Simple and Efficient One Step Synthesis of Functionalized Flavanones and Chalcones

Introduction

Chalcones and flavanones, originally isolated from natural sources are an outstanding class of naturally occurring bioactive compounds with a 1,3-diarylpropane skeleton belonging to the flavonoid family. Chalcones (1,3-diphenyl-2-propene-1-ones) either natural or synthetic have been reported to posses varieties of biological activities^[1] including anticancer,² antimitotic,³ antiinflammatory,⁴ antimalarial,⁵ antiangiogenic,⁶ antiinfective,^4j antimicrobial, ⁷ antioxidative,^2f-g,8 and antiproliferative⁹ activities. Similarly, flavanones (2,3-dihydro-2-phenylchromene-4-one) have also been reported to posses anticancer,¹⁰ antimicrobial,¹¹ antiproliferative,^9b anti-inflammatory,^10a cardiovascular,^10a  antimalarial,^5c,12 antiangiogenic,⁶ and hypotensive^11b activities. These compounds have attracted significant interest of chemists, biochemists and pharmacologists due to their ample range of pharmacological activities and their uses as intermediates in the synthesis and biosynthesis of various classes of bioactive compounds.

Several methods have been reported for the synthesis of 2′-hydroxychalcones¹³ and flavanones^{13a,13c,13g,14}. However, these methods are associated with several drawbacks such as long reaction time, poor yield and involvement of expensive catalysts. Furthermore, flavanones are always synthesized in two steps; in first step, 2′-hydroxychalcones are prepared via the most commonly used method, Claisen-Schmidt condensation reaction between 2-hydroxyacetophenones and benzaldehydes in the presence of aqueous alkaline bases. Second step involves subsequent cyclization of 2′-hydroxychalcones intermediate to form flavanones^13a,13c,14. Nevertheless, conversion of chalcones into flavanones never completes and gives mixture of products. Also, during 2′-hydroxychalcones synthesis either the reaction never complete to give 2′-hydroxychalcones in high yield or part of 2′-hydroxychalcones cyclised to flavanone and give mixtures of chalocone and flavanone leading to tedious and time consuming column chromatographic separations. In spite of several drawbacks associated with chalcones and flavanones synthetic methods, to date, we could not find any previous report which describes the flavanones synthesis in one step. Moreover, in the last two decades use of microwave energy for conducting organic reactions has become a very popular and emerging technique as it has several advantages over classical organic reactions such as shortening reaction times, improving yields and promoting environmental friendly (Green chemistry) new reactions.

Experimental

Melting points were determined on a Gallen Kamp melting point apparatus and are uncorrected. Panasonic Microwave with model NN-C2003S/NN-C2002W was used for conducting reactions. ¹H and ¹³C NMR spectra were recorded with a JEOL ECP-400 spectrophotometer. The NMR samples were prepared in CDCl₃ with tetramethylsilane (TMS) as an internal standard. The chemical shifts and coupling constants (J) were expressed in d and Hz, respectively. MS spectra were recorded on Shimadzu QP5050A GC/MS system. The thin layer chromatography (TLC) was carried out on pre-coated silica gel 60 F254 (0.2 mm, Merck) plates. The developed TLC plates were visualized under UV light at 254 or 365 nm.

General Procedure for the Preparation of Flavanone and Chalcone Derivatives

Synthesis of flavanone and chalcone derivatives were carried out simply by mixing the appropriate amount of 2-hydroxyacetophenone derivatives (2.69 mmol) and aromatic aldehydes (2.69 mmol) in the presence of catalytic amount of aqueous KOH in MeOH and irradiating in a microwave oven at 100 W for 2 minutes. The reaction mixture was cooled, poured into crushed ice and then conc. HCl (1 ml) was added. The mixture was left to stay at 2-3°C overnight and the separated solid was collected by filtration, washed with water and recrystallized from methanol to give the desired products.

Results and Discussion

Previously, we reported a highly efficient synthesis of imines under microwave irradiotion¹⁵ and in continuation of our interest in the synthesis of heterocyclic compounds,¹⁶ we report here a simple and efficient microwave assisted synthesis of 2′-hydroxychalcones and flavanones in one step (Scheme 1) with high yield and no side products.

Scheme 1: MW-assisted synthesis of flavanones and chalcones Click here to View scheme

 

The synthesis was carried out simply by mixing the appropriate amount of 2-hydroxyacetophenone derivatives and aromatic aldehydes in the presence of catalytic amount of aqueous KOH in MeOH and irradiating in a microwave oven at 100 W for 2 minutes to give the desired products. Two different types of compounds were obtained using the same reaction conditions; the first one is 2′-hydroxychalcones, 3a-3v, (Table 1), obtained when (i) R₃ of the 2-hydroxyacetophenones, 1, = H, and the aldehydes, 2, have any type of substituents (ii) R₃ ≠ H and there is more than one substituent on the aldehydes ring. The second type is flavanones, 4a-4j, (Table 2), obtained when R₃ ≠ H and the aromatic aldehydes have either one substituent or less.

 

Table 1: Chalcone derivatives

R1	R2	R3	R4	R5	R6	R7	R8	Product	Yielda (%)
H	H	H	H	H	H	H	H	3a	81
H	OMe	H	H	H	H	H	H	3b	84
H	H	H	OMe	H	H	H	H	3c	80
H	H	H	H	H	H	Cl	H	3d	90
H	OMe	H	H	H	H	Cl	H	3e	92
H	H	H	OMe	H	H	Cl	H	3f	81
H	H	H	H	H	OMe	OMe	OMe	3g	91
H	H	OMe	H	H	OMe	OMe	OMe	3h	89
H	H	CH3	H	H	OMe	OMe	OMe	3i	83
H	H	Cl	H	H	OMe	OMe	OMe	3j	86
Cl	H	Cl	H	H	OMe	OMe	OMe	3k	92
H	H	Br	H	H	OMe	OMe	OMe	3l	84
H	OMe	H	H	H	OMe	OMe	OMe	3m	90
H	H	H	OMe	H	OMe	OMe	OMe	3n	88
H	H	H	H	Cl	H	Cl	H	3o	82
H	H	OMe	H	Cl	H	Cl	H	3p	89
H	H	CH3	H	Cl	H	Cl	H	3q	85
H	H	Cl	H	Cl	H	Cl	H	3r	91
Cl	H	Cl	H	Cl	H	Cl	H	3s	93
H	H	Br	H	Cl	H	Cl	H	3t	80
H	OMe	H	H	Cl	H	Cl	H	3u	94
H	H	H	OMe	Cl	H	Cl	H	3v	87

 

Table 2: Flavanone derivatives

R1	R2	R3	R4	R5	R6	R7	R8	Product	Yielda (%)
H	H	Cl	H	H	H	H	H	4a	85
H	H	OMe	H	H	H	H	H	4b	81
H	H	CH3	H	H	H	H	H	4c	88
Cl	H	Cl	H	H	H	H	H	4d	94
H	H	Br	H	H	H	H	H	4e	92
H	H	Cl	H	H	H	Cl	H	4f	92
H	H	CH3	H	H	H	Cl	H	4g	90
Cl	H	Cl	H	H	H	Cl	H	4h	84
H	H	OMe	H	H	H	Cl	H	4i	88
H	H	Br	H	H	H	Cl	H	4j	89

^a Isolated yield.

This result reveals that substitution at position 5 of the 2-hydroxyacetophenones, 1, plays an important and key role in the synthesis of flavanones. When 2-hydroxyacetophenone, 1, is substituted at position 5 with OCH₃, CH₃, Cl or Br and reacted with aromatic aldehydes having either one substituent or less, it gives flavanones in one step with very good yield ranging from 81-94%. On the other hand, when position 5 of 2-hydroxyacetophenone, 1, is not substituted and reacted with any type of aromatic aldehydes, it gives chalcones with yield ranging from 80-94%. To establish the general behavior of the reaction under aforedescribed conditions, twenty two representative 2′-hydroxychalcones, 3a-3v, and ten flavanones, 4a-4j, were prepared (Tables 1 and 2) among them five chalcones, 3n, 3p, 3q, 3t and 3v and one flavanone, 4h, were found to be novel compounds.

Conclusion

In conclusion, we have developed a convenient, rapid and highly efficient one step procedure for the preparation of functionalized flavanones and chalcones under microwave irradiation. On comparing the earlier reported methods for the preparation of flavanones^13a,13c,14 with ours, it was found that this is a first report of its kind in which flavanones are being prepared in one step with very high yield.

2′-Hydroxychalcone (3a)

Yellow powder; mp 79^oC (lit.^[13h] mp 81-83^oC); ¹H and ¹³C NMR data is in agreement with Lit^[13h]. MS: m/z (%) 224 (M⁺, 100), 147, 121, 103, 89, 77, 65, 51.

2′-Hydroxy-4′-methoxychalcone (3b)

Yellow powder; mp 97-98^oC (lit.^[8] mp 107-108^oC); ¹H NMR data is in agreement with Lit^[8]. ¹³C NMR: d 56.2, 101.6, 108.3, 114.6, 120.9, 129.1, 129.6, 131.2, 131.8, 135.3, 145.0, 166.8, 167.3, 192.4. MS: m/z (%) 254 (M⁺, 100), 177, 165, 151, 122, 103, 77, 51.

2′-Hydroxy-6′-methoxychalcone (3c)

Yellow powder; mp 55^oC (lit.^[8] mp 65.0-65.5^oC); ¹H NMR data is in agreement with Lit^[8]. ¹³C NMR: d 55.5, 101.1, 110.5, 111.5, 127.1, 128.0, 128.5, 129.9, 134.9, 135.5, 142.5, 160.6, 164.4, 194.1. MS: m/z (%) 254 (M⁺, 75), 177, 150, 103, 91, 77, 51.

4-Chloro-2′-hydroxychalcone (3d)

Yellow powder, mp 144-146^oC (lit.^[13i] mp 153-156^oC); ¹H  and ¹³C NMR data is in agreement with Lit^[13i].  MS: m/z (%) 258 (M⁺, 100), 238, 165, 147, 120, 101, 78, 65, 51.

4-Chloro-2′-hydroxy-4′-methoxychalcone (3e)

Yellow powder; mp 115-116^oC; ¹H NMR: 3.9 (s, 3H), 6.5 (d, J = 8.8 Hz, 2H), 7.4-7.6 (m, 5H), 7.8 (d, J = 15.5 Hz, 1H), 7.9 (d, J = 15.5 Hz, 1H), 13.4 (s, 1H). ¹³C NMR: d 55.7, 101.2, 107.9, 114.1, 120.9, 129.4, 129.8, 131.3, 133.4, 136.7, 143.0, 166.4, 166.9, 191.6. MS

289 (M⁺+1, 43), 177, 151, 137, 122, 101, 75, 51

4-Chloro-2′-hydroxy-6′-methoxychalcone (3f)

Yellow powder; mp 114-116^oC; ¹H NMR: 3.9 (s, 3H), 6.4 (d, J = 8.0 Hz, 1H), 6.6 (d, J = 8.0 Hz, 1H), 7.4-7.6 (m, 5H), 7.8 (d, J = 15.4 Hz, 1H), 7.9 (d, J = 15.4 Hz, 1H), 13.1 (s, 1H). ¹³C NMR: d 56.1, 101.6, 111.1, 112.0, 128.1, 129.3, 129.7, 133.9, 136.2, 136.2, 141.5, 161.1, 165.0, 194.3. MS: m/z (%) 288 (M⁺, 100), 177, 150, 136, 122, 102, 75, 51.

2′-Hydroxy-3,4,5-trimethoxychalcone (3g)

Red needles; mp 146-148^oC (lit.^[7a] mp 180-182^oC); ¹H NMR data is  in agreement with Lit^[7a]. ¹³C NMR: d 56.3, 61.1, 106.0, 118.7, 118.9, 119.3, 129.7, 130.1, 136.5, 140.9, 145.7, 153.6, 163.7, 193.6. MS: m/z (%) 314 (M⁺, 98), 299, 283, 194, 181, 168, 147, 121, 93, 65.

2′-Hydroxy-3,4,5,5′-tetramethoxychalcone (3h)

Red needles; mp 115-117^oC; ¹H NMR: 3.7 (s, 3H), 3.8 (s, 3H), 3.9 (s, 6H), 7.0 (d, J = 8.8 Hz, 1H), 7.2 (m, 3H), 7.7 (d, J = 2.2 Hz, 1H), 7.8 (d, J = 15.4 Hz, 1H), 8.0 (d, J = 15.4 Hz, 1H), 12.1 (s, 1H). ¹³C NMR: d 56.4, 56.7, 60.7, 107.5, 114.9, 119.0, 121.3, 121.6, 123.6, 130.6, 140.7, 146.0, 152.2, 153.7, 156.5, 193.8. MS: m/z (%) 344 (M⁺, 100), 295, 194, 179, 151, 121, 107, 91, 65, 53.

2′-Hydroxy-3,4,5-trimethoxy-5′-methyl-chalcone (3i)

Red powder; mp 115^oC; ¹H NMR: 2.4 (s, 3H), 3.9 (s, 3H), 4.0 (s, 6H), 7.0 (m, 3H), 7.3 (d, J = 8.8 Hz, 1H), 7.5 (d, J = 15.4 Hz, 1H), 7.7 (s, 1H), 7.8 (d, J = 15.4 Hz, 1H), 12.7 (s, 1H). ¹³C NMR: d 20.7, 56.3, 56.4, 61.1, 103.3, 106.1, 118.5, 119.5, 119.7, 128.0, 129.3, 130.2, 137.6, 140.8, 145.6, 153.6, 161.7, 193.5. MS: m/z (%) 328 (M⁺, 100), 194, 181, 161, 135, 105, 77, 51.

5′-Chloro-2′-hydroxy-3,4,5-trimethoxychalcone (3j)

Yellow powder; mp 170-172^oC; ¹H NMR: 3.9 (s, 3H), 4.0 (s, 6H), 6.9 (s, 1H), 7.0 (d, J = 8.8 Hz, 2H), 7.4 (s, 1H), 7.5 (d, J = 15.4 Hz, 1H), 7.8 (s, 1H), 7.9 (d, J = 15.4 Hz, 1H), 12.8 (s, 1H). ¹³C NMR: d 56.4, 61.2, 106.2, 118.5, 120.4, 120.7, 123.5, 128.8, 129.8, 136.2, 141.2, 146.9, 153.6, 162.2, 192.7. MS: 348 (M⁺, 100), 194, 181, 155, 127, 83.

3′,5′-Dichloro-2′-hydroxy-3,4,5-trimethoxychalcone (3k)

Red powder; mp 144-146^oC; ¹H NMR: 3.9 (s, 3H), 4.0 (s, 6H), 6.9 (s, 1H), 7.3 (s, 1H), 7.4 (d, J = 15.4 Hz, 1H), 7.6 (d, J = 2.2 Hz, 1H), 7.8 (d, J = 2.2 Hz, 1H), 8.0 (d, J = 15.4 Hz, 1H), 13.5 (s, 1H). ¹³C NMR: d 56.4, 61.2, 106.4, 118.0, 121.2, 123.2, 124.3, 127.4, 129.6, 135.8, 147.9, 153.7, 192.4. MS: m/z (%) 384 (M⁺+1, 69), 351, 194, 179, 151, 133, 77, 63.

5′-Bromo-2′-hydroxy-3,4,5-trimethoxychalcone (3l)

Yellow powder; mp 165-167^oC; ¹H NMR: 3.9 (s, 3H), 4.0 (s, 6H), 6.9-7.6 (m, 5H), 7.9 (d, J = 15.4 Hz, 1H), 8.0 (d, J= 15.4 Hz, 1H), 12.8 (s, 1H). ¹³C NMR: d 56.5, 61.2, 106.3, 110.5, 118.5, 120.8, 121.4, 129.8, 131.8, 139.0, 141.3, 146.9, 153.7, 162.6, 192.6. MS: m/z (%) 394 (M⁺+1, 78), 194, 181, 168, 145, 119, 63.

2′-Hydroxy-3,4,5,4′-tetramethoxychalcone (3m)

Yellow powder; mp 118-119^oC; ¹H NMR: 3.8 (s, 3H), 3.9 (s, 3H), 4.0 (s, 6H), 6.5 (d, J = 2.2 Hz, 2H), 6.9 (s, 2H), 7.5 (d, J = 15.4 Hz, 1H), 7.8 (d, J = 15.4 Hz, 1H), 7.8 (s, 1H), 13.5 (s, 1H). ¹³C NMR: d 55.7, 56.3, 61.1, 101.1, 105.9, 107.9, 114.1, 119.6, 130.3, 131.3, 140.7, 144.6, 153.6, 166.3, 166.8, 191.7. MS: m/z (%) 344 (M⁺, 100), 194, 181, 151, 135, 77, 63.

2′-Hydroxy-3,4,5,6′-tetramethoxychalcone (3n)

Yellow powder; mp 123-124^oC; ¹H NMR: 3.8 (s, 3H), 3.9 (s, 6H), 4.0 (s, 3H), 6.5 (d, J = 8.08 Hz, 1H), 6.6 (d, J = 8.1 Hz, 1H), 6.9 (s, 2H), 7.4 (d, J= 15.5 Hz, 1H), 7.7 (s, 1H), 7.8 (d, J = 15.5 Hz, 1H,), 13.1 (s, 1H). ¹³C NMR: d 56.0, 56.3, 61.1, 101.7, 105.8, 111.1, 112.1, 127.1, 131.0, 136.0, 143.1, 153.5, 161.0, 164.9, 194.3. MS: m/z (%) 344 (M⁺, 100), 313, 194, 181, 151, 121, 91, 63.

2,4-Dichloro-2′-hydroxychalcone (3o)

Yellow powder; mp 150-152^oC (lit.^[7a] mp 178-180^oC); ¹H NMR data is  in agreement with Lit^[7a]. ¹³C NMR: d 118.8, 119.1, 119.9, 123.1, 127.7, 128.7, 129.8, 130.4, 131.6, 136.4, 136.8, 136.9, 140.0, 163.8, 193.3. MS: m/z (%) 294 (M⁺+1, 12), 257, 165, 136, 121, 99, 65.

2,4-Dichloro-2′-hydroxy-5′-methoxychalcone (3p)

Red powder; mp 140^oC; ¹H NMR: 3.8 (s, 3H), 7.0 (d, J = 8.8 Hz, 1H), 7.1-7.3 (m, 3H), 7.5 (d, J = 2.2 Hz, 1H), 7.6 (d, J = 15.4 Hz, 1H), 7.7 (d, J = 8.8 Hz, 1H), 8.2 (d, J = 15.4 Hz, 1H), 12.2 (s, 1H). ¹³C NMR: d 56.2, 113.0, 119.5, 119.6, 123.3, 124.3, 127.7, 128.7, 130.4, 131.6, 136.4, 136.9, 137.0, 140.1, 151.8, 158.1, 193.0. MS: m/z (%) 324 (M⁺+1, 75), 150, 135, 122, 99, 75.

2,4-Dichloro-2′-hydroxy-5′-methylchalcone (3q)

Red powder; mp 138-140^oC; ¹H NMR: 2.3 (s, 3H), 7.0 (d, J = 8.8 Hz, 1H), 7.2 (d, J = 15.4 Hz, 1H), 7.3 (m, 2H), 7.5 (d, J = 2.2 Hz, 1H), 7.6 (s, 1H), 7.7 (d, J = 8.04 Hz, 1H), 8.2 (d, J = 15.4 Hz, 1H), 12.5 (s, 1H). ¹³C NMR: d 20.7, 118.6, 119.6, 123.2, 127.7, 128.1, 128.7, 129.4, 130.3, 131.7, 136.4, 136.9, 137.9, 139.7, 161.7, 193.2. MS: m/z (%) 307 (M⁺, 11), 271, 161, 135, 106, 99, 77.

2,4,5′-Trichloro-2′-Hydroxy-chalcone (3r)

Yellow powder; mp 175-176^oC; ¹H NMR: 6.9 (d, J = 8.8 Hz, 1H), 7.3-7.4 (m, 3H), 7.5 (d, J = 15.4 Hz, 1H), 7.7 (d, J = 8.0 Hz, 1H), 7.8 (d, J = 3.0 Hz, 1H,), 8.3 (d, J = 15.4 Hz, 1H), 12.6 (s, 1H). ¹³C NMR: d 120.5, 122.3, 123.8, 127.7, 127.8, 128.8, 129.9, 130.4, 131.3, 136.6, 136.4, 137.4, 141.0, 162.2, 192.4. MS: m/z (%) 328 (M⁺+1, 20), 291, 181, 155, 136, 126, 99, 75.

2,4,3′,5′-Tetrachloro-2′-Hydroxy-chalcone (3s)

Yellow powder; mp 144-146^oC; ¹H NMR: 7.3-7.6 (m, 5H), 7.8 (d, J = 15.4 Hz, 1H), 8.3 (d, J = 15.4 Hz, 1H), 13.2 (s, 1H). ¹³C NMR: d 120.9, 121.8, 123.5, 127.5, 127.8, 128.9, 130.5, 131.0, 136.2, 136.8, 137.7, 142.0, 158.1, 192.2. MS: m/z (%) 362 (M⁺, 9), 327, 188, 160, 135, 109, 99, 75.

5′-Bromo-2,4-dichloro-2′-hydroxychalcone (3t)

Yellow powder; mp 170-172^oC; ¹H NMR: 6.9 (d, J = 8.8 Hz, 1H), 7.3-7.8 (m, 5H), 7.9 (d, J = 15.4 Hz, 1H), 8.3 (d, J= 15.4 Hz, 1H), 12.6 (s, 1H). ¹³C NMR: d 110.6, 120.9, 122.3, 127.8, 128.8, 130.4, 131.9, 136.6, 137.4, 139.4, 141.0, 162.7, 192.3. MS: m/z (%) 372 (M⁺, 80), 99, 75.

2,4-Dichloro-2′-Hydroxy-4′-methoxychalcone (3u)

Yellow powder; mp 185-187^oC; ¹H NMR: 3.9 (s, 3H), 7.0 (m, 2H), 7.3-7.4 (m, 2H), 7.5 (d, J = 15.4 Hz, 1H), 7.7 (d, J = 8.8 Hz, 1H), 7.8 (d, J = 8.8 Hz, 1H), 8.2 (d, J = 15.4 Hz, 1H), 13.3 (s, 1H). ¹³C NMR: d 55.8, 101.2, 108.1, 114.0, 123.4, 127.7, 128.6, 130.3, 131.3, 131.8, 136.2, 136.7, 138.9, 166.6, 166.9, 191.3. MS: m/z (%) 323 (M⁺, 100), 150.10, 99, 75.

2,4-Dichloro-2′-hydroxy-6′-methoxychalcone (3v)

Red powder; mp 163-166^oC; ¹H NMR: 3.9 (s, 3H), 6.4 (d, J = 8.1 Hz, 1H), 6.6 (d, J = 8.1 Hz, 1H), 7.3-7.4 (m, 3H), 7.6 (d, J = 8.0 Hz, 1H), 7.8 (d, J = 15.4 Hz, 1H), 8.1 (d, J = 15.4 Hz, 1H), 13.0 (s, 1H). ¹³C NMR: d 56.1, 101.6, 111.1, 111.9, 127.6, 128.6, 130.2, 130.4, 132.3, 136.1, 136.2, 136.4, 137.2, 161.0, 165.1, 194.0. MS: m/z (%) 323 (M⁺, 100), 150, 99, 75.

6-Chloroflavanone (4a)

Pale yellow powder; mp 82-83^oC; ¹H and ¹³C NMR data is in agreement with Lit^[17]. MS: m/z (%) 258 (M⁺, 86), 154, 126, 104, 77, 63.

6-Methoxyflavanone (4b)

Yellow powder; mp 133-135^oC (lit.^[14c] mp 142-143^oC); ¹H and ¹³C NMR data is in agreement with Lit^[14c].  MS: m/z (%) 254 (M⁺, 71), 177, 150, 135, 122, 104, 77, 51.

6-Methylflavanone (4c)

Yellowish white powder; mp 99-100^oC; ¹H NMR: 2.3 (s, 3H), 2.9 (dd, J = 16.8, 2.9 Hz, 1H), 3.1 (dd, J = 16.8, 13.2 Hz, 1H), 5.5 (dd, J = 13.2, 2.9 Hz, 1H,), 6.9-7.7 (m, 8H). ¹³C NMR: d 20.5, 44.8, 79.7, 118.0, 126.2, 126.7, 128.4, 128.8, 131.4, 137.4, 139.0, 159.7, 192.3. MS: m/z (%) 238 (M⁺, 64), 161, 134, 105, 77, 51.

6,8-Dichloroflavanone (4d)

Yellow powder; mp 104-106^oC; ¹H NMR: 3.0 (dd, J = 17.0, 3.6 Hz, 1H), 3.1 (dd, J = 17.0, 13.0 Hz, 1H), 5.6 (dd, J = 13.0, 3.6 Hz, 1H), 7.5-7.8 (m, 7H). ¹³C NMR: d 43.9, 80.1, 122.6, 124.4, 125.2, 126.9, 129.9, 129.1, 135.8, 137.8, 155.8, 190.1. MS: m/z (%) 294 (M⁺+1, 43), 190, 188, 160, 132, 104, 77, 51.

6-Bromoflavanone (4e)

Yellow powder; mp 103-105^oC; ¹H and ¹³C NMR data is in agreement with Lit^[17]. MS: m/z (%) 303 (M⁺, 77), 254, 227, 198, 170, 150, 104, 77, 63.

6,4′-Dichloroflavanone (4f)

Yellowish white powder; mp 148-150^oC; ¹H NMR: 2.9 (dd, J = 17.0, 2.9 Hz, 1H,), 3.0 (dd, J = 17.0, 13.3 Hz, 1H), 5.5 (dd, J = 13.3, 2.9 Hz, 1H), 7.0-7.9 (m, 7H). ¹³C NMR: d 43.7, 77.4, 119.9, 121.8, 126.5, 127.5, 127.6, 129.3, 135.0, 135.9, 136.3, 155.5, 189.7. MS: m/z (%) 293 (M⁺, 17), 154, 126, 98, 75, 63.

4′-Chloro-6-Methyl-flavanone (4g)

White powder; mp 118-120^oC; ¹H NMR: 2.3 (s, 3H), 2.9 (dd, J = 17.0, 3.0 Hz, 1H), 3.0 (dd, J = 17.0, 13.2 Hz, 1H), 5.4 (dd, J = 13.2, 3.0 Hz, 1H,), 6.9-7.4 (m, 7H). ¹³C NMR: d 20.5, 44.7, 77.4, 117.9, 120.6, 126.7, 129.1, 131.4, 134.6, 137.5, 159.5, 191.9. MS: m/z (%) 272 (M⁺, 54), 161, 134, 105, 77, 51.

6,8,4′-Trichloroflavanone (4h)

White powder; mp 131-133^oC; ¹H NMR: 2.9 (dd, J = 17.0, 3.0 Hz, 1H), 3.1 (dd, , J = 17.0, 12.0 Hz, 1H), 5.6 (dd, J = 12.0, 3.0 Hz, 1H), 7.3-7.8 (m, 6H). ¹³C NMR: d 43.8, 77.5, 122.6, 124.4, 125.2, 127.2, 129.3, 135.0, 135.9, 136.3, 155.5, 189.7. MS: m/z (%) 328 (M⁺+1, 33), 188, 138, 77, 51.

4′-Chloro-6-methoxyflavanone (4i)

Pale yellow powder; mp 104^oC (lit.^[14c] mp 114-115^oC); ¹H and ¹³C NMR data is in agreement with Lit^[14c]. MS: m/z (%) 288 (M⁺, 32), 150, 135, 122, 103, 77, 51.

6-Bromo-4′-chloroflavanone (4j)

Yellowish powder; mp 157-159^oC; ¹H NMR: 2.9 (dd, J = 16.8, 2.9 Hz, 1H), 3.0 (dd, J = 16.8, 13.2 Hz, 1H), 5.4 (dd, J = 13.2, 2.9 Hz, 1H), 6.9-8.0 (m, 7H). ¹³C NMR: d 44.2, 77.4, 114.6, 120.3, 122.2, 127.6, 129.2, 129.6, 134.9, 136.8, 138.9, 160.2, 190.3. MS: m/z (%) 338 (M⁺+1, 40), 198, 170, 138, 103, 77, 63.

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