; .
~ 30 were washed with cold 10% sodium carbonate (100 ml~ and then with
; 200-ml portions of cold water. The ethereal solution was dried -~
~ ~ over magnesium sulfate and evaporated to dryness from a water bath
~ ~ '
~; -8-
1~53686
(60C), at last under 15 mm Hg. The resid~al yellow oil (9.84 g)
was purified by distillation under nitrogen from a potassium
acetate coated flask giving 8.57 g (79%) of IV, b 2 198-201~C,
n25 1.5217.
Calculated for ~22H344 (362.5): C 72.9, H 9.5, OC2H5 12.4
Found : C 73.0, H 9.5, OC2H5 12.3
Example 4
8-[5-(3-Oxooctylj-2-furyl]-octanoic acid ethyl ester (V)
IV (1.74 g, 0.0048 mole), ethanol (25 ml), and Raney
10 cooper (Ponomarev et al., J. Gen. Chem. USSR 30 (1960) 584) (0.75
g) were shaken under 80 atmospheres of hydrogen for 6 hours at
30C. After filtration, the ethanol was distilled under reduced
pressure form a water bath (60C). Ether (30 ml) was added to the
residue, and the turbid solution was filtered (G4, Celite a
trademark). The ethereal solution was evaporated to dryness from
a water bath (50C) under reduced pressure, at last under 15 mm
Hg. The residual oil was purified by distillation under nitrogen.
1.51 g t86%) of V was hereby obtained as an almost colorless oil,
bo 2 178-181C, nD 1.4700.
i~ 20 Calculated for C22H36O4 (364.5): C 72.5, H 10.0, OC2H5 12.4
Found : C 72.3, H 10.0, OC2H5 12.4
Example 5
8-~5-(3-Hydroxyoctyl)-2-furyl]-octanoic acid ethyl ester (VI)
V (1.25 g, 0.003~3 mole) was dissolved in absolute
ethanol ~70 ml), and the solution was cooled to -5C. Sodium
'~ tetrah~droborate ~O.50 g, 0.0132 mole) was added portionwise
during ~ minutes with stirring.- The--turbi-d solution was stirred
at~0-5~C--for 15 minutes, then at room temperature for 1 hour. The
colorless solution was poured into ice-water (250 ml). 1.5 N
30 sodium hydroxide (10 ml) was added with stirring to the resulting ~
emulsion. The stirring was continued for 15 minutes. The white
emulsion was extracted with three 100-ml portions of ether. The
_ g _
: . . , : , . ,
1053686
combined ethereal extracts were washed with cold water (100 ml),
dried over magnesium sulfate, and the solvent was removed by
distillation from a water bath (60C), at last u~der 15 mm Hg.
Distillation of the residual oil (1.34 g) gave 1.18 g (94%) of VI
as a colorless oil, b 1 172-175C, nD 1.4731.
Calculated for C22H38O4 (366.5): C 72.1, H 10.5, OC2H5 12 3
Found : C 72.2, ~ 10.5, OC2H5 12.4
Example 6
8-[5-(3-Oxooctyl)-2-furyl]-octanoic acid (VII)
A mixture of V (5.10 g, 0.014 mole), methanol (180 ml),
and 20% potassium carbonate (60 g) was stirred and heated under
reflux for 1 hour. The turbid solution was concentrated to 1/4 of
the volume by distillation from a water bath (60C) under reduced
pressure (50 mm Hg). The residue was diluted with water (300 ml),
and the resulting clear solution was acidified to pH 6 with acetic
acid. The emulsion was extracted with two 150-ml portions of
~ ether. The combined ethereal extracts were washed with two 100-
t ml portions of water, and then dried over magnesium sulfate.
Ether was distilled off from a water bath (60C), at last under
20 15 mm Hg. The yellow, oily residue (4.62 g) solidified at room
temperature. Purification by crystallization from n-hexane (40
~` ml) gave 3.54 g (75%) of VII as slightly yellow crystals, m.p.
`t ~64-65C.
Calculated for C20H32O4 (336.5): C 71-4~ H 9-6
Found - : C 71.2, H 9.6
~ .
~` ~ Exàmple ?
. ,
1-(5-Methyl-2-furyl)-1-octen-3-ol (X)
~- - The starting màterial, 1-(5-methyl-2-furyl)-1-octen-3-
one (IX, which is known (Chem.Abstr. 74 (1971) 141,418 g), was
30 prepared from VIII (J.Org.Chem. 22 (1957) 1269) after the
direction given in the literaturé (J.A.C.S. 70 (1948) 2695).
` IX (1.65 g, 0.008 mole) was dissolved in absolute
-10-
~053686
ethanol (200 ~1), and the solution was cooled to 0C. Sodium
tetrahydroborate (0.70 g, 0.0185 mole) was added in one portion
with stirring. The turbid solution was stirred at 0-5C for 15
minutes and then at room temperature for 20 hours. The
solution was concentrated to 1/4 of the volume by distillation
from a water bath (40C) under reduced pressure (50 mm Hg). The
residual solution was cooled to 10C, and then cold water (800 ml)
and N sodium hydroxide (25 ml) were added successively with
stirring. The stirring was continued for 15 minutes at room
temperature and then the pH of the emulsion was adjusted to 7.8
by addition of 3N acetic acid. The reaction mixture was
extracted with two 150-ml portions of ether. The combined organic
extracts were washed with water ~100 ml) and dried over magnesium
sultate. The ethereal solution was evaporated to dryness from a
water bath (60~C) under reduced pressure, at last under 15 mm Hg.
The residual oil (1.67 g) was purified by distillation under
nitrogen. 1.13 g (68%) of X were hereby obtained as a yellow
liquid, bo 2 97-99C, nD 1.5166-
Example 8
~, .
8-[5-~3-Hydroxyoctyl)-2-furyl]-octanoic acid (VIa)
'~ A mixture of VI (2.73 g, 0.00745 mole), methanol (100
~:: ml), and 20% aqueous potassium carbonate solution (30 ml) was
,~ stirred and heated under reflux for 1 hour. The turbid solution
~`~ was concentrated to 1/4 of the volume by distillation from a water '-~
i`
`~r~ bath (60C) under reduces pressure (60 mm Hg). The residue was
~ diluted with water (100 ml~ and adjusted to pH 7 with acetic acid
`i (2.7 ml3. The,resulting emulsion was extracted with two 80-ml
~ portions of ether. The combined ethereal extracts were washed
,~
~` ` with water (100 ml) and then dried over magnesium sulfate. Ether
i
`~I 30 was distilled off from a water bath (50C), at last under 15 mm Hg.
i'~ The yellow, oily residue (2.58 g) was purified by crystallization
, from petroleum ether (boiling below 50~C) (450 ml). 2.13 g (84~)
~ '` '.
-11-
1053686
of VIa were herehy obtained as almost white crystals with m.p.
43-45~C.
20 34 4 ( 38.5): C 71.0 H 10.1
Found : C 70.8 H 10.1
Example 9
8-[5-(3-Oxooctyl)-2-furyl]-octanoic acid methyl ester
.
- III (11.37 g, 0.0326 mole), methanol (150 ml), and
Raney nickel (2.5 g) were stirred at room temperature under 1
atmosphere of hydrogen, until one molequivalent of hydrogen had
reacted. After filtration, the solvent was removed by distilla-
tion from a water bath (60C) under reduced pressure, at last
under 15 mm Hg. The residual, light yellow oil (11.4 g) was
; purified by preparativetlc (thin layer chromatography) on silica
gel (mixture of petroleum ether (b.<50C) and ether ~2:1) as
eluent). 7.25 g of the title compound were obtained as a yellowish
oil. Further purification by distillation under nitrogen gave
` 7.05 ~ (62%) of the title compound as an almost colourless oil,
bo o7 172-180C, nD 1.4723.
Calculated for C21H34O4 (350.5): C 72.0, H 9.8, OCH3 8.8
20 Found : C 71.8, H 9.9, OCH3 9.0
c Example 10
;i'~ ' ~ 8-~5-(3-Hydroxyoctyl)-2-furyl]-octanoic acid methyl ester -~
~ .
,~.; - .
The ester of Example 9 (1.61 g, 0.0046 mole) was
dl-solved in methanol (30 ml), and sodium tetrahydroborate (0.80
g, 0.021 mole) was added at -10C with stirring. The stirring was
; ~contlnued for 90 minutes, the temperature of the reaction mixture ~ -
increasing to 22-25C. The resulting solution was poured into
ice-water (200 ml). 1.5N aqueous sodium hydroxide solution ~10
` ml~ ~as then added, and the emulsion was stirred for 15 minutes.
~`~30 The reaction mixture was extracted with three 100-ml portions of
~ether. The combined organic extracts were washed with two 100-ml
portions of water and dried over magnesium sulfate. The ethereal
.
~ -12-
.~ .
1053686
solution ~as evaporated to dryness from a water bath ~60C) under
reduced pressure (15 mm Hg). The residual oil (1.59 g) was
purified by distillation under nitrogen. 1.50 g (93%) of the
title compound were obtained as a colourless oil, bo o7 176-178C,
n D 1.4759.
21H36O4 (352.5): C 71.6, H 10 3 OCH 8 8
Found : C 71.7, H 10.5, OCH3 8.7
Example 11
8-15-(3-~ydroxyoctyl)-2-furyl]-octanoic acid
A mixture of the ester of Example 10 (2.73 g, 0.0077
; mole), methanol (100 ml), and 20% potassium carbonate (30 ml) was
stirred and heated under reflux for one hour. The colourless
solution was concentrated to one fourth of the original volume by
distillation from a water bath (60~C) under reduced pressure (60
mm Hg). The residue was diluted with water (100 ml), and the
resulting turbid solution was acidified to pH 6 with acetic acid.
The emulsion was extracted with two 100-ml portions of ether. The
combined ethereal extracts were washed with two 100-ml portions of
water and then dried over magnesium sulfate. Ether was distilled
off on a water bath (60C), at last under 15 mm Hg. The yellow,
oily residue (2.58 g) solidified at 10C. Purification by
crystallization from petroleum ether (b.<50C) (450 ml) gave 2.13
g (81%) of the title compound as white crystals with m.p. 43-45C.
20 34 4
Found : C 70.8, H 10.1
` Example 12
8-[5-(3-Hydroxy-3-methyloctyl)-2-furyl]-octanoic acid methyl
ester (XIII)
~ Vii (4.50 g, 0.0133 mole), pyridine (25 ml), hexa-
,~ 30 methyldisilazan (HMDS) (7.2 ml), and trimethyl silylchloride (TMCS)
(2.4 ml) were mixed, and the mixture was left overni~ht protected
from moisture. The suspension was then filtered in a dry
.
-13-
. ~ ~
. -, . .
- 1053686
atmosphere, and the filtrate was evaporated on a water bath (80C)
under reduced pressure (10 mm Hg). The residue was mixed with
dry ether (50 ml), and the mi~ture was filtered to remove a small
amount of insoluble material. The filtrate was cooled to 2C in
a dry nitrogen atmosphere, and a 3.7M ethereal solution of methyl
magnesium bromide (7.8 ml, 0.0289 mole) was added dropwise with
stirring over a period of 25 minutes at about 10C. The resulting
suspension was stirred overnight at room temperature. It was
then added to a mixture of N HCl (32 ml) and water (120 ml), the
temperature of which was 5C, and the resulting mixture was
stirred for 90 minutes. The ethereal layer was then separated,
and the aqueous phase was extracted with ether (30 ml). The
combined ethereal extracts were extracted with 0.5N aqueous
sodium hydroxide (40 ml). The aqueous extract was made acidic
with 0,5N hydrochloric acid (42 ml) and extracted with two 25-ml
portions of ether. The combined ethereal extracts were dried with
magnesium sulfate and evaporated to dryness from a water bath
(70C), at last under lS mm Hg. The residual crude acid XII
(4.23 g) was esterified in a mixture of methanol (50 ml) and ethyl
20 ether - borontrifluoride complex (0.5 ml) as described in Example -
2 to give the crude methyl ester XIII (4.2 g). This crude ester
was purified by chromatography using a column of silica gel and
petxol ether - ether (1:1) as eluent to give 2.1 g of crude oil.
: The distillation under nitrogen of this crude oil gave 1.83 g
~(37S) of XIII, bo 3 178-180C, nD 1.4749.
Calculated for C22H38O4 (366.5): C 72-1, H 10-5~ OCH3 8-5
` Found : C 71.5, H 10.4, OCH3 8.6
The NMR spectrum was in accordance with the presumed
structure for XIII.
~30` Example 13
~-8-¦5-(3-Hydroxy`-3-methyloctyl)-2-furyl~-octanoic acid (XII)
i.:: ' .
mixture of XIII (0.91 g, 0.0025 mole), methanol ` `
, . , ~ . ..
-14-
.
1053686
(10 ml), and 20~ potassium carbonate (5 ml) was stirred and
re~luxed for 90 minutes. The clear yellow solution was mixed with
water (15 ml) and acidified to pH 5-6 with acetic acid. The
emulsion was extracted with two 15-ml portions of ether. The
comhined ethereal extracts were dried over magnesium sulfate.
Ether was distilled off from a water bath (60C), at last under
0.1 mm Hg. The yellow, oily residue (0.86 g) was purified by
chromatography on three 20 x 20 cm preparative tlc plates (Merck
silica gel 60F254-2 mm layer), and the isolated crude XII herefrom
was distilled at 175-185C and 0.03 mm Hg to give 0.63 g XII (71%)
as a light yellow oil, nD 1.4844.
Calculated for C21H36O4 (352.5): C 71.~, H 10-3
Found : C 71.7, H 10.3
Example 14
1-_(5-Alkyl-2-furyl)-octen-3-ones (XVII, XVIII)
To the stirred solution of a 5-alkylfuraldehyde (0.0666
mole) and 2-heptanone (9.3 ml, 7.58 g 0.0666 mole) in methanol
(25 ml) aqueous 20% sodium hydroxide (1.8 ml) was added dropwise
at 10-12C over a period of 10 minutes. The clear yellow
. 20 solution was stirred at the same temperature for onehour, then for
18 hours at room temperature. The pH of the resulting mixture was
adjusted to 7 by addition of acetic acid. The reaction mixture
was poured into water ~100 ml) and extracted with two 70-ml
portions of ether. The combined organic extracts were washed with -
~`~ three 50-ml portions of ether and dried over magnesium sulfate.
i~ The ethereal solution was evaporated to dryness from a water bath
t70C) under reduced pressure, at last under 15 mm Hg. The
residual oil was purified by distillation under 10 mm Hg.
R 10 mm nD5 m. yield
, 30 C C %
2H5 166-174 41 64
CH(CH3)2 174-182 1.5415 57
-15-
. . . ~ . . .
. . . .
1053686
formula molecular calculated found
weiaht C H C H
C2H5 C14H202 220.3 76.3 9.2 76.2 9.2
CH(CH3)2 C15H22O2 234.3 76.9 9.5 76.6 9-4
Example 15
1-(5-Alkyl-2-furyl)-3-octanones ~XIX-XXI)
A 1-(5-Alkyl-2-furyl)-1-octen-3-one (0.03 mole),
methanol (150 ml), and Raney nickel (10% by weight of the olefin)
10 were stirred at room temperature under 1 atmosphere of hydrogen,
until one molequivalent of hydrogen had reacted. After filtration,
the solvent was removed by distillation from a water bath (60C)
under reduced pressure, at last under 15 mm Hg. The residual light
yellow oil was purified by preparative thin layer chromatography.
s Silica gel has been used as adsorbent and a mixture of ether and
petroleum ether (b.<50C) (1:8) as developing solvent. The
adsorbent was scraped off the glass plates and stirred for 1
hour with ether. After filtration, the solution was evaporated
~ to dryness from a water bath (60C) under reduced pressure, at
;j 20 last under 15 mm Hg. The residual oil was purified by distillation
` under reduced pressure.
~ C nD5 yield
.~
~` CH3 140-142 1.4687 ~20DC) 71
C2H5 147-150 1.4675 86
CH(CH3)2 158-159 1.4651 71 - - ~ ---
. ..
- R ~ormula molecula~ calculated ~ound
~` weight C H C H
r,~ ~ .
:~ 30 CH3 C13 20 2 208.3 75.0 9.7 74.3 9.8
2 5 C14H22O2 222,3 75.6 10.0 7S.5 10.1
CH(CH ) C15 24 2 236.3 76.2 10.2 76.1 10.3
-16-
1053686
Example 16
5-Alkyl-~-pentyl-2-furanpropanols (XXII-XXIV)
A 1-(5-alkyl-2-furyl)-3-octanone (XIX-XXI) (0.015 mole)
was dissolved in ethanol (90 ml), and sodium tetrahydroborate
(2.40 g, 0.064 mole) was added at -10C with stirring. The
stirring was continued for 90 minutes, the temperature of the
reaction mixture increasin~ to 23-25C. The colourless solution
was poured into ice-water (300 ml). 1.5N aqueous sodium hydroxide
(20 ml) was then added, and the emulsion was stirred for 10
minutes. The reaction mixture was extracted with three 100-ml
portions of ether. The combined organic extracts were washed with
two 100-ml portions of water and dried over magnesium sulfate.
The ethereal solution was evaporated to dryness from a water bath
(60C) under reduced pressure, at last under 15 mmHg. The
i~ .
~ residual oil was purified by distillation under reduced pressure.
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R blCO mm nD5 yield
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CH3 148-160 1.4744 (20C) 95
C2H5 152-155 1.4725 93
CH(CH3)2 160 1.4701 91
,
R formula molecular calculated found
~eight C H C H
.
CH3 C13H2202 210.3 74.2 10.5 74.1 10.5
C2H5 C14H2402 224.3 75.0 10.8 74.8 10.7
CH(CH3)2¦ C15H2602 238.9 5.6 11.0 75.4 11.2
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