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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Synonyms: 3,4-Dihydro-1(2H)-naphthalenone
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CAS No. : | 529-34-0 |
Formula : | C10H10O |
M.W : | 146.19 |
SMILES Code : | O=C1CCCC2=C1C=CC=C2 |
Synonyms : |
3,4-Dihydro-1(2H)-naphthalenone
|
MDL No. : | MFCD00001688 |
InChI Key : | XHLHPRDBBAGVEG-UHFFFAOYSA-N |
Pubchem ID : | 10724 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H312 |
Precautionary Statements: | P264-P270-P301+P312-P312-P330-P501 |
* 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 |
---|---|---|
84% | With N-Bromosuccinimide; dibenzoyl peroxide; In benzene; for 4h;Reflux; Inert atmosphere; | General procedure: A benzene suspension (30 mL) of 1-tetralone 4, 11, 16 (1.0 equiv), N-bromosuccinimide (NBS) (2.2 equiv) and (PhCOO)2 (5 mol percent) was refluxed under Argon atmosphere for 4 h and then cooled to 20 °C. To the reaction mixture was added triethylamine (1 mL) and the solvent was removed in vacuo. The reaction mixture was diluted with water and extracted with CH2Cl2 (3.x.25 mL). The combined organic layers were dried (Na2SO4), filtered and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (silica gel, heptane/EtOAc) to give 5, 12 and 17. |
59% | With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In benzene; for 4h;Reflux; Inert atmosphere; | A benzene suspension (30 mL) of 1-tetralone (1.8mL, 13.7 mmol), N-bromosuccinimide (NBS) (4.9 g, 27.5 mmol), and AIBN (0.1 g, 5 molpercent) was refluxed under argon atmosphere for 4 h, and then cooled to 20 . To the reaction mixture was added triethylamine (2 mL) and the solvent was removed in vacuo, added by water and extracted with CH3Cl. The organic layer was dried over MgSO4 and concentrated in vacuo. The product was purified by flash column chromatography using hexane and EtOAc to give 2-bromo-1-naphthol as white solid (1.8 g, 59percent), 1H NMR (300MHz, CDCl3) d 8.24?8.21 (m, 1H), 7.77?7.73 (m, 1H),7.51?7.43(m, 3H), 7.28 (d, J = 8.8 Hz, 1H),5.96 (s, 1H); 13C NMR (75 MHz, CDCl3) d 148.1, 133.7,128.3, 127.5, 126.8, 126.1, 124.3, 122.2, 121.3, 103.9; GC-MS m/z 222, 224 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step A Alkylation of 3-Amino-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one 3-Amino-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one was prepared from alpha-tetralone using the methods described in Armstrong et al. Tetrahedron Letters. 1994, 35, 3239. The following compounds were as prepared by this procedure for use in the following steps: 5-methyl-3-amino-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one (from 4-methyl-alpha-tetralone (Aldrich)); and 5,5-dimethyl-3-amino-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one (from 4,4-dimethyul-alpha-tetralone (Aldrich)). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; paraformaldehyde; In ethanol; water; | Step D 2-(N-Benzylmethylamino)methyl-6-fluoro-3,4-dihydro-2H-naphthalene-1-one hydrochloride To an ice-cooled solution of N-benzylmethylamine (5.67 cm3) in ethyl alcohol (60 cm3) was added hydrochloric acid (5 M, 10 cm3). <strong>[703-67-3]6-Fluoro-3,4-dihydro-2H-naphthalene-1-one</strong> (6.00 g) and paraformaldehyde (1.32 g) were then added and the resulting mixture was stirred and heated to reflux for 4 h. Upon cooling, the alcohol was removed under reduced pressure and water (100 cm3) was added. The remaining tetralone was extracted into diethyl ether (100 cm3) and the aqueous mixture was then extracted further with dichloromethane (2*100 cm3). The combined extracts were dried (Na2SO4) and concentrated under reduced pressure. Trituration with diethyl ether and filtration provided the title compound (3.18 g) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; thionyl chloride; In tetrahydrofuran; hexane; toluene; | 5.7 g (31.4 mmol) of <strong>[117738-77-9]2-chloro-4-cyano-benzoic acid</strong>, which was prepared by oxidation of 3-chloro-4-methyl-benzonitrile (according to Chem. Ber. 1936, 69, 537, the disclosure of which is incorporated herein by reference), were dissolved in 300 ml toluene, and 10.25 g (86.2 mmol) thionyl chloride were added. After 4 hours heating with reflux the same amount of thionyl chloride was added and heating was continued overnight. The solvent was removed under reduced pressure, the residue dissolved in 100 ml toluene, and again it was concentrated in vacuo to leave the crude acid chloride as a yellow oil. Yield: 4.1 g (65%) A solution of 0.98 g (3.96 mmol) of the tetralone 98 and 3.3 ml dry pyridine in 33 ml dry THF was cooled with ice, and a solution of 1.0 g (5.0 mmol) of the crude 2-chloro-4-cyanobenzoyl chloride in 33 ml dry THF was added dropwise. The mixture was warmed slowly to room temperature, stirred over night, and poured into ice-cold water. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium bicarbonate and with brine, successively, and dried over sodium sulfate. The product was concentrated under reduced pressure, and the residue was stirred with hexane to give the crystalline nitrile (280), which was filtered and dried in vacuo at 50 C. Yield: 1.5 g (92%) of beige crystalline solid, m.p. 173-175 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
< 0.1 mmol | With transaminases XP_001209325; rac-methylbenzylamine; In aq. phosphate buffer; at 28℃; for 24h;Enzymatic reaction; | General procedure: In a final volume of 0.25 μl buffered with 100 mM potassium phosphate (KPi) at pH 7.5 equimolar amounts of 70 mM of amino donor and 70 mM of ketone substrate were reacted in the presence of 0.1 ml CFE of a transaminase at 28 C. for 24 h. CFE comprising transaminases XP-001209325, AAN21261 and ABN35871, respectively, was incubated with benzylacetone and α-methylbenzylamine yielding 4-phenyl-2-butylamine and acetophenone; propiophenone and α-methylbenzylamine yielding α-ethylbenzylamine and acetophenone; 1-indanone and α-methylbenzylamine yielding 1-aminoindan and acetophenone; 1-tetralone and α-methylbenzylamine yielding 1-aminotetralin and acetophenone; 2-tetralone and α-methylbenzylamine yielding 2-aminotetralin and acetophenone; butanone and α-methylbenzylamine yielding 2-aminobutane and acetophenone; and 3,3-dimethyl-2-butanone and α-methylbenzylamine yielding 3,3-dimethyl-2-aminobutane and acetophenone, respectively. The reactions were stopped by addition of 0.75 ml stopping reagent (50% (v/v) acetonitrile in H2O containing 0.1% (v/v) formic acid) to 0.25 ml reaction volume. The product concentrations and enantiomeric excesses were analysed by HPLC as described in the general part. The results of the HPLC analysis are given in table 6. Further CFE comprising transaminase YP-955297 was incubated with propiophenone and α-methylbenzylamine yielding α-ethylbenzylamine and acetophenone. The reaction was stopped by addition of 0.75 ml stopping reagent (50% (v/v) acetonitrile in H2O containing 0.1% (v/v) formic acid) to 0.25 ml reaction volume. The product concentration and enantiomeric excess was analysed by HPLC as described in the general part. After 24 h incubation at 28 C. 0.87 mmol/l (R)-α-ethylbenzylamine was obtained with an e.e. of 99%. The above results show transaminases XP-001209325 and YP-955297 are highly selective (R)-transaminases. Further it becomes clear that XP-001209325 has a different substrate spectrum than the transaminases AAN21261 and ABN35871: 4-phenyl-2-butylamine was formed in significant concentrations by XP-001209325 but not by transaminases AAN21261 and ABN35871 (table 6). Additionally XP-001209325 produced enantiomerically enriched (R)-2-aminobutane from 2-butanone, while ABN35871 delivered enantiomerically enriched (S)-2-aminobutane (table 6). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With zirconium(IV) chloride; In toluene; at 20 - 50℃; for 2h; | To a reactor equipped with reflux condenser, dropping funnel and thermo-pocket, was charged 2-(4-(4-chlorophenyl)-1-hydroxy cyclohexyl)-3,4-dihydronaphthalen-1-(2H)-one (5.0 g, 0.04 mol) and dissolved in toluene (50 mL) at room temperature. To the above solution was added ZrCl4 (0.33 g, 1.4 mmol) and the reaction mass was stirred at 50 °C for 2 h. The reaction mass showed complete conversion of starting material to a-tetralone and 4-(4- chlorophenyl) cyclohexanone in 1 :1 ratio and no olefin product could be identified and isolated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With toluene-4-sulfonic acid; In toluene; at 60℃; for 6h; | 2-(4-(4-chlorophenyl)-1-hydroxycyclohexyl)-3,4-dihydronaphthalen-1-(2H)-one (12.0 g, 0.0.034 mol) was charged in a reactor equipped with overhead stirrer, reflux condenser and thermo-pocket. Toluene (200 mL) was added to suspend the material and p-toluene sulfonic acid (0.3 g, 2.5 mol percent) was added to the reaction mass which was then heated to 60 °C and stirred for 6 h. Progress of reaction was monitored on TLC. After completion of reaction, reaction mass was cooled to RT and solvent was evaporated under pressure to obtain residue. To the residue, was added ethyl acetate (150 mL) and washed with sat. NaHC03 soln. and brine followed by evaporation of solvent to give crude product which was further recrystallised from methanol to afford white solid compound (5.3 g, 50 percent yield). The mother liquor obtained after re-crystallisation was subjected to GC analysis wherein both a-tetralone and 4-(4-chlorophenyl) cyclohexanone were identified to be present in approx. 1 : 1 ratio (by respective retention times and AUCs in the mother liquor) and in 50 percent yield. GC retention time: a-tetralone (XII): 17.21 min (Area percent : 46) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridoxal 5'-phosphate; recombinant ω-transaminase from Burkholderia vietnamiensis G4; In aq. buffer; at 37℃; for 12h;pH 7.4;Resolution of racemate; Enzymatic reaction; | General procedure: Racemic amine (10 mM, Table 4) was mixed with glyoxylate (10 mM) in 1 ml of phosphate buffer (100 mM, pH 7.4) containing PLP (20 μM). The reaction was started by adding 0.8 mg/ml of HBV-ω-TA, and the mixture was incubated at 37 C for 12 h. The amount and ee value of the residual amino donor were determined according to Section 2.10. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | 13.6 g (561 mmol) of magnesium was added to 1,120 ml of tetrahydrofuran and heated at 50C, and 130.8 g (561 mmol) of the benzene compound of the above formula (14) was added dropwise to the resulting solution over 2 hours. Thereafter, a reaction was carried out at 65C for 1 hour to prepare a Grignard solution. [0100] 1,120 ml of toluene was added to this solution, and 73.8 g (505 mmol) of 1-tetralone was added dropwise to the resulting solution so as to carry out a reaction at 50C for 3 hours. After the end of the reaction, 299 g of 10 % hydrochloric acid was added to carry out a reaction at 30C for 3 hours, the reaction solution was washed in water, the solvent was removed, and 477 ml of methanol was added for recrystallization to obtain a compound represented by the following formula (15) as 107.6 g (379 mmol, yield of 75%) of a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With acetic acid; In ethanol; for 3h;Heating; | alpha-Tetralone (14.6 g, 100 mmol) and 2-naphthyl hydrazinium chloride (19.5 g, 100 mmol) were put in ethanol together with 2-3 drops of acetic acid, followed by boiling and stirring. After boiling for 3 hours, water was added and the resulting solid was filtered and dried to give a brown solid (24 g, 85%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With toluene-4-sulfonic acid; In isopropyl alcohol; for 72h;Inert atmosphere; Reflux; Darkness; | General procedure: Compounds 8a-g and 10a-e were prepared as follows: isopropyl alcohol (20 mL) was added to a mixture of indole (4) (1.172 g, 10 mmol, 1 eq), 1-tetralone (5) (1.33 mL, 10 mmol, 1 eq), N-phenylmaleimide (7) (1.732 g, 10 mmol, 1 eq) and p-toluenesulfonic acid (0.380 g, 2 mmol, 0.2 eq). 9a-g were prepared similarly: isopropyl alcohol (20 mL) was added to a mixture of indole (4) (1.172 g, 10 mmol, 1 eq), 4-chromanone (6) (1.482 g, 10 mmol, 1 eq), N-phenylmaleimide (7) (1.732 g, 10 mmol, 1 eq) and p-TsOH (0.380 g, 2 mmol, 0.2 eq). The reaction mixture was heated at reflux for three days under a nitrogen atmosphere, and in the absence of light. Upon completion, a solid reaction mixture was cooled down and filtered with IPA (15 mL) and water (5 mL). The crude material was triturated with IPA (20 mL) three times in the absence of light to give a solid. If further purification was necessary, recrystallization with a mixture of dichloromethane and pentane was performed. In the case of 6 derivatives (9a-g) solubility was found to be very poor, and thus recrystallization was performed with a mixture of tetrahydrofuran and pentane. Using this procedure 8a-g, 9a-g, and 10a-e were synthesized. |
Tags: 3,4-Dihydronaphthalen-1-one | 3,4-Dihydro-1(2H)-naphthalenone | Benzene Compounds | Aryls | Ketones | Organic Building Blocks | 529-34-0
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H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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