Note: Descriptions are shown in the official language in which they were submitted.
1 1 63642 TC-ELDE~-5 ~
This application i5 a di~vision of Canadian Application
Serial No. 346,784 filed February 29, 1980.
This invention relates to a process for making
a-loweralXylfurocourr~rins and to novel intermediates produced
therein.
Phenols can be converted to cl-methylbenzofurans by a
five-step process which involves O-allylation, Claisen
rearrangement to an o-allylphenol, acetylation of the phenolic
hydroxyl group, addition of halogen to the allylic double
bond, and cyclization in an alkaline alcoholic medium.
L. Claisen, Ann., 418, 69 (1919) and Ber., 53, 322 (19201.
That approach has been successfully utilized to convert
7-hydroxycoumarins to a-methylfurocoumarins, K. D. Kaufman,
J. ORG. CHEM., 26, 117 (1961) and U. S. Patent 3,201,421, including
4,5',8-trimethylpsoralen which was obtained from 4,8-dimethyl-
-7-hydroxycoumarin in 28~6 overall yield. Trimethylpsoralen,
under the generic name Trioxsalen, has been extensively used
with ultraviolet radiation in the treatment of vitiligo, T. B.
Fitzpatrick, J. A. Parrish, and M. A. Pathak, in "Sunlight and
Man", University of Tokyo Press, Tokyo, Japan, 1974, p.
783-791, and has been recommended in psoriasis therapy,
S. W. Becker, Aust. J. Derm., 18, 15-19 (1977). Thus a con-
venient and efficient synthesis of a- loweralkylfurocoumarins.
is of contemporary practical interest.
OBJECTS OF THE INVENTION
It is an object of the invention to provide an improved
process for making a- loweralkylfurocoumarins. It is a further
object of the invention to provide novel compounds useful
as intermediates in the preparation of a-laweralkylfurocounarins.
It is another object of the invention to provide novel
processes for the production of such intermediates. It is an
additional object of the invention to avoid the disadvantages
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1 ~ 63642
of the prior art and to obtain such advantages which will
appear as the description proceeds.
BRIEF DESCRIPTION OF THE INVENTION
The invention relates to a process which comprises pro-
viding a 7-(2~halo-loweralk-2Lenyloxy)coumarin having an
active hydrogen in the ortho position and heating it, prefer-
ably but not necessarily, in a basic tertiary amine solvent,
for a time and at a temperature such that a Claisen rearrange-
ment is effected. The heating is continued at least until the
predominant product is the intermediate (~-h'alo-loweralk-2~enyl)-
7-hydroxycoumarin, preferably until the predominant productiS the
~-loweralkylfurocoumarin, and the reaction is most advantage-
ously conducted without isolation of the intermediate product.
Advantageously, the reaction may include the step of heating,
preferably in the presence of a hydrogen halide acceptor, a
1,2-dihalo-loweralk-2-ene with a 7-hydroxycoumarin having an
active hydro~e~ in the ortho position, to provide sta~ing material.
The Claisen rearrangement of ~-haloallyl ethers is of a
type known in the art as l'abnormal", D. S. Tarbell, Org.
Reactions, 2, 10 (1944). These abnormal rearrangements
usually proceed in poor yield. Thus, the rearrangment of
~-bromoallyl phenyl ether has been reported to proceed in
30% yield in boiling decalin. [J. von Braun, Ann., 449,
264, (1926)J. Elowever, Hurd and Webb ~C. D. Hurd and C. N.
Webb, J. Amer. Chem. Soc., 58, 2190 (1926)] were unable to
:
obtain a pure product from the same rearrangement in decalin
or fluorene or by heating without a solvent,but isolated
minor amounts of the phenol and the cyclized product ~-methyl-
benzofuran from the Claisen rearrangement of ~-chloroallyl
.
phenyl ether, It is therefore surprising that, in the
process of the invention, there are obtained high yields
both of (2~halo-loweralk-2'enyl)-7-hydroxycoumarin and -lower-
-2-
:
TC ELDER-5
~ ~ 6364 ~
alkylfurocoumarin. This is even more surprising in view of
the fact ~hat Anderson et al., JCS Chem. Comm., 1974, p. 174,
was unable to obtain any cyclized product from chloroallyl
phenyl ethers after 48 hours in boiling N,N-diethylaniline.
To obtain a cyclized product, namely, a 2-methylbenzo [b] furan,
it was necessary for Anderson et al. to treat the ortho-
chloroallyl phenol under acidic conditions in a separate
s~ep. Thus, the discovery that 7-(2'-halo-loweralk-2'enyloxy)-
coumarins can be converted directly to ~c~era ~ lfuroco ~ rins,
in the presence of an acid-binding agent, and especially
most conveniently by boiling in N,N-diloweralkylaniline
or like basic solvent, is entirely unexpected.
The invention is particularly directed to the preparation
of trimethylpsoralen and analogues thereof from a (2'halo-
-loweralk-2Lenyl)-7-hydroxycoumarin having a reactive hydrogen
in the 6- position and a substituent in the 8- position
effective to block the formation of isopsoralenes. In this
process, both the starting compound, that is, a 7-(2'-halo-
-loweralk-2'enyloxy)coumarin having an active hydrogen
in the 6~ position and a blocking group in the 8- position
and the 6-(2~halo-loweralk-2~enyl)-7-hydroxycoumarin are
novel intermediates which are readily converted to the corres-
ponding psoralenecompounds on heating in a N,N-diloweralkyl-
aniline or like tertiary amine solvent for a time and at a
temperature such that rearrangement and cyclization is
effected.
The isopsoralenes are prepared in a like manner from
7-(2Lhalo-loweralk-2~enYlOXy)couma~ins havin~ an active
hydrogen in the 8- position. The starting ether for this
conversion was prepared by Shamshurin et al., Trudy Uzbekskogo
Gosudarst Univ. (N.S.), No. 25, ~ m., No. 1, 1-8 (1941), but
its conversion either to a (2Lhalo-loweralk-2~enyl)-7-
-hydroxycoumarin or to an ~-loweralkylfurocoumarin has not been
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1 ~ 636~Z
reported.
Tlle process of th~ invention may b~ illustrated by
the followiny flow diagram:
Rl R
~o R6CH=CX-CHRsO ~ 4 o
R~ J-R R-6--CH=CX--CHR5X R~
R2 Rl Hydrogen Halide Acceptor 3 ~ ~-R
I / II
R4=blocking group R4=hydrog~n
3=H
~CH-CX--CHRs
R4 ¦
HO ~ ~ HO ~ ~-~o
R CH=CX_CHR6- ~ -R R- ~ -R
R2 Rl R2 R
- III IV
R6
R5C~2 ~ O 5C 2 ~
6 R --R
R2 Rl
In Formula I, R, Rl, R2, R3, and R4 can be hydrogen,
alkyl, and lower-alkoxy, provided at least one of R3 and R4
:::
is hydrogen. ~In Formula II, additionally, R5 and R6 can be
hydrogen or lower-alkyl. In Formula III, R4 must be a
blocking group, that is, other than hydrogen and, for the con-
4-
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1 1 63642
version to compound IV, the R4 must be hydrogen, in which case
R3 can be hydrogen also. The X is halogen, advanta~eously,
chlorine or bromine. Compounds I, V, and VI are known
compounds, as is compound II where Rl is methyl and all
of the other R's are hydrogen. Compounds III and IV are
novel intermediates useful in the production of compounds V
and VI, and compound II, except for the case noted above, is
a novel compound useful as an intermediate in the production
o~ compounds III and V.
Suitable known starting compounds of ~ormula I include:
7-hydroxycoumarin,
7-hydroxy-4-methylcoumarin,
7-hydroxy-8~methylcoumarin,
7-hydroxy-4,8-dimethylcoumarin,
7-hydroxy-3,6-diethyl-4-methylcoumarin,
7-hydroxy-4-methyl-6-octadecylcoumarin,
7-hydroxy-3,4,5-trimethyl-8-propylcoumarin,
7-hydroxy-5-methoxy-4-methylcoumarin,
7-hydroxy-8-methoxycoumarin, and
7-hydroxy-8-methoxy-4-methylcoumarin.
Representative examples of known 1,2-dihalo-loweralk-
enes suitable for use in the process include:
2,3-dichloropropene,
2,3-dibromopropene,
2,3-dichloro-1-pentene,
1,2-dichloro-2-pentene,
3,4-dibromo-2-pentene,
2,3-dichloro-1-butene,
1,2-dichloro-2-butene,
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1 1 63642
1,2-dibromo-2-decene,
2,3-dibromo-1-hexene,
1,~-dibromo-2-hexene,
3,4-dibromo-6-methyl-2-heptene, and
3,4-dibromo-2-nonene.
Representative examples of compounds II (flow diagram on
page 4) which can be prepared from the foregoing or similar
known starting materials, are as follows:
4,8-dimethyl-7-(2'-bromoallyloxy3coumarin,
4,8-dimethyl-7-(2'-chloroallyloxy)coumarin,
4-methyl-7-(2'-bromoallyloxy)coumarin,
7-(1'-ethyl-2'-chloroallyloxy)coumarin,
7-(1'-methyl-2'-bromobut-2'-enyloxy)-3,4,5-trimethyl-
8-propylcoumarin,
7-(1'-isobutyl-2'-bromobut-2'-enyloxy)-4-methyl-6-
octadecylcoumarin,
7-(2'-bromodec-2'-enyloxy)-8-methoxycoumarin,
7-(2'-bromoallyloxy)-8-methoxycoumarin,
7-(2'-chloroallyloxy)coumarin,
7-(2'-chloropent-2'-enyloxy)-4,8-dimethylcoumarin, and
7-(2'-bromoallyloxy)-8-methylcoumarin~
Representative examples of compounds III (flow diagram)
which can be prepared by the abnormal Claisen reaction from
the foregoing and similar starting materials, are as follows:
6-(2'-chloroallyl)-4,8-dimethyl-7-hydroxycoumarin,
: 6-(2'-bromoallyl)-4,8-dimethyl-7-hydroxycoumarin,
6-(2'-bromoallyl)-7-hydroxy-8-methoxycoumarin,
6-(1'-ethyl-2'-chloroallyl)-4,8-dimethyl-7-hydroxy-
coumarin,
6-(1'-methyl-2'-bromobut-2'-enyl)-7-hydroxy-3,4,5-
trimethyl-8-propylcoumarin,
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1 J 63642
6-(2'-bromoallyl)-7-hydroxy-8-methylcoumarin, and
6-(1'-heptyl-2'-bromoallyl)-7-hydroxy-8-methoxycoumarin.
Representative examples of compounds IV (flow diagram)
which can be made from the foregoing and similar starting
materials are as follows:
8-(2'-bromoallyl)~7-hydroxy-4-methylcoumarin,
8-(2'-chloroallyl)-7-hydroxycoumarin,
8-(2'-chloropent-2'enyl~-7-hydroxycoumarin, and
8-(2'-bromo-1',5'dimethylhex-2'enyl)-7-hydroxy-6-
octadecylcoumarin.
Representative examples of compounds V (flow diagram)
~hich can be made by cyclization from the examples of compounds
III listed in the foregoing are:
4,5',8-trimethylpsoralen,
5'-methyl-8-methoxypsoralen,
4'-ethyl-4,5',8-trimethylpsoralen,
5'-ethyl-3,4,4'5-tetramethyl-8-propylpsoralen,
5',8-dimethyl~soralen, and
4'-heptyl-8-methoxy-5'-methylpsoralen..
Representative examples of compounds VI (flow diagram)
which can be made by cyclization from the examples of
compounds IV listed in the foregoing are:
4,5'-dimethylisopsoralen,
5'-methylisopsoralen,
5'-propylisopsoralen, and
5'-isopentyl-6-octadecyl-4'-methylisopsoralen.
The solvent employed for the reaction is not critical;
in fact, a fusion process may be used if desired. An acid-
binding agent, e.g., a hydrogen halide acceptor, is generally
TC-ELD~R-5
~ 163642
employed in the cyclization step of the invention, i.e ,
Compound III -~ V or IV -~ VI. The solvent in said
cyclization reaction preferably comprises or consists of a
tertiary amine which is itself a hydrogen halide acceptor.
Preferred such tertiary amines are N,N-diloweralkylanilines.
The temperature of heating is not critical but should not
be so high as to produce undesirable side effects or so low
that the reaction proceeds at an uneconomically slow rate.
Solvents having boiling points of 190C or higher are therefore
preferred, and the boiling points of such solvents are gen-
erally satisfactory for carrying out the reaction. Atmos-
pheric pressure is ordinarily employed, but increased pressures
may be used to permit efficient use of lower-boiling solvents.
Likewise, reduced pressures may be employed to permit
efficient use of higher-boiling solvents, all as will be
apparent to one skilled in the art.
Representative solvents for Step 1 (II ~ III or IV
(flow diagram1 are as follows:
a. No solvent is required. Many Claisen rearranqements
carried out without a solvent, i.e., by simply
heating a compound of Formula II at ca. 200C,
(at which temperature it melts).
b. decalin
c. fluorene
d. diphenyl ether
e. diethyleneglycol monoethyl ether
f. ethyl benzoate
q. butyl ether
h. l,2,4-trichlorobenzene
i. p-tolunitrile
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1 1 63B~2
In general, any conventional organic solvent which is
non-reactive with the reactants and reaction products under
conditions of the reaction may be employed, when a solvent is
utilized, as will be apparent to one skilled in the art.
Representative acid-binding agents for Step 2
(III -~ V or IV -~ VI (flow diagram) are as follows:
A. Representative solids which can be used in conjunction
with solvents a through d above are:
a. potassium or sodium carbonate
b. calcium oxide
c. barium hydroxide
d. potassium or sodium bicarbonate
e. potassium or sodium acetate
B. Representative basic solvents which can be substituted
for or used in conjunction with those solvents a
through d in the foregoing are as follows:
a. N,N-dimethylaniline
b. N,N-diethylaniline (or other N,N-diloweralkylaniline)
c. p-toluidine
d. collidine
e. tributylamine
f. N,N-dimethylmesidine
g. morpholine
h. 2,4-lutidine
1. qulnollne
j. methylpiperazine
k. methylpiperidine
Basic solvents of this type are especially preferred
when it is deslred to proceed directly from Compound II
_g _
TC-ELDER-5
~ 1 63B~
to Compound V or from Compound II to Compound VI without
isolation of an intermediate.
DETAILED DESCRIPTION OF THE INVENTION
The following Preparations and Examples are given by
way of illustration only, and are not to be co~strued as
limiting.
EXAMPLE I: Preparation of 4,5',8-Trimethylpsoralene
Part l-A: 4,8-Dimethyl-7-(2'bromoallyloxy~coumarin
A mixture of 4,8-dimethyl-7-hydroxycoumarin (2.00g.,
10.5 m mole), anhydrous potassium carbonate (2.9g., 21 m mole),
freshly-distilled 2,3-dibromopropene (2.50 g., 12.6 m mole,
b.p. 42-44C/ll torr~, and acetone (75 ml.) was stirred and
heated under reflux for six hours. Inorganic salts were filtered
from the cooled solution and washed with acetone. Evaporation
of the combined filtrate and washingunder reduced pressure
left a nearly colorless residue (3.52 g., m.p. 128.5-131C) of
4,8-dimethyl-7-(2'-bromoallyloxy)coumarin, that smelled faintly
of 2,3-dibromopropene. Recrystallization of a sample (1.00 g.)
from methanol gave colorless needles (0.84 g., 91~ yield) of
m.p. 130-132C. Another recrystallization gave an analytical
sample of m.p. 131-131.5C.
Anal. Calcd. for C~4H1303Br: C, 54.39; H, 4.24; Br, 25.85.
Found: C, 54.32; H, 4.24; Br, 26.07.
Part l-B: 4,5',8-Trimethylpsoralene
A mixture of 4,8-dimethyl-7-(2~bromoallyloxy)coumarin
(200 mg., 0.65 m mole, m.p. 130-132C) and freshly-distilled
N,N-diethylaniline (5.0 ml.) was stirred under a nitrogen
atmosphere and heated under reflux for twenty-four hours at
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1 1 63642
an oil bath temperature of 22S+ 2C. An ether solution of
the dark-brown reaction mixture was filtered, and the filtrate
was washed with several portions of 5% aq. sodium hydroxide
and one portion of 6M hydrochloric acid. After drying (MgSO4),
the ether solution was concentrated under reduced pressure to
a tan residue (131 mg., 88~ yield, m. p. 222-228C). Recrystal-
lization of 120 mg. from 95% ethanol gave 4,5',8-trimethyl-
psoralene as fine needles (82 mg., 60% yield) of m.p. 232.5-
233.5C (rptd.: m.p. 234C). The melting point of a commercial
sample was 230-232C when determined simultaneously. The
infrared spectra of the two samples were identical.
EXAMPLE II Preparation of 4,5',8-Trimethylpsoralene
Part 2-A: 4,8-Dimethyl-7-(2Lchloroallyloxy)coumarin
A mixture of 4,8-dimethyl-7-hydroxycoumarin (8.00 g.,
42.1 m mole); anhydrous potassium carbonate (18.1 g., 130 m
mole); 2,3-dichloropropene (33.6 g., 302 m mole); and acetone
(600 ml.) was stirred and heated under reflux for twenty-four
hours. The reaction mixture was concentrated to ca. 200 ml~.,
filtered, and the inorganic salts were washed with acetone.
Evaporation of the combined filtrate and wash~ng under reduced
pressure left a tan-colored residue (11.30 g.). Recrystal-
lization from aqueous methanol gave a 77% yield of 4,8-dimethyl-
-7-(2Lchloroallyloxy)coumarin as small, off-white needles
(8.55 g., m.p. 117.5-120C). Another recrystallization did
not change the m.p. but gave an analytical sample.
Anal. Calcd. for Cl4HI3O3Cl: C, 63.52; H, 4.95; Cl, 13.39.
Found: C, 63.39; H, 5.12; Cl, 13.52.
:;~
~ ~ Part 2-B: 4,5',8-Trimethylpsoralene
:
~ A mixture of 4,8-dimethyl-7-(2'chloroallyloxy)coumarin
. . , _
,:
::
TC-ELDER-5
I ~ ~3642
(500mg., 1.89 m mole) and NIN-diethylaniline (5.0 ml) was
protected by an "Aquasorb" (TM), brand of phosphorous
pentoxide drying tube, while being heated under reflux
for twenty-four hours at an oil bath temperature of 220-
225C~ Treatment of the reaction mixture as described
in part l-B gave some black, ether-insoluble material which
was discarded. The desired 4,5',8-trimethylpsoralene was
obtained as a tan solid (154 mg., 41.6% yield), which was re-
crystallized from 95% ethanol to obtain light tan needles
(53 mg., 14% yield) of m.p. 233C (rptd m.p. 234C). Its
infrared spectrum was identical to that of a commercial sample.
EXAMPLE III-Preparation of
4,8-Dimethyl-6-(2'bromoallyl)-7-hydroxycoumarin
A mixture of 4,8-dimethyl-7-(2'bromoallyloxy)coumarin
(1.00 g., 3.24 m mole) and freshly distilled N,N-diethylaniline
(5.0 ml.) was protected by an "Aquasorb" (TM) tube while being
stirred and heated under reflux for three hours at an oil bath
temperature of 225+ 3C. An ether solution of the dark brown
reaction mixture was filtered to remove a black solid (ca. 10 mg.),
extracted with several portions of 5% aqueous sodium hydroxide,
washed several times with 6M hydrochloric acid, dried (MgSO4j,
and concentrated to a tan solid (0.43 g., m.p. 114-125C) which
was probably impure starting material. The alkaline extracts
were acidified with ooncentrated hydrochloric acid toobtain 4,8-di-
methyl-6-(2~bromoallyl)-7-hydroxycoumarin as an off-white
solid (0.53g., 53% yield, m.p. 154-161C) that was collected
by ether extraction. Recrystallization from aqueous ethanol,
followed by another recrystallization from benzene, gave an
analytical sample of m.p. 175-176C.
. . . .~ . : ,. . .. .
~ ~ -12-
:~:
TC-ELDER 5
1 1 ~3642
Anal. Calcd. for C~4Hl303Br: C, 54.39; H, 4.24; Br, 25.85.
Found: C, 54.83; H, 4.39; Br, 25.$7
Heating the 4,8-dimethyl-6-(2'bromoallyl)-7-hydroxycoumarin
in the presence of a hydrogen halide acceptor, for example,
N,N-dimethylaniline or sym-collidine, converts it to 4,5',
8-trimethylpsoralene.
EXAMPLE IV-Preparation of
4,8-Dimethyl-6-t2'chloroallyl)-7-hydroxycoumarin
A mixture of 4,8-dimethyl-7-(2'chloroallyloxy)coumarin
(500 mg., 1.89 m mole ) and N,N-diethylaniline (5.0 ml.) was
protected by an "Aquasorb" (TM) tube while refluxing for nine-
teen hours at an oil bath temperature of 220-225C. The cooled
mixture was treated as described in Example III to obtain
4,8-dimethyl-6-(2~chloroallyl)-7-hydroxycoumarin as a tan
solid (307 mg., 61~ yield, m.p. 135-163C) from the acidified
alkaline extracts. Recrystallization from benzene using
active carbon gave small yellow needles (183 mg., 37~ yield,
m.p. 172-176C).
Anal. Calcd. for Cl4HI3O3Cl: C, 63.52; H, 4.95; Cl, 13.39.
Found: C, 63.62; H, 4.75; Cl, 13.42.
Heating the 4,8-dimethyl-6-(2'-chloroallyl)-7-hydroxycoumarin
in the presence of a hydrogen halide acceptor, for example,
N,N-dimethylaniline or sym-collidine, converts it to 4,5',
8-trimethylpsoralene.
EXAMPLE V-Preparation of 4,5'-Dimethylisopsoralene
Part l-A: 4-Methyl-7-(2'bromoallyloxy)coumarin
4-Me~hyl-7-hydroxycoumarin (2.00 g., 11.4 m mole) was
refluxed with freshly-distilled 2,3-dibromopropene 12.72 g.,
13.6 m mole), anhydrous potassium carbonate ~3.15 g., 22.8 m
mole), and acetone (80 ml.) for four hours. The reaction
... .. . . . . .. .
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:
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1 3 63642
mixture was treated as described for the preparation of
Example I, Par' l-A to obtain 4-methyl-7-(2~bromoallyloxy)
coumarin as an off-white solid (3.70 g.) that contained some
excess 2,3-dibromopropene. Recrystallization of a portion
(500 mg.) from ligroin (b.p. 100-120C) gave needles (394 mg.,
89% yield) of m.p. 109.5-110.5C. An analytical sample of
m.p. llO-111C was obtained by recrystallization from methanol.
~nal. Calcd. for C~3HllO3Br: C, 52.97; H,3.7S; Br, 27.08.
Found: C, 52.98; H, 3.80; Br, 27.18.
Part l-B: 4,5'-Dimethylisopsoralene
Rearrangement and cyclization of 4-methyl-7-(2'bromo-
allyloxy)coumarin (500 mg., 1.69 m mole) was carried out as
described in Example I, Part l-B, except that N,N-dimethyl-
aniline (12.5 ml.) was used instead of the diethyl homolog.
The same purification procedure gave 4,5'-dimethylisopsora-
lene as a tan solid (289 mg., 80% yield) of m.p. 173-179.5C.
Recrystallization from methanol using active carbon afforded
light tan needles (161 mg., 45% yield) of m.p. 182.5-184C
(rptd.: m.p. 182-183C). The infrared spectra of this
sample and that of an authentic sample were identical.
EXAMPLE VI-Preparation of
4-Methyl-8-(2'bromoallyl)-7-hydroxycoumarin
A mixture of 4-methyl-7-(2'-bromoallyloxy)coumarin
(S00 mg.) and freshly-distilled N,N-diethylaniline (12.5 ml.)
was stirred under a nitrogen atmosphere and heated under
reflux for five hours at an oil bath temperature of ca. 225C.
An ether solution of the reaction mixture was extracted with
several portions of 5% aqueous sodium hydroxide, which were
acidified and re-extracted with ether to obtain 4-methyl- _
_
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TC-ELDER-5
~ 1 63642
-8-(2~bromoallyl)-7-hydroxycoumarin as an off-white solid
(206 m~). Recrystallization from 95~ ethanol gave fine,
off-white needles (102 mg., 20% yield) of m.p. 2Ql-202C.
Another recrystallization gave an analytical sample of
m.p. 204.5-205C.
Anal. Calcd. for Cl3HllO3Br: C, 52.97; H, 3.75; Br, 27.08
Found: C, 52.97; H, 3.75; Br, 26.56.
Heating the 4-methyl-8-(2Lbromoallyl)-7-hydroxycoumarin
in the presence of a hydrogen halide acceptor, for example,
N,N-dimethylaniline or sym-collidine, converts it to 4,5~-
dimethylisopsoralene.
ExAMæLEs VII THROUGH XVI-Additional Preparations
In the same manner as given in the foregoing examples,
by the reaction of starting compounds having Formula I with
selected 1,2-dihaloloweralkenes, additional compounds having
Formula II are produced and converted to end products having
Formulas V and VI, preferably without isolation of the inter-
mediate compounds of Formulas III and IV, respectively, all
according to the reaction sequence fully set forth on page 4
hereof and employing, as starting materials of Formula I,
those compounds set forth on page 5 hereof; as reactant 1,2-
dihaloloweralkenes, those compounds set forth on pages 5 and 6
~ .
hereof; thus to prepare compounds of Formula II as set forth
on page 6 hereof, as well as compounds of Formula III as set
forth on pages 6 and 7 hereof, and compounds of Formula IV as
set forth on page 7 hereof, which latter type of compounds of
,:
Formulas III and IV are preferably not isolated, but converted
directly in situ, according to the foregoing examples, to the
end products being compounds of Formulas V and VI, also as set
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.
`
TC-ELDER-5
1 3 63642
forth on page 7 hereof. The procedure employed is substantially
as set forth in the foregoing examples, as well as reaction
conditions and work-up for procurement of the final end products
in each case. The end products in each case are the compounds
of Formulas V and VI set forth on page 7 hereof.
As used herein, loweralkyl means such radicals con-
taining up to and including eight carbon atoms, such as methyl,
ethyl, propyl, butyl, amyl, hexyl, heptyl and octyl, and
loweralkoxy means such radicals of the formula -O-loweral~yl.
It is to be understood that the invention is not to be
limited to the exact details of operation or structure shown
and described, as obvious modifications and equivalents will
be apparent to one skilled in the art.
,
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,
