Schmidt Reaction of E-3-Benzylidenechromanones and E-3-Benzylidenethiochromanones

On treatment with NaN 3 /c. H 2 SO 4 -HOAc or NaN 3 /TFA, E-3-benzylidenechromanones are mostly converted to E-βaminobenzylidenechromanones while E-3-benzylidenethiochromanones are converted to 3-benzoylthiochromones. A structurally new type of product has been isolated for the reaction of E-3-benzylidene-4-methoxychromanone with NaN 3 /TFA. Mechanistic paths have been suggested for formation of the products.


Introduction
The Schmidt reaction [1] is an organic reaction involving alkyl/aryl migration over the carbon-nitrogen bond in an azide with expulsion of nitrogen.A key reagent introducing this azide group is hydrazoic acid, and the reaction product(s) depends on the nature of the substrate.Moreover, there are important variants of this reaction, developed mainly by Aubé et al. [2,3], which include rearrangements through interactions of carbocations and alkyl azides or carbonyl compounds and alkyl azides, either intermolecularly or intramolecularly.Schmidt reaction of chromanones and their analogues has been studied by a number of groups [4][5][6][7][8][9][10][11][12][13].Schmidt reaction of E-3-benzylideneflavanones (1) (Figure 1), done by us, produced some novel results [14][15][16].In continuation of that work, we undertook the study of Schmidt reaction of E-3-benzylidenechromanones (2) and E-3-benzylidenethiochromanones (3).As in the case of 1, the reaction was performed under the two reaction conditions for these substrates also.The results obtained in this study are presented herein.

Results and Discussion
When the E-3-benzylidenechromanones 2a-h and the E-3-benzylidenethiochromanones 3a-c were treated with NaN 3 /c.H 2 SO 4 -HOAc at room temperature, none of them underwent significant change even after 24 h.On heating the reaction mixture at 60 ∘ C, the starting materials gradually changed to products, and the reactions were complete within 12 h (subsequently this temperature was found to be the optimum temperature for the reaction).Chromatography of the resulting crude materials obtained after work-up gave pure crystalline products in moderate yield from the reactions of 2a-f and 3a-b.From the reactions of 2g-h and 3c, any pure product could not be isolated.Characterization of the products from their spectral data showed that 2a-f gave E--amino-3-benzylidene-4-chromanones (4a-f) whereas 3ab gave E-3-benzoylthiochromones (5a-b) (Scheme 1, Table 1).
The products obtained from 2a-f were assigned Econfiguration, as both the protons of their NH 2 group appeared at the same field in their 1 H NMR spectra.If the configuration was Z, these two N-H protons would have appeared at two different positions due to intramolecular hydrogen bonding of only one of them with >C=O [15,16].
When the E-3-benzylidenechromanones 2a-b and 2g were treated with NaN 3 (1 : 1.5 mole ratio) in TFA and the mixture was kept for 4 days at room temperature, the first two substrates gave E--amino-3benzylidenechromanones (4a-b) while the last one gave another type of product (6).Under the same reaction condition, E-3-benzylidenethiochromanone (3a), however,  gave 3-benzoylthiochromone (5a) (Table 2).Configuration of the product 6 could not be settled so far.Suggested mechanisms for formation of 4 and 6 are given in Schemes 3 and 4, respectively.For formation of 5, the first step will be similar to the first step shown in Scheme 3. The resulting intermediate 7 (Figure 2) then follows a different path promoted by sulphur leading to 5. At this stage, no suggestion is being made about the nature of the path.
It is noteworthy that disposition of the NH 2 group in 4 is opposite to that of an analogous product from 1 [15,16], though they are formed under similar reaction conditions.The absence of a 2-aryl group in 2 is possibly responsible for this difference.Regarding the formation of 6 in one case only, it may be mentioned that the conjugation of OMe with C=O in the intermediate 4g possibly makes it more reactive to undergo the reaction shown in Scheme 4.

Conclusions
We report here transformation of E-3-benzylidenechromanones ( 2) and E-3-benzylidenethiochromanones (3) to products of the types 4-6 by Schmidt reaction under two experimental conditions, which follow interesting mechanistic paths.

Experimental Section
Melting points were recorded on a Köfler block.IR spectra were recorded on a Perkin Elmer FT-IR spectrophotometer (Spectrum BX II) in KBr pellets. 1 H and 13 C NMR spectra were recorded in CDCl 3 on a Bruker AV-300 (300 MHz) spectrometer.Analytical samples were routinely dried in vacuo at room temperature.Microanalytical data were recorded on two Perkin-Elmer 2400 Series II C, H, and N analyzers.Mass spectra were measured in the following ways: ESIMS(+) (Waters Micromass Q-Tof micro) and FAB-MS (Jeol the M Station JMS.700).Column chromatography was performed with silica gel (100-200 mesh), and TLC with silica gel G made of SRL Pvt. Ltd.Petroleum ether had the boiling range 60-80 ∘ C.

General Procedure for the Reaction of E-3-Benzylidenechromanones (2) and E-3-Benzylidenethiochromanones (3) under Schmidt Reaction Conditions
Condition I.An appropriate E-3-benzylidenechromanone (2)/E-3-benzylidenethiochromanone (3) (1 mmol) was dissolved in .H 2 SO 4 -HOAc mixture (1 : 5, 6 mL) and to the solution sodium azide (1.5 mmol) was added in three portions at 5-minutes interval with stirring.The solution was heated at 60 ∘ C and the stirring was continued for 12 h and then diluted with water (150 mL).The resulting mixture was extracted with chloroform (2 × 25 mL) and the extract was dried over anhydrous sodium sulphate.The concentrate of the chloroform extract was chromatographed over silica gel using petroleum ether-ethyl acetate mixtures of increasing polarity as eluents to get pure products.
Condition II.An appropriate E-3-benzylidenechromanone (2)/E-3-benzylidenethiochromanone (3) (1 mmol) was dissolved in TFA (3 mL) at 5 ∘ C and to the cold solution sodium azide (1.5 mmol) was added in three portions at 5-minute intervals.The resulting mixture was kept at room temperature for 4 days and then diluted with water (150 mL).The resulting mixture was extracted with ether (3 × 35 mL) and the extract was dried over anhydrous sodium sulphate.The concentrate of the ether extract was chromatographed over silica gel using petroleum ether-ethyl acetate mixtures of increasing polarity as eluents to get pure products.The products of the above reactions were characterized from their analytical and spectral data as given below.