The 3-Acyl-2-R-methylchromones as several functional compounds are useful building-blocks in organic synthesis. The chromones are attractive for ability to form of new nitrogen heterocycles after nucleophilic opening of -pyrone ring [1,2]. Methyl groups at position 2 and at carbonyl group of study compounds can be active in aldol type reactions. Carbonyl groups and carbon at position 2 as electronodeficit centers are very effective in reactions with nucleophile reagents. Synthesized compounds 2-6 are useful for are ability to transform in different ways and at versatile steps of the synthetic sequence. For this work we have chosen some method for preparation of compounds 2-4. As we showed before [6,7]. microwave irradiation is a suitable method for condensation reactions.
Results and Discussion
The main goal of the study was the preparation of new
3-acyl-2-R-methylchromones and comparison of the reactions results obtained by
classic method and microwave irradiation. Structural formules of prepared
compounds are depicted in scheme.
For preparation of compounds 2 are known two methods. One of them is
Kostanecki-Robinson acetylation of 2-hydroxyacetophenone derivatives with
acetic anhydride and sodium acetate [3]. This cyclocondensation reaction is
known yet only in a classic modification by heating of react mixture. The
another more general method of preparation of 3-acyl-2-methylchromones , can
be used the rearrangement of 2-acyloxy-1-acetoarones after treating
with metallic sodium. Rearranged intermediates - 2-hydroxyaroylacetones
1 were formed. They afforded of 3-acyl-2-methylchromones or
2-methylchromones by acid-catalyzed cyclization.
In our study is reported preparation of the 3-acetyl-2-methylchromone
derivatives 2 in good yield (72 - 98 %) by treating under classic
reaction conditions of 2-hydroxy- aroyl acetone derivati-ves 1 with
freshly fused sodium acetate and acetic anhydride to give the desired products
2 after 2 hours refluxing. The using microwave irradiation products
2 were prepared from the same compo-nents, but react time was shortened
to 3 - 8 minutes.
The structure of compounds 2( R=H) were confirmed by IR,
1H-NMR, and 13C-NMR spectra. IR-spectra (in nujol) showed an
acetyl carbonyl stretching frequencies as strong band at 1699 -1677
cm-1 and - pyrone at 1648 - 1636 cm-1. In the
1H-NMR spectra of the CH3 acetyl signals occurred at
2.70 - 2.62 ppm, on the other hand the signals of CH2-CH3
occurred at 2.66 - 2.52 ppm , other protone signals and the
13C-NMR spectra are listing in Experimental Part.
3-Benzoyl-2-methylchromone derivatives 2(R=C6H5)
were prepared by treatment of 2-hydro-xybenzoylacetophenones with acetic
anhydride and sodium acetate at 110o C for 3 hours. On the other
hand by focused microwave irradiation yield 80 % were produced after 6 minutes
.
The preparation of compounds 3 and 4 imagines a new route to
synthesis of the title compounds. Reaction of compounds 1
with acid chlorides and potassium carbonate in acetone
reflux for 3 hours yielded 3-acetyl-2-aryloxymethylchromone derivatives
3 in about 47 % yields. Intermediates 4
were isolated from cold water hydrogen carbonate solution after acidification
with CH3COOH in about 30 % yields. The cyclocondensation of
intermediates 4 on compounds 3 is very easy
by heating in benzene medium.. The heating of starting compounds 1
in refluxing (dry toluene 3 hs.) were isolated only cyclic products
3 (in 80% yields). In the microwave oven the condensation
reaction of components 1 with acylchlorides, potassium carbonate
and acetone required only 2 minutes time for 85 % yield of compounds 3.
No any intermediates 4 there were isolated.
Compounds 2 contain two active CH3 groups which can react
at aldol reaction. Aldol conden-sation product 6 was obtained by
reaction 2 with 3-formyl chromones in acetylanhydride medium by
classic and also microwave irradiation methods respectively. In every attempts
, the reaction was realized only at 2-position-methyl group of -pyrone ring
.The classic arrangement of method required 2h of react time. Beneficial effect
of microwave irradiation on the reaction shortened the react time into 40
sec.
It is known that reaction of 3-acetyl-2,6-dimethylchromone with hydroxylamine
in acetic acid gave monoxime and dioxime [4], but reaction of
3-acetyl-2-methyl-chromone with hydroxylamine hydrochloride and sodium acetate
in ethanol gave 4-acetyl-5-(2-hydroxyphenyl)-3-methylisoxazole [5].