Synthesis of Coumarins and 4-Hydroxyquinolinones
SCHEME 1. Synthesis of Coumarins
of the Reformatsky reaction by treatment of R-halocar-
bonyl and related compounds with tellurides usually
resulted in the protonation of the enolate or the elimina-
tion of ketene;30 but intermolecular reactions with alde-
hydes31 and ketones32 have been observed. Cyclopropan-
alogues of R-haloketones undergo similar reactions with
telluride ions.33 An initial attempt to prepare coumarin
by intramolecular cyclization of the bromoacetate ester
of salicylaldehyde triggered by sodium telluride failed.30g
No other telluride-induced attempted cyclization appears
to have been reported.
TABLE 1. Solvent Effects on Yields of Coumarin 3a via
Sodium or Lithium Telluride
Coumarins (2H-1-benzopyran-2-ones) have been pre-
pared by a number of methods involving formation of a
3-4 carbon-carbon bond.34 For example, the Kosta-
necki-Robinson reaction of o-hydroxyarylalkyl ketones
with an acid anhydride and the sodium salt of an acid
produces coumarins by formation of the 3-4 carbon-
carbon bond via the ester enolate, but chromones (4H-
1-benzopyran-4-ones) can be the major products via the
ketone enolate, and yields can be variable.35,36 A method
(Claisen) that avoids the chromone byproducts of the
Kostanecki-Robinson reaction is the treatment of methyl
time,
h
coumarin,
%
tracea
11-23
46
entry
solvent
T, °C
telluride
1
2
3
4
5
DMF
THF
-20 to rt
2
Na2Te
Na2Te
Na2Te
Na2Te
Li2Te
-20 to rt 16
benzene-THF (19:1) 6 to rt
ether-THF (9:1)
16
-20 to rt 24
-78 to rtb
1.5
45
75
THF
a Reference 30g: salicylaldehyde, 8%; salicylaldehyde dimeric
acetal, 32%. This result is explained by the authors via presumed
ketene formation. b Allowing the reaction in THF to proceed at
-78 °C for 1 h with quick warming (5-10 min) to room temper-
ature and further standing for 30 min gave the best results.
esters of 2-alkanoyloxybenzoic acids with metallic
sodium37a,b or with bases.37c-f Coumarins also have been
prepared in good yields by a ring-closing metathesis
reaction (3-4 bond formation),38 but this reaction is not
ideal with respect to carbon atom economy and requires
a ruthenium catalyst.
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Results and Discussion
Synthesis of Coumarins and 4-Hydroxycoumarins.
We have achieved the previously unsuccessful sodium
telluride-triggered cyclization of the bromoacetate of
salicylaldehyde to coumarin (yields 11-75%) (Table 1).
The cyclization proceeds by formation of the phenolate
ester enolate, elemental tellurium, and bromide ion. The
enolate anion either attacks the ortho carbonyl group
leading to cyclization or eliminates a phenolate ion to give
a ketene.
The yield of coumarin depends on reaction conditions
and the workup. When sodium telluride is the reagent,
the yield is improved by use of solvents (THF, ether-
THF, benzene-THF) less polar than the DMF of the
earlier failed attempt30g (Table 1, entries 1-4).
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