Structure of 34956-31-5
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CAS No. : | 34956-31-5 |
Formula : | C11H13NO2 |
M.W : | 191.23 |
SMILES Code : | CC(NC1=CC=C(C(C)=O)C(C)=C1)=O |
MDL No. : | MFCD02258876 |
InChI Key : | PTARWPNYVATTDE-UHFFFAOYSA-N |
Pubchem ID : | 2737381 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52.17 g (90%) | aluminium trichloride; In carbon disulfide; water; | A. N-(4-Acetyl-3-methylphenyl)acetamide The reaction was run in a 500 mL 3 neck round bottom (RB) fitted with a mechanical stirrer and reflux condenser. To 45 g (301.6 mmol) of 3-methylacetanilide in 240 mL of carbon disulfide under argon at RT was added 38.6 mL (542.8 mmol) of acetyl chloride with stirring. To the solution was then added 145 g (1.09 mol) of aluminum chloride in small portions over a 1 h period. After addition was complete the mixture was refluxed for 1 h and then allowed to cool and stand for 1 h. The supernatant carbon disulfide layer was decanted off and the very dark viscous lower layer was poured into a mixture of cracked ice and hydrochloric acid. The precipitate was collected and washed with 1 L of water. The solid was dried under high vacuum for 30 h at RT to provide 52.17 g (90%) of title amide in the form of a light tan solid which is used as the crude material in the following reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With lithium perchlorate;gallium(III) triflate; In nitromethane; at 50℃; for 24.0h;Product distribution / selectivity; | The acylation reaction was conducted as described in Example 1 using various anilides and acylating agents. Ga(OTf)3 and Ga(ONf)3 were used as the catalyst. The results are shown in Table 6. [14.1] In this Table 6, reaction products 2a, 2b, 2c, 2d, 2e, 2f, 2i, 2j and 2k were all products in which the acyl group R4-CO- is bonded to the p- (para) position of the benzene ring. Meanwhile, reaction product 2g was obtained as a mixture with 2g' as shown below. [15.1] Further, reaction products 2h and 21 indicate the following products. [15.2] In all entries, the reaction proceeded smoothly in the presence of a catalytic amount of the gallium compound in MeNO2-LiClO4 and showed excellent yield. Acetoanilide (1a), as well as benzanilide (1b) reacted with certain acetic anhydrides to obtain the corresponding acylation product in high yield. Further, N-methanesulfonyl (MS)-N-methylaniline (lc) was reacted with acetic anhydride in the presence of 10 mol% of Ga(OTf)3 to obtain acylation product 2e in a 97% yield. Some o- and m-substituted aniline derivatives also provided acylation products in high yield in the presence of a catalytic amount of Ga(OTf)3 or G(ONf)3. In the benzoylation reaction, 1c and 1k reacted smoothly with benzoyl chloride in 1,2-dichloroethane under reflux for 24 hours to give the desired products (2m and 2n) in high yield. When carboxylic acid was used as the acylating agent, the desired acylation product (2b) was obtained in excellent yield without the formation of a trifluoroacetylation adduct, by adding trifluoroacetic anhydride. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48.8% | To a suspension of compound B (500 g, 3 mol in theory) in CH2CI2 (6 L) cooled to 0-10 0C was added AICI3 (1400 g, 10.5 mol) portionwise. The mixture turned clear and a few minutes later turned cloudy. AcCI (282.6 g, 3.6 mol) was added dropwise while keeping the temperature below 20 0C. Then the resulting mixture was stirred at room temperature overnight. TLC (EtOAc: Petroleum ether = 1 :2) indicated the reaction was complete. The mixture was poured carefully into a mixture of cone. HCI (1 L) and ice (2 Kg) with strong stirring. The solid was collected via filtration to give compound C (100 g). The organic layer was separated from the filtrate, washed with water (1.5 L) and brine, dried over Na2SO4 and concentrated until about 150 mL of CH2CI2 was left. The mixture was filtered to give compound C (180 g). The total yield is 48.8%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With sulfur; at 135℃; for 6.0h;Inert atmosphere; | 4-Acetamido-2-methylacetophenone (40b, 0.96 g, 5.0 mmol, 1.0 eq)was dissolved in morpholine (0.9 mL) and sulfur (0.32 g, 10.0 mmol,2.0 eq) were added. Afterwards the mixture was stirred at 135 C for6 h. The reaction was stopped by pouring the warm mixture in warmethanol (2 mL). After cooling to 0 C for 16 h, a precipitate was formed,which was filtered off and recrystallized in cold ethanol. Yield 0.76 g,52%. 1H NMR (250 MHz, DMSO-d6) δ=9.82 (s, 1H), 7.37 (dd,J=13.4, 5.1 Hz, 2H), 6.96 (d, J=8.3 Hz, 1H), 4.33-4.26 (m, 3H), 4.13(s, 2H), 3.75-3.68 (m, 2H), 3.60 (dd, J=8.4, 4.1 Hz, 3H), 3.55-3.49(m, 3H), 2.20 (s, 3H), 2.03 (s, 3H). 13C NMR (75 MHz, DMSO-d6)δ=199.43, 168.32, 137.73, 136.27, 129.70, 127.34, 120.77, 116.82,65.85, 65.80, 56.15, 50.53, 49.73, 46.30, 24.01, 19.52, 18.60. |
45.2% | With sulfur; at 110 - 130℃; | A mixture of compound C (96 g, 0.5 mol), morpholine (48.5 g, 0.558 mol) and sulfur (17.9 g, 0.558 mol) was heated to 110-13O0C and stirred overnight. TLC (EtOAc: Petroleum ether = 1 :2) indicated the reaction was complete, the mixture was powered into hot water (70-80 0C, 1 L) with strong stirring. A few minutes later, some solid deposited. The solid was colleted via filtration to give crude compound D, which was re-crystallized from EtOH (150 ml) at 70~80C to give compound D (66 g, 45.2%). <n="39"/>1H NMR (400 MHz, CDCI3): δ 7.443 (s, 1 H), 7.254-7.131 (m, 2H), 7.131-7.080 (d, 1 H), 4.440- 4.340 (t, 2H), 4.179 (s, 2H), 3.818-3.786 (t, 2H), 3.497 (s, 4H), 2.231 (s, 3H), 2.187 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4% | With trifluorormethanesulfonic acid; at 180℃; for 6.0h; | 4-Acetamido-2-methylacetophenone (Aldrich, 5.0 g, 26.1 mmol) was melted at 180 0C in an open round bottled flask. To the stirred homogenous solution was added triflic acid (Fluka, 250 μl, 2.9 mmol). After Ih another 250 μl of triflic acid were added. The thick brown mixture was allowed to cool after 5 h. The product was purified by preparative HPLC and obtained in 570 mg after lyophilisation, 4 % yield. The structure was confirmed by NMR analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | Step l (E)-l-(4-amino-2-methyIphenyI)-3-(3-methyI-lH-iϖdazol-5-yl)prop-2-en-l-one[00217] To a solution of KOH (1.5 g, 26 mmol) in 20 mL ethanol were added 3 -methyl- IH- indazole-5-carbaldehyde (see Note 1 for synthesis) (0.850 g, 5.3 mmol) and commercially available <strong>[34956-31-5]N-(4-acetyl-3-methylphenyl)acetamide</strong> (1.0 g, 5.3 mmol). The reaction mixture was heated to 80 C for 24 hours and then cooled down to room temperature. After acidification with IN HCl, the mixture was brought to pH 8 with saturated aqueous NaHCO3 and extracted twice with ethyl acetate (2 x 100 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The product was purified by SiO2 flash chromatography (60:40 to 50:50 hexanes/ethyl acetate) to afford (E)-I -(4-amino-2- methylphenyl)-3-(3-methyl-lH-indazol-5-yl)prop-2-en-l-one (0.500 g, 32%). 1H NMR (400 MHz, d6-DMSO): δ 12.8 (s, IH), 8.12 (s, IH), 7.81 (dd, IH), 7.78 (d, IH), 7.61 (d, 2H), 7.48 (d, IH), 6.45 (m, 2H), 5.88 ( br s, IH), 3.06 (s, 3H), 2.42 (s, 3H); MS (EI) for C18HnN3O: 292.3 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[00607] To a mixture of <strong>[34956-31-5]N-(4-acetyl-3-methylphenyl)acetamide</strong> (1.3g, 7.0 mmol) and NaOH (1.4 g, 36 mmol) in 25 mL of absolute EtOH was added 4-hydroxy-3-methylbenzaldehyde (1.0 g, 7.3 mmol). The reaction mixture was stirred at room temperature for 18 hr. 5 mL of water was added and the reaction mixture was acidified with concentrated HCl to pH 5-6. The aqueous layer was extracted with two 25 mL portions of EOAc, and the layers were separated. The organic layer was dried with Na2SO4, filtered and concentrated under reduced pressure. The resulting product was submitted to the next step without further purification. MS (EI) for Ci9Hi9NO3: 310 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | [00248] To a round bottomed flask was added EtOH (30 mL) and potassium hydroxide (6.0 g, 109.5 mmol). The mixture was stirred until homogeneous before adding commercially available 4-hydroxy-3-methyl benzaldehyde (3.Og, 21.9 mmol) and commercially available 4- acetamido-2-methyl acetophenone (4.2 g, 21.9 mmol). The reaction was heated to 80 0C overnight, cooled to rt, and concentrated via rotary evaporation. The solid was dissolved in H2O and neutralized with IN HCl until pH =7. The aqueous mixture was extracted 5 X with EtOAc. The combined EtOAc layers were concentrated and column purified on silica gel (1 : 1 EtOAc: Hexanes) to afford (E)-I -(4-amino-2-methylphenyl)-3-(4-hydroxy-3-methylphenyl) prop-2-en-l -one (2) (3.1 g, 55% yield).1H NMR (400 MHz, d6-DMSO) δ 7.64 (dd, 2H), 7.37 (s, 2H), 6.81 (d, IH), 6.42 (m, 2H), 5.87 (d, 2H), 2.38 (d, 4H), 2.15 (s, 2H); MS (EI) for Ci7H17NO2: 268.2 (MH+). |
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