J. Chem. Sot. (C), 1970
2 3 2 4
Preparation and Absolute Configuration of the Enantiomeric 3,4-Dihydro-
4-methylcoumarins
By J. Grimshaw” and P. 6. Pillar, Department of Chemistry, Queen’s University, Belfast BT9 5AG
(-t-)-(I?)-3,4-d{-
Enantiomers of 3-phenylbutyric acid have been converted into 3,4-dihydro-4-methylcoumarin.
hydro-4-methylcoumarin has [alD20 +35” (c 1 in benzene).
optically active a m in es [cin ch on in e, codein e, yoh im bin e,
spartein e, an d (-)-1-ph en yleth ylam in e] were dissolved in
a qu eou s eth a n ol. K‘o crystallin e salts cou ld be obtain ed.
(-j-)-(S )- a n d (-)-(R)-3-Phenylbztty~ic Acid.--S-Ph en yl-
T HE value of the specific rotation of 3,4-dihydro-
4-methylcoumarin was required for comparison with
the results described in the preceding paper.l Some
attempts were made to resolve 3-(o-methoxyphenylj-
butyric acid, which could then be demethylated to give
the dihydrocoumarin, but no crystalline salt of the
acid with an optically active amine could be obtained.
Enantiomers of the dihydrocoumarin were eventually
bu tyric was resolved by u se of (
am in es.l Th e dia stereoisom eric sa lts crystallised
a qu eou s eth a n ol a n d th e recovered a cids h a d th e followin g
p r o p e r t ie s : (+)- (S )- a c id [a],2o +-52” (c in b e n z e n e ),
[a],,“” - 5 1 ” (c i n b e n z e n e ) {lit.,’ [a],2o
)- an d (
)-l-ph en yleth yl-
from
1
(-)-@)-acid
1
prepared from active 3-phenylbutyric
acid. Resolution
-57.2 (G 9 in ben zen e), [a],“” -5S.5 (c 2 in benzene)).
3-Mcthylindan- I-one .-3-Ph en ylbu tyric
acid (10 g.) an d
of 3-phenylbutyric acid
2
proceeds readily on crystall-
polyph osph oric acid (29 g.) were m ixed at 50” an d kept at
95” for 90 m in.; th e colou r ch an ged from yellow to red.
Th e m ixtu re wa s th en pou red on cru sh ed ice (ca . 40 g.)
an d tritu rated u n til th e polyph osph oric acid h ad decom -
posed. Th e orga n ic produ ct wa s extra cted with ben zen e,
wash ed with dilu te sodiu m h ydroxide an d water, dried
isation of its salts with active 1-phenylethylamine.
The absolute configuration of (-)-(RR)-3-phenylbutyric
acid
3
(I) has been determined by relating this acid
chemically to (+)-(S)-hydratropic acid. The S-phenyl-
butyric acid was converted into 3-methylindan-l-one,
which afforded 3,4-dihydro+methylcoumarin
oxidation with peroxy-acid.
Weidler and Bergson
a ft er
an d
evaporated.
Distillation of th e residu e
(6.4 g. , 72%), b . p . 116-
WEm*)
)
a
a ffo r d e d 3-m eth ylin da n -l-on e
llS”/lO m m . (lit.,
b u t yr ic a c id ga ve (S)-3-m eth ylin da n -l-on e,
(c in b en zen e) a n d
ph en ylbu tyric
[a],“0 +2*0” (c 1 in ben zen e) a n d
4
have prepared both enantiomers
4
112-113”/9 m m . ). (+)-(S)-S-Ph en yl-
[a],“0 l-4”
in aceton e); (-)-(R)-3-
of 3-m et h ylin da n -l-on e fr om t h e a ct ive 3-phenylbutyric
acids by treating the acid chlorides with aluminium
1
j-16” (c
2
a c i d g a v e (K)-3-m eth ylin dan -l-on e
(I I )
chloride in dry benzene.
However, Eliel and his co-
have shown that active 2-phenylbutane is
-
20” (c 1 in a ceton e),
workers
2
broad n egative c.d. with at least th ree partially resolved
rapidly racemised by aluminium chloride at 0”. We
therefore employed warm polyphosphoric acid to cyclise
peaks, &,. 350 (AE -0*495), 340 (-l-05), an d 325 n m .
- 1 . 1 1 ) .
(AC
the 3-phenylbutyric
acid.
5
To ensure that racemisation
Enantiomers of 3,4-Dihy&o-4-methylcownavin.-3-Methyl-
in da n -l-on e (1.5 g., 0.01~) an d peroxylau ric acid (4.3 g.,
0.0211) in dich lorom eth an e (25 m l.) con tain in g m eth a n e-
su lph on ic acid (1 g.) were h ea ted u n der reflu x in th e dark
for 24 h . Th e m ixtu re wa s th en gen tly swirled with a n
excess of cold dilu te sodiu m h ydroxide solu tion , an d th e
dich lorom eth an e layer was wash ed with dilu te h ydro-
ch loric acid an d water, dried (MgSO,), an d evaporated.
Th e residu e wa s distilled to yield 3,4-dih ydro-4-m eth yl-
cou m arin , b.p. S7-90’/0*1 mm. (1.6 g., SO%), wh ose pu rity
was not taking place under these conditions the c.d.
in dioxan, was measured
of (R)-3-methylindan-l-one,
after treatment with polyphosphoric acid under the
same conditions as used in the cyclisation reaction.
Comparison with the c.d. measured before this treatment
showed no significant difference.
w a s d e t e r m in e d b y g.1.c. an alysis [Perkin -Elm er Fl
1
in stru m en t; flu orosilicon e oil colu m n (2 m .)
;
tem p. 130’1.
Th e prin cipa l im pu rity wa s u n ch a n ged m eth ylin da n on e a n d a
calibration graph was m ade for m eth ylin dan on e-dih ydro-
m eth ylcou m arin m ixtu res. (R)-3-lMeth ylin dan -l-on e ga ve a
(1) (-I-(W
PI) (+)-P)
(III) (+f-w
Sign of rotation for solu tion in ben zen e at 589 n m .
m ixtu re with [a],“O
+24” (c
1
i n b e n z e n e ) o f dih ydro-
cou m a rin (75%) a n d in da n on e (25%). Th u s th e pu re
(+)-(R)-3,4-dih ydro-4-m eth ylcou m arin
The preparation of 3,4-dihydrocoumarin
of indan-l-one with peroxy-acids has been reported.6
by oxidation
( I I I ) h a d [a],“”
+
32” (c
1 in benzene).
EXPERIMENTAL
(S)-3-Meth ylin da n -l-on e
g a ve
a
m ix t u r e [a],“”
2 3 ”
(c
1 in ben zen e) of dih ydrocou m arin (7 6 %) a n d in da n on e
Attempted Resolution of 3-(o-Methoxyphenyl)butyriG
Acid.
(2 4 % ). Th u s (-)-(S)-3,4-dih ydro-4-m eth ylcou m arin
h a d
-Equ im olar qu an tities of th e acid an d each of several
[a],“” -30” (c 1 in b en zen e).
l
R. N. Gou rley,
J . Grim sh aw, an d P. G. Millar, precedin g
p a p er .
2
E. L. Eliel, P. H. Wilken , an d F. T. Fan g, J . Org. Chem.,
5
H. R. Sn yder an d F. X. Werber, J . Anzer. Chem. SOL, 1950,
1957, 22, 231.
72, 2965.
3
V. Prelog an d H. Sch errer, H&v. Chim. Acta, 1 9 5 9 , 4 2 ,
6
M. Clerc-Bory an d C. Men tzer, Camp. rend., 1955, 241,
2 2 2 7 .
1316.
A. M. Weid ler an d G. Bergson , Acta Ch a m . &an d., 1964,
18,4 1 4 8 4 .
’ H. Ru pe, Annalen, 1 9 0 9 , 369, 325; D. J . Cram, J . Amer,
C h em . SOL, 1952, 74, 2 1 3 8 .
Grimshaw
