* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With sodium hydroxide In ethanol; water at 0 - 20℃;
General procedure: To a solution of substituted benzaldehydes (6a1–d1, 6e, 6f) and acetone (10–25 equivalents, excess) in ethanol was added 20percent (w/v) aqueous NaOH at 0–5°C. The reaction mixture was stirred at ambient temperature and the progress of the reaction was monitored by TLC. When the substituted benzaldehyde was consumed, the excess acetone was removed in vacuo; cold water was then added and the resulting solution was acidified with 3M HCl. The product which appeared as a solid was collected by vacuum filtration, washed with water and dried in vacuo. The residue was purified by column chromatography or recrystallized from appropriate solvent system to yield the substituted 4-phenylbut-3-en-2-ones 7a1–d1, 7e and 7f.
87%
With sodium hydroxide In ethanol; water at 20℃; for 15 h;
4-(4-Hydroxy-3-methoxy-phenyl)but-3-ene-2-one: To a solution of acetone (15.30 g, 263.76 mmol) in a mixture of ethanol (35 niL) and water (15 mL) were added sodium hydroxide (2.90 g,72.54 mmol) and 4-hydroxy-3-methoxybenzaldehyde (5.01 g, 32.97 mmol). The reaction mixture was stirred at room temperature for 15 h. The reaction was cooled to 0° C and quenched with 2.0 N hydrochloric acid until the solution became slightly acidic. The solution was extracted with ethyl acetate (4x 100 mL). The combined organic layers were washed with water (50 mL) and saturated aqueous sodium chloride (50 mL). EPO <DP n="65"/>The organic layer was dried over magnesium sulfate, filtered, and concentrated at reduced pressure to afford 4-(4-hydroxy-3-methoxy-phenyl)but-3-ene-2-one (5.52 g, 87percent yield) as a yellow solid: MS (EI) for CH12O3: 193 (MH+).
87%
at 20℃; for 1 h; Green chemistry
General procedure: A mixture of aromatic aldehyde (2 mmol) and ketone (2 mmol) was added in one portion to 11 mol percent of dry catalyst A-2XMP at RT and was stirred for 1 h. Progress of the reaction was monitored by TLC (hexane:ethylacetate :: 88:12,v/v). After completion of the reaction, excess of ethyl alcohol was added. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. Crystallization was observed at RT. Pure products (15a-18a) were purified by recrystallization from ethyl alcohol giving 87-94percent yields.
85%
at 20℃; for 3 h;
4.1.2. General procedure for the preparation of compounds (1f,g). Toa stirred solution of p-hydroxybenzaldehydes (10 mmol) in anhydrousacetone (15 mL) was added 10percent NaOH solution (25 mL), andthe mixture was stirred for 3 h at room temperature. Acidification using 10percent HCl until the color change of Congo red paper from red toblue. The resulting mixture was extracted with dichloromethane(30 mL3). The organic layers werewashed with brine (20 mL) and dried over MgSO4 were filtered, evaporated, and the residue waspurified by column chromatography (ethyl acetate/n-hexane1:10)to give pure 1f-g.
72%
at 20℃; for 2 h;
Vanillin (20 g) was dissolved in acetone (50 mL) in a round bottomflask and 40percent KOH (5 mL) was added to this reaction mixture.It was kept on stirring at room temperature. After the completionof reaction (monitored by TLC), reaction mixture was acidified withdilute hydrochloric acid until pH 7 was achieved. It was thenpoured in ice-cold water, filtered and dried to get the desired product,that is, vinyldenacetone (VDA). The physical data of vinyldenacetoneis given below:4.2.1. (E)-4-(4-Hydroxy-3-methoxyphenyl)but-en-2-one (VDA)Yield 72percent; mp 71–73 C. 1H NMR (CDCl3, 500 MHz, d, TMS = 0):2.36 (s, 3H), 3.91 (s, 3H), 6.58 (d, J = 16.5 Hz, 1H), 6.92 (d, J = 7.5 Hz,1H), 7.04–7.08 (m, 2H), 7.45 (d, J = 16.5 Hz, 1H). 13C NMR (CDCl3,125 MHz, d, TMS = 0): 27.22, 55.84, 109.56, 114.99, 123.52,124.82, 126.79, 144.03, 147.08, 148.51, 198.72.
72%
With potassium hydroxide In water at 20℃; for 2 h;
Vanillin (20g) was dissolved in acetone (50ml) in a round bottom flask and 40percent KOH (5ml) was added to this reaction mixture. It was kept on stirring at room temperature. After the completion of reaction (monitored by TLC), reaction mixture was acidified with dilute hydrochloric acid until pH 7 was achieved. It was then poured in ice-cold water, filtered and dried to get the desired product i.e. vinyldenacetone (VDA). The physical data of vinyldenacetone is given below. Yield 72percent; mp 71–73°C. 1H NMR (CDCl3, 500MHz, δ, TMS=0): 2.36 (s, 3H), 3.91 (s, 3H), 6.58 (d, J=16.5Hz, 1H), 6.92 (d, J=7.5Hz, 1H), 7.04–7.08 (m, 2H), 7.45 (d, J=16.5Hz, 1H). 13C NMR (CDCl3, 125MHz, δ, TMS=0): 27.22, 55.84, 109.56, 114.99, 123.52, 124.82, 126.79, 144.03, 147.08, 148.51, 198.72
Reference：
[1] Synthesis, 2008, # 22, p. 3675 - 3681
[2] Tetrahedron, 2009, vol. 65, # 31, p. 6047 - 6049
[3] Amino Acids, 2013, vol. 45, # 2, p. 327 - 338
[4] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 13, p. 2839 - 2844
[5] Patent: WO2006/33943, 2006, A2, . Location in patent: Page/Page column 63-64
[6] Advanced Synthesis and Catalysis, 2011, vol. 353, # 6, p. 871 - 878
[7] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2013, vol. 52, # 8, p. 1137 - 1145
[8] Tetrahedron, 2013, vol. 69, # 2, p. 653 - 657
[9] Pest Management Science, 2001, vol. 57, # 3, p. 289 - 300
[10] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1981, p. 82 - 87
[11] Synthetic Communications, 2005, vol. 35, # 2, p. 213 - 222
[12] ACS Chemical Neuroscience, 2019,
[13] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 22, p. 7165 - 7180
[14] European Journal of Medicinal Chemistry, 2016, vol. 116, p. 102 - 115
[15] Journal of Medicinal Chemistry, 2017, vol. 60, # 23, p. 9821 - 9837
[16] European Journal of Medicinal Chemistry, 1988, vol. 23, # 4, p. 379 - 380
[17] ACS Medicinal Chemistry Letters, 2016, vol. 7, # 7, p. 686 - 691
[18] Journal of Natural Products, 2012, vol. 75, # 12, p. 2088 - 2093
[19] Green Chemistry, 2012, vol. 14, # 9, p. 2375 - 2379
[20] Bioorganic and Medicinal Chemistry Letters, 1997, vol. 7, # 24, p. 3091 - 3094
[21] Phytochemistry (Elsevier), 1977, vol. 16, p. 1587 - 1590
[22] Phytochemistry, 1998, vol. 48, # 5, p. 889 - 891
[23] Tetrahedron Letters, 2002, vol. 43, # 19, p. 3597 - 3599
[24] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 11, p. 3811 - 3820
[25] Biochemical Pharmacology, 2006, vol. 72, # 8, p. 928 - 940
[26] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 18, p. 6193 - 6199
[27] Patent: US2006/258752, 2006, A1, . Location in patent: Page/Page column 4; sheet 2
[28] Tetrahedron Letters, 2012, vol. 53, # 32, p. 4173 - 4178
[29] Food Chemistry, 2014, vol. 165, p. 191 - 197
[30] Molecules, 2017, vol. 22, # 1,
[31] Journal of Agricultural and Food Chemistry, 2018, vol. 66, # 30, p. 7983 - 7994
[32] Medicinal Chemistry Research, 2019,
2
[ 121-33-5 ]
[ 1439-36-7 ]
[ 1080-12-2 ]
Yield
Reaction Conditions
Operation in experiment
98%
at 90℃; for 0.5 h; Green chemistry
General procedure: A suspension of an appropriate aromatic aldehyde (1 eq.), and ylide I or II (1.3–1.5 eq.) inwater (4–10 mL) was stirred at 90 °C for 0.5–24 h. Next, the heterogeneous reaction mixturewas cooled to room temperature, and the aqueous phase was extracted with DCM (3 10 mL).The solvent was evaporated under diminished pressure. Column chromatography (hexane–ethylacetate, or chloroform–methanol) of the residue gave the E-alkene as the major product.
Reference：
[1] Molecules, 2018, vol. 23, # 9,
[2] Phosphorus, Sulfur and Silicon and Related Elements, 1998, vol. 143, p. 33 - 44
[3] Liebigs Annalen der Chemie, 1983, # 12, p. 2135 - 2140
3
[ 29121-62-8 ]
[ 1080-12-2 ]
Reference：
[1] Patent: US3934032, 1976, A,
4
[ 52328-99-1 ]
[ 1080-12-2 ]
Reference：
[1] Journal of Natural Products, 2014, vol. 77, # 10, p. 2206 - 2217
5
[ 121-33-5 ]
[ 1080-12-2 ]
Reference：
[1] Journal of the Chemical Society, 1938, p. 1568,1570
[2] Zhurnal Obshchei Khimii, 1948, vol. 18, p. 1386,1390[3] Chem.Abstr., 1949, p. 2185
[4] Journal of the American Pharmaceutical Association (1912-1977), 1946, vol. 35, p. 188,189
[5] Journal of Natural Products, 2014, vol. 77, # 10, p. 2206 - 2217
6
[ 121-33-5 ]
[ 75-05-8 ]
[ 1080-12-2 ]
Reference：
[1] Green Chemistry, 2012, vol. 14, # 9, p. 2375 - 2379
With nickel boride; hydrogen; In methanol; at 25℃; for 1.5h;
General procedure: Sodium tetrahydridoborate, 0.46 g (12.1 mmol), was added in portions with stirring to a solution of 1.10 g (4.63 mmol) of NiCl2·6H2O in 20 mL of methanol, cooled to 0 C. The resulting suspension was stirred for 15 min at 0 C and refluxed for 20 min under argon. The mixture was then cooled to room temperature, 9.25 mmol of ketone 1a-1g was added, and the miixture was stirred in a hydrogen atmosphere. When the green color of the reaction mixture disappeared, hydrogen supply was turned off, and the mixture was filtered. The precipitate of nickel boride was additionally washed with a small amount of methanol, and the filtrate was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (20 mL), the solution was washed with a saturated aqueous solution of ammonium chloride (20 mL), the organic phase was separated, and the aqueous phase was extracted with ethyl acetate (10 mL). The combined organic phases were washed with saturated solutions of NaHCO3 and NaCl (10 mL each), dried over Na2SO4, and evaporated under reduced pressure. The residue was purified by crystallization from appropriate solvent mixture or by column chromatography.
With sodium hydroxide; In ethanol; water; at 0 - 20℃;
General procedure: To a solution of substituted benzaldehydes (6a1-d1, 6e, 6f) and acetone (10-25 equivalents, excess) in ethanol was added 20% (w/v) aqueous NaOH at 0-5C. The reaction mixture was stirred at ambient temperature and the progress of the reaction was monitored by TLC. When the substituted benzaldehyde was consumed, the excess acetone was removed in vacuo; cold water was then added and the resulting solution was acidified with 3M HCl. The product which appeared as a solid was collected by vacuum filtration, washed with water and dried in vacuo. The residue was purified by column chromatography or recrystallized from appropriate solvent system to yield the substituted 4-phenylbut-3-en-2-ones 7a1-d1, 7e and 7f.
87%
With sodium hydroxide; In ethanol; water; at 20℃; for 15h;
4-(4-Hydroxy-3-methoxy-phenyl)but-3-ene-2-one: To a solution of acetone (15.30 g, 263.76 mmol) in a mixture of ethanol (35 niL) and water (15 mL) were added sodium hydroxide (2.90 g,72.54 mmol) and 4-hydroxy-3-methoxybenzaldehyde (5.01 g, 32.97 mmol). The reaction mixture was stirred at room temperature for 15 h. The reaction was cooled to 0 C and quenched with 2.0 N hydrochloric acid until the solution became slightly acidic. The solution was extracted with ethyl acetate (4x 100 mL). The combined organic layers were washed with water (50 mL) and saturated aqueous sodium chloride (50 mL). EPO <DP n="65"/>The organic layer was dried over magnesium sulfate, filtered, and concentrated at reduced pressure to afford 4-(4-hydroxy-3-methoxy-phenyl)but-3-ene-2-one (5.52 g, 87% yield) as a yellow solid: MS (EI) for CH12O3: 193 (MH+).
87%
With macroporous anion exchange resin (A-2XMP); at 20℃; for 1h;Green chemistry;
General procedure: A mixture of aromatic aldehyde (2 mmol) and ketone (2 mmol) was added in one portion to 11 mol % of dry catalyst A-2XMP at RT and was stirred for 1 h. Progress of the reaction was monitored by TLC (hexane:ethylacetate :: 88:12,v/v). After completion of the reaction, excess of ethyl alcohol was added. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. Crystallization was observed at RT. Pure products (15a-18a) were purified by recrystallization from ethyl alcohol giving 87-94% yields.
85%
With sodium hydroxide; at 20℃; for 3h;
4.1.2. General procedure for the preparation of compounds (1f,g). Toa stirred solution of p-hydroxybenzaldehydes (10 mmol) in anhydrousacetone (15 mL) was added 10% NaOH solution (25 mL), andthe mixture was stirred for 3 h at room temperature. Acidification using 10% HCl until the color change of Congo red paper from red toblue. The resulting mixture was extracted with dichloromethane(30 mL3). The organic layers werewashed with brine (20 mL) and dried over MgSO4 were filtered, evaporated, and the residue waspurified by column chromatography (ethyl acetate/n-hexane1:10)to give pure 1f-g.
80%
With sodium hydroxide; In methanol; at 20℃;
General procedure: For the preparation of analog 4, vanillin (5.6 mmol) wasused in a similar procedure as for compounds 2, followed bythe addition of an excess of acetone (3.0 cm3) to inhibit theformation of compound 2a and to furnish the expected intermediate4 for further use. Compound 4 (1.5 mmol) was firstdissolved in methanol, followed by the addition of indole-3-carboxaldehyde (1.7 mmol) to the solution. Sequentially,saturated NaOH in methanol was added dropwise, and themixture was stirred at room temperature. After 1 day, thereaction was neutralized and concentrated under reduced pressure, followed by extraction with EtOAc. The combinedorganic layers were washed with 30 cm3 brine and dried overanhydrous MgSO4,filtered, and concentrated under reducedpressure. Finally, the crude mixture was further purified byreversed-phase (C18) column chromatography in order toobtain indole derivative 5.
72%
With potassium hydroxide; at 20℃; for 2h;
Vanillin (20 g) was dissolved in acetone (50 mL) in a round bottomflask and 40% KOH (5 mL) was added to this reaction mixture.It was kept on stirring at room temperature. After the completionof reaction (monitored by TLC), reaction mixture was acidified withdilute hydrochloric acid until pH 7 was achieved. It was thenpoured in ice-cold water, filtered and dried to get the desired product,that is, vinyldenacetone (VDA). The physical data of vinyldenacetoneis given below:4.2.1. (E)-4-(4-Hydroxy-3-methoxyphenyl)but-en-2-one (VDA)Yield 72%; mp 71-73 C. 1H NMR (CDCl3, 500 MHz, d, TMS = 0):2.36 (s, 3H), 3.91 (s, 3H), 6.58 (d, J = 16.5 Hz, 1H), 6.92 (d, J = 7.5 Hz,1H), 7.04-7.08 (m, 2H), 7.45 (d, J = 16.5 Hz, 1H). 13C NMR (CDCl3,125 MHz, d, TMS = 0): 27.22, 55.84, 109.56, 114.99, 123.52,124.82, 126.79, 144.03, 147.08, 148.51, 198.72.
72%
With potassium hydroxide; In water; at 20℃; for 2h;
Vanillin (20g) was dissolved in acetone (50ml) in a round bottom flask and 40% KOH (5ml) was added to this reaction mixture. It was kept on stirring at room temperature. After the completion of reaction (monitored by TLC), reaction mixture was acidified with dilute hydrochloric acid until pH 7 was achieved. It was then poured in ice-cold water, filtered and dried to get the desired product i.e. vinyldenacetone (VDA). The physical data of vinyldenacetone is given below. Yield 72%; mp 71-73C. 1H NMR (CDCl3, 500MHz, delta, TMS=0): 2.36 (s, 3H), 3.91 (s, 3H), 6.58 (d, J=16.5Hz, 1H), 6.92 (d, J=7.5Hz, 1H), 7.04-7.08 (m, 2H), 7.45 (d, J=16.5Hz, 1H). 13C NMR (CDCl3, 125MHz, delta, TMS=0): 27.22, 55.84, 109.56, 114.99, 123.52, 124.82, 126.79, 144.03, 147.08, 148.51, 198.72
With sodium hydroxide; In water; ethyl acetate;
A second series of compounds 6a-6c, 6f, 6g, 6j-6q were synthesized containing two aryl rings separated by a five carbon unsaturated spacer having a single carbonyl. These compounds were designed to test the importance the length of the spacer and the number of carbonyls in the spacer. The synthesis of compounds 6a-6c, 6f, 6g, 6j-6q involves a base catalyzed aldol reaction with acetone and substituted benzaldehydes as depicted in FIG. 3. Two additional compounds, 6r and 6s, having a five carbon spacer contain two different aryl rings. These compounds were designed to test the importance of symmetry in compounds with a five carbon spacer. As depicted in FIG. 3, these compounds were synthesized using consecutive base catalyzed aldol reactions as described by Masuda (Masuda, T., Jitoe, A., Isobe. J., Nakatani, N., Yonemori, S. 1993. Anti-Oxidative and Anti-inflammatory Curcumin-Related Phenolics from Rhizomes of Curcuma Domestica. 32:1557-1560). Two additional compounds 7a and 7f contain a single aryl ring and a 4-carbon unsaturated chain with a carbonyl These compounds were designed to test the importance of the necessity of two aryl rings. Compounds 7a and 7f were synthesized as depicted in FIG. 3 using a base catalyzed aldol reaction with excess acetone and substituted benzaldehydes. Two compounds, 8b and 9b, were synthesized as shown in FIG. 3. These compounds contain a saturated five carbon spacer. Compound 9b has a hydroxyl group on the spacer rather than a carbonyl. These compounds were designed to test the importance of unsaturation and the necessity of a carbonyl in the spacer. The synthesis of these compounds was performed by reacting compound 6b with palladium on activated charcoal under a hydrogen atmosphere to give a mixture of compounds 8b and 9b, which were separated by chromatography. Compounds 9a-9v contain two identical aryl rings separated by an unsaturated five carbon spacer having a single carbonyl whereas compounds 9x and 9y have two different aryl rings. These compounds were designed to test the importance of the length of the spacer between the two aryl rings. Compounds 9a-9w were prepared from acetone and a substituted benzaldehyde in a base catalyzed aldol reaction as described by Masuda. In the case of phenolic benzaldehydes, the phenol was protected with a methoxymethyl group prior to the aldol reaction and deprotected later to give the free phenol. Compounds 9u and 9v were prepared from 9a and 9r respectively by reaction with acetic anhydride as described by Ali. Compounds 9x and 9y were prepared using two consecutive base catalyzed aldol reactions.
With sodium hydroxide; In water; at 20℃;
25 ml 20% aq. sodium hydroxide was added to the acetone (30 ml) solution of vanillin (5.0 g, 32.89 mmol) and then this was stirred overnight at room temperature. The reaction mixture was diluted with ice water and 35 ml conc. HCl was added, a brown precipitate formed which was filtered, washed with cold water and dried to obtain (E)-4-(4'-hydroxy-3'-methoxyphenyl)-3-buten-2-one.
General procedure: A suspension of an appropriate aromatic aldehyde (1 eq.), and ylide I or II (1.3-1.5 eq.) inwater (4-10 mL) was stirred at 90 C for 0.5-24 h. Next, the heterogeneous reaction mixturewas cooled to room temperature, and the aqueous phase was extracted with DCM (3 10 mL).The solvent was evaporated under diminished pressure. Column chromatography (hexane-ethylacetate, or chloroform-methanol) of the residue gave the E-alkene as the major product.
(a) Vanillin (9.12 g, 0.06 mole) was dissolved in 36 mL of acetone and 12.5 mL of 50% aq. NaOH solution was added dropwise with vigorous stirring. To the resulting solid was added 25 mL of water and the dark red solution was refluxed for 5 min. This reaction mixture was kept at room temperature for 24 h and acidified with acetic acid. The reaction mixture was concentrated to provide a yellow solid, which was filtered, washed with water and dried to yield 10.2 g (88%) of (E)-1-(3-methoxy-4-hydroxyphenyl)-1-butene-3-one, I-1a: 1H NMR (300 MHz, CDCl3) delta7.43 (d, 1H, J=16.3 Hz), 7.04-7.09 (m, 2H), 6.91 (d, 1H, J=7.9 Hz), 6.57 (d, 1H, J=16.3 Hz), 6.02 (s, 1H), 3.92 (s, 3H), 2.35 (s, 3H).
43
[ 1080-12-2 ]
[ 95-92-1 ]
ethyl (E)-6-(4-hydroxy-3-methoxyphenyl)-2,4-dioxo-5-hexenoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
8.4 g (55%)
With hydrogenchloride; In ethanol;
(b) Sodium metal (3.7 g, 0.16 mole) was dissolved in 100 mL of absolute ethanol under an inert atmosphere. An solution of 16.2g (953 mmol) of E-1-(3-methoxy-4-hydroxyphenyl)-1-butene-3-one, I-1a, of ethanol was then added slowly over 30 min to the sodium ethoxide solution. After the addition the reaction mixture was stirred at for 15 min followed by the addition of diethyl oxalate (7.7 g, 0.53 mole) and the dark red solution was stirred at room temperature for 5 h. Concentrated HCl was added to the reaction mixture until acidic. A dark yellow solid separated out which was stirred in an ice bath for 1 h. The solid was filtered, washed and dried to afford 8.4 g (55%) of the desired ethyl (E)-6-(4-hydroxy-3-methoxyphenyl)-2,4-dioxo-5-hexenoate, I-1b: 1H NMR (300 MHz, CDCl3) 6 14.86 (br s, 1H), 7.54 (d, 1H, J=15.9 Hz), 7.00 (d, 1H, J=8.3 Hz), 6.93 (s, 1H), 6.81 (d, 1H, J=8.3 Hz), 6.36-6.41 (m, 2H), 5.84 (s, 1H), 4.23 (q, 2H, J=7.2 Hz), 3.81 (s, 3H), 1.25 (t, 3H, J=7.2 Hz).
8.4 g (55%)
With hydrogenchloride; In ethanol;
(b) Sodium metal (3.7 g, 0.16 mole) was dissolved in 100 mL of absolute ethanol under an inert atmosphere. An solution of 16.2 g (953 mmol) of E-1-(3-methoxy-4-hydroxyphenyl)-1-butene-3-one, I-1a, of ethanol was then added slowly over 30 min to the sodium ethoxide solution. After the addition the reaction mixture was stirred at for 15 min followed by the addition of diethyl oxalate (7.7 g, 0.53 mole) and the dark red solution was stirred at room temperature for 5 h. Concentrated HCl was added to the reaction mixture until acidic. A dark yellow solid separated out which was stirred in an ice bath for 1 h. The solid was filtered, washed and dried to afford 8.4 g (55%) of the desired ethyl (E)-6-(4-hydroxy-3-methoxyphenyl)-2,4-dioxo-5-hexenoate, I-1b: 1H NMR (300 MHz, CDCl3) delta14.86 (br s, 1H), 7.54 (d, 1H, J=15.9 Hz), 7.00 (d, 1H, J=8.3 Hz), 6.93 (s, 1H), 6.81 (d, 1H, J=8.3 Hz), 6.36-6.41 (m, 2H), 5.84 (s, 1H), 4.23 (q, 2H, J=7.2 Hz), 3.81 (s, 3H), 1.25 (t, 3H, J=7.2 Hz).
With hydrogenchloride; sodium hydroxide; In ethanol;
EXAMPLE 2 4-[4'1-(2,3-Epoxypropoxy)-3'-methoxyphenyl]-3-buten-2-one (DZE,3) 20 g Dehydrozingerone and 4 g NaOH were dissolved under stirring in absoluted ethanol overnight. Then 5 ml chlorohydrin was added and then heated. After cooling, the inorganic salt was filtered off, the filtrate was diluted with methanol, and then treated with conc. HCl to pH 7.0. The separated solid was recystallized from ethanol to afford 4-[4'-(2,3-epoxypropoxy)-3'-methoxyphenyl]-3 buten-2-one (DZE, 3) 75% as colorless needles. mp: 123-124 C. UV lambdamax nm (log epsilon): 239.5(4.16), 331(4.41). 1 H-NMR(CDCl3): delta7.42-7.50 (d,1H, CH=CH), 6.92-14(m,3H, Ar 6.57-6.65 (d,1H, Ar--CH), 4.02-4.37(m,2H, CH2 OAr), 3.92(s,3H, OCH3), 3.40-3.42(br s,1H, CHO), 2.75-2.95(m,2H, CH2 of the epoxide), 2.38(s,3H, CH3). IR (KBr): 1650 cm-1 (carbonyl, C=0). FAB-MS m/z: 249[M+H]+.
vanillin (4-hydroxy-3-methoxybenzaldehyde)[ No CAS ]
[ 29121-62-8 ]
[ 1080-12-2 ]
Yield
Reaction Conditions
Operation in experiment
With sodium hydroxide; In water; acetone;
The 1-[2-methoxy-4-(3-oxobut-1-enyl)phenoxy]-2,3,-epoxypropane used as starting material may be obtained as follows: A mixture of 12.5 g. of vanillin (4-hydroxy-3-methoxybenzaldehyde), 50 ml. of acetone and 40 ml. of 9% aqueous sodium hydroxide solution is kept at room temperature for 30 days. 100 Ml. of water are added, the excess of acetone is removed by evaporation under reduced pressure and the residue is acidified with 20% aqueous acetic acid solution. The mixture is filtered and the solid product is crystallized from aqueous ethanol. There is thus obtained 4-(4-hydroxy-3-methoxyphenyl)but-3-en-2-one, m.p. 119-122C.
piperidine-4-carboxylic acid ethyl ester hydrochloride[ No CAS ]
5-[(4-ethoxycarbonyl)piperidyl]-1-(3-methoxy-4-hydroxyphenyl)-1-penten-3-one hydrochloride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
42%
Example 8 5-[(4-Ethoxycarbonyl)piperidyl]-1-(3-methoxy-4-hydroxyphenyl)-1-penten-3-one hydrochloride Compound No.8 0.485g (2.5mmol) of 4-ethoxycarbonylpiperidine hydrochloride and 0.6g (20mmol) of paraformaldehyde were dissolved in anhydrous ethanol (5ml). The pH value of the solution was adjusted to pH =2-3 with concentrated hydrochloric acid and the reaction mixture was refluxed and stirred for 2hr. After the solid was dissolved, 0.48g (2.5mmol) of 4-(3-methoxy-4-hydroxyphenyl)-3-buten-2-one (prepared as described in preparation 10) was added to the above reaction mixture. The solution was further refluxed and stirred for 12hr. TLC showed the reaction was completed, after staying overnight at room temperature, the precipitated solid was collected by filtration and then recrystallized from 95% ethanol and dried to give 0.42g of crystals, yield: 42%, mp: 194-197C. 1H-NMR deltappm (DMSO-d6): 1.20(t, 3H, J=7.2 Hz, COOCH2CH3), 1.9-2.2 (brs, 5H, (CH2)2CH), 3.20-3.58(m, 6H, 3NCH2), 3.80(s, 3H, OCH3), 4.06-4.12(q, 2H, J=7.2 Hz, COOCH2CH3), 6.76(d, J=16.0Hz, 1H, =CHCO), 6.82(d, J=8.5Hz 1H, ArH), 7.16(d, J=8.5Hz, 1H, ArH), 7.31(d, J=1.5Hz, 1H, ArH), 7.60(d, J=16.0Hz, 1H, CH=). MS (m/z): 361(M+, 20), 316(M+-45, 10), 288(M+-73, 5), 204(M+-157, 100).
4-(E)-[(2RS,3RS)-2,3-dihydro-2-(4-hydroxy-3-methoxy-phenyl)-7-methoxy-3-acetyl-1-benzofuran-5yl]but-3-en-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
89%
With ammonium cerium (IV) nitrate; In tetrahydrofuran; at 0℃; for 1.5h;Inert atmosphere;
General procedure: 4.1.3. General procedure for the preparation of natural occurring()-dihydrobenzofurans (2a,b). A solution of 1a,b (2 mmol) in THF(50 mL) was added dropwise with ceric ammonium nitrate (1.64 g,3 mmol)/THF (50 mL) under the protection of dried nitrogen at 0 Cfor 1.5 h. Then, quenched with brine (20 mL), and concentrated invacuo to remove THF, and extracted with CH2Cl2 (40 mL3). Theorganic layer was combined, dried over MgSO4, and filtered in sequence.The filtrate was concentrated in vacuo to remove solvent.The resulting residue was purified by silica gel column chromatography(ethyl acetate/n-hexane1:6) to give 2a,b, respectively.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
