Synthetic model of a new deoxybenzoin derivative from Deguelia hatschbachii A

In this paper we describe the synthesis of 2 ́,4 ́-dimethoxy-8-(propyl-2-one)-deoxybenzoin, a new compound employed as a model for the comparison with the respective spectral data for 6’,4dihydroxy-3’-(3,3dimethylallyl)-2",2"-dimethylchromene(5",6":5’,4’)-2’-methoxy-8-(propyl-2-one) deoxybenzoin, recently isolated from Deguelia hatschbachii A.M.G. Azevedo. Both compounds have a “propyl-2-one” group attached to C-8 of the deoxybenzoin skeleton, for which there is no precedent in the literature. The Friedel-Crafts reaction of 1,3-dimethoxybenzene with phenylacetyl chloride furnished 2 ́,4 ́-dimethoxydeoxybenzoin, that after reaction with allyl bromide gave 2 ́,4 ́-dimethoxy-8-(allyl)deoxybenzoin. Wacker oxidation gave the desired model compound in 15% overall yield. The corresponding spectral data reinforced the structure previously determined for the natural product.

The synthesis of a-methyl deoxybenzoins is achieved by methylation of deoxybenzoin derivatives [6].In addition, deoxybenzoins are useful starting materials for the synthesis of several natural products, such as isoflavanones, stilbenes and others [9].
Moreover, it might be mentioned that the reactivity of deoxybenzoin derivatives with regard to a-alkylation remains little explored; and until now has been restricted to the a-methylation reaction [6,9].
In this paper, we describe our results on the synthesis of the model compound 2 (Figure 1), according to Scheme 1, in order to compare its spectral data with those furnished by the natural product 1, thus reinforcing its molecular structure determination [1].In a dry two-necked round bottomed flask (25 mL), equipped with a magnetic stirrer, a moisture trap and a stopper, was added a solution of 6 (80.0 mg, 0.31 mmol) in anhydrous THF (10 mL) and NaH (37.5 mg, 1.55 mmol).The reaction was left under stirring for 3 h.A solution of allyl bromide (47.0 mL, 0.55 mmol) in anhydrous THF (5.0 mL) was then slowly added during 1.5 h.The reaction was stirred for a further 2 h.After this period, the reaction mixture was poured into a beacker containing ice, and neutralized with HCl 10% (v/v).The organic material was extracted with diethyl ether (2 x 25 mL), dried over Na 2 SO 4 , filtered and concentrated.The crude product was purified by preparative thin layer chromatography (eluant hexane:diethyl ether 1:1 v/ v), furnishing the allylated deoxybenzoin 7 (42.0mg, 0.14 mmol) as a yellowish oil in a yield of 45%. 1 H NMR spectral data (500 MHz, CDCl 3 /TMS): Table 1. 13 C NMR spectral data (125 MHz, CDCl 3 ): Table 2. EIMS (probe) 70 eV, m/z (rel.int.): Figure 3.
EIMS 70 eV, direct probe.HREIMS was performed in a VG Auto Spec-Fisions Instrument by using an eletron ionization technique at 70 eV (linked scan at 8KeV collisions with Helium).

Reagents
The already known synthetic intermediates 4 and 5 were prepared respectively from resorcinol and phenylacetic acid as described.Both of them were characterized through the respective spectral data.

Results and Discussion
By analogy with the synthesis of some deoxybenzoins [9], the Friedel-Crafts acylation (Scheme 1) of 1,3-dimethoxybenzene 4 with phenylacetyl chloride 5 gave 2',4'dimethoxydeoxybenzoin 6 as expected and confirmed by 1 H and 13 C NMR (Tables 1 and 2) and MS (Figure 3) data, where the deoxybenzoin skeleton is evidenced by the absorptions at d H 4.12 (s, 2H), d C 49.6 (CH 2 ) and a base peak at m/z 165 (100%) respectively.According to the MS spectral data of many other synthetic deoxybenzoin derivatives [7] the base peak corresponds to the cleavage of C-7/C-8 bond, the resulting fragments (a cation and a radical) are both stable.Table 1. 1 H (300* and 500 MHz) NMR spectral data for compounds 2, 6 and 7.The chemical shifts are in δ (ppm).Coupling constants (ϑ) in Hz and multiplicity are described in parentheses.Table 2. 13 C (75* and 125 MHz) NMR spectral data for compounds 2, 6 and 7.
Compound 7 revealed the presence of one multiplet at d 4.57 (1H), three multiplets at d 5.65 (1H), 2.85 (1H) and 2.35 (1H), and two one-proton doublet of doublets at d 4.95 (J= 16.8, 1.0 Hz) and 4.85 (J= 10.3, 1.0 Hz) in the 1 HNMR spectrum consistent with the presence of an allyl group on C-8, which was also confirmed in the 13  All hydrogen and carbon chemical shifts were confirmed by 2D-NMR experiments such as gCOSY, HSQC and gHMBC data (Table 4).
The comparison of the NMR spectral data furnished by the model compound 2 and the natural product 1 reinforced the structural assigment of the natural product (Table 5).

Table 4.
Observed correlation in gHMBC (long-range C-H) spectra (CDCl 3 , 11 Tesla) of 2. Table 5. Comparative analysis of the 1 H (500 MHz) and 13 C (125 MHz) NMR spectral data for compounds 1 1 and 2, in CCl 4 (*) or CDCl 3 ( # ) and TMS as internal standard.The chemical shifts are in d (ppm).Coupling constants (J) in Hz and multiplicity are described in parentheses.

Conclusions
The synthetic route was useful for the preparation of the desired model compound 2. It must be mentioned that the new deoxybenzoin derivatives 2 and 7 were prepared through a new route.
The spectral data furnished by 2 gave a strong enlighentment about the studied system, and is coherent, confirming the unusual structure previously given for the natural product 1.
The MS and 13 C NMR spectral data of 2',4'dimethoxydeoxybenzoin [6] are now given for the first time.

Table 3 .
C NMR spectrum and DEPT (90 o and 135 o ) experiments by the signals at d 57.0 (CH, C-8), 38.6 (CH 2 , C-9), 136.7 (CH, C-10) and 115.9 (CH 2 , C-11).Observed correlation in gHMBC (long-range C-H) spectra (CDCl 3 , 11 Tesla) of 7 The final step involved the oxidation of the a-allyldeoxybenzoin 7 with CuCl and PdCl 2 resulting in the formation of the target compound 2. The HREIMS revealed a molecular ion [M] + of m/z 312.1362, corresponding to C 19 H 20 O 4 (required M + 312.1361).The 1 H NMR spectrum showed three doublet of doublets at d 5.06 (J= 9.6, 4.5 Hz), 3.36 (J= 17.4, 9.6 Hz) and 2.47 (J= 17.4, 4.5 Hz), and a singlet at d 2.08 (3H) respectively, assignable to an ABX system and an acetyl methyl group.This was confirmed by the presence of a methyl carbon signal at d 29.7 and a carbonyl carbon signal at d 203.9, corresponding to an alkyl ketone, in the 13 C NMR spectrum.Other signals in the 13 C NMR spectrum were compatible and DEPT (90 o and 135 o ) experiments showed the presence of three CH 3 , one CH 2 , nine CH and six quaternary carbons.