1-Propanone, 3-(dimethylamino)-1-(2-thienyl)-, hydrochloride (1:1)

Following a protocol defined by Robertson [1], a mixture of 2-acetylthiophene (128g, 1000 mmol), dimethylamine hydrochloride (90 g, 1100 mmol), paraformaldehyde (41 g, 1400 mmol), concentrated hydrochloric acid(5 mL) and isopropanol (500 mL) was refluxed for 6 h. After the completion ofthe reaction, the obtained solution was cooled to 0(0.45 mol) of 2-acetylthiophene, 44.7 g (0.55 mol) of dimethylamine hydrochloride and 19.4 g (0.61 mol) of paraformaldehyde were dissolved in 190 ml of isopropanol, and 4.3 ml Concentrated hydrochloric acid, reflux reaction 8h, cooled to room temperature after filtration, filter cake with cold ethanol 50ml washing, drying to get 88.7g white solid, the yield of 92.4percent.[Show Image] 1.1: Preparation of 3-dimethylamino-1-(thiophen-2-yl)-1-acetone;hydrochloride 2-Acetylthiophene (20.0g, 0.16mol), dimethylamine hydrochloride (16.8g, 0.21 mol), paraformaldehyde (9.5g, 0.32mol) and 50mL anhydrous ethanol were placed into a 150mL three-necked bottle, The mixture was added with concentrated hydrochloric acid to reach a pH of 3-4, and heated to reflux for 8h. The reaction was stopped, and the reacton mixture was cooled to room temperature, frozen overnight, and filtrated in vacumm. The filter cake was washed with cold anhydrous ethanol to be white to obtain 31.2g of white crystal with a yield of 89.6percent. MS (m/e): 184.3 (M+1A mixture of 2-acetylthiophene (100 g, 0.79 mol), dimethylamine hydrochloride (84.3 g, 1.03 mol), Para formaldehyde (31.4 g, 0.35 mol) and 35percent w/w hydrochloric acid (2 g, 0.02 mol) in ethanol (130 ml) was refluxed for 8 hours. The mixture was then cooled to about 20-25°C and diluted with ethanol (160 ml) and acetone (745 ml). The mixture was stirred for 2 hours and the solid was collected by filtration to yield 140 g (80percent) of 3-dimethylamino-1-(2-thienyl)-1-propanone hydrochloride as a colorless crystalline solid2-acetyl thiophene (2-acetylthiophene were dissolved in; (50 isopropyl alcohol); IPA 10.0 g, 80mmol), dimethylamine hydrochloride (dimethylamine hydrochloride; 16.14 g, 198mmol, 2.5 eq.), paraformaldehyde (paraformaldehyde; 6.00 g, 199.8 mmol, 2.4 perAmount) and 37percent HCl (3.9 , 39.6 mmol, 0.5 eq.) The mixture100 inAnd heated for 16 hours.The reaction mixture was cooled to room temperature and the solid was filtered and washed with IPA (50 mL).The white solid was dried in vacuo to give the product (13.3 g, 76percent yield).2-acetylthiophene (DX-A 01, 63.1 g, 0.50 mol), dimethylamine hydrochloride (53.0 g, 0.65 mol)Paraformaldehyde (19.8 g, 0.22 mol)And 1 N hydrochloric acid (1 mL) in ethanol (80 mL) was heated and refluxed for 2 hours. This solution was diluted with ethanol (100 mL) and acetone (500 mL)The resulting mixed solution was cooled to 0 ° C. and stirred for 1 hour more.Next, the obtained crystals were separated by filtration under reduced pressure, And washed with ethanol. The washed solid was heated at 60 ° C. for 5 hours, Dried under reduced pressure, 2-thienyl 2-dimethylaminoethyl ketone hydrochloride(DXA 02 · HCl, 75.0 g, 73percent).2-acetylthiophene (DX-A 01, 63.1 g, 0.50 mol), Dimethylamine hydrochloride (53.0 g, 0.65 mol), Paraformaldehyde (19.8 g, 0.22 mol)And 1 N hydrochloric acid (1 mL) in ethanol (80 mL) was heated, And refluxed for 2 hours.This solution was diluted with ethanol (100 mL) and acetone (500 mL)The obtained mixed solution was cooled to 0 ° C., The mixture was further stirred for 1 hour or more.Next, the obtained crystals were separated by filtration under reduced pressure, And washed with ethanol.The washed solid was heated at 60 ° C. for 5 hours, Dried under reduced pressure, 2-thienyl 2-dimethylaminoethyl ketone hydrochloride(DX-A 02 .HCl, 75.0 g, 73percent).To a solution ofTo 37percent HCl (0.60 ml, 19.8mmol, 0.5Equiv) in 2-propanol (73 mL)middleThe stirred solutionPressSequential addition of paraformaldehyde(3.00 g, 95.1 mmol, 2.4 equiv.), DimethylamineHydrochloride(8.07 g, 99.0 mmol, 2.5 eq.), As well2-Acetylthiophene (5.0 g, 39.6 mmol). The cloudy suspension was heated to 70 & lt; 0 & gt; C and gradually turned to a clear homogeneous mixture. Lt; 0 & gt; CAfter about 18 hours a white precipitate had formed. The reaction mixture was cooled to room temperature and the white solid was takenFiltered and washed with ice-cold ethanol (2 x 30 mL). The white solid was dried at 50 & lt; 0 & gt; C in a vacuum ovenDeg.] C for 12 hours to give 6.0 g (69percent) of 1 as a white solid252.4 g (2.0 mol) 2-acetylthiophene are dissolved in 160 ml isopropanol and added with stirring to 60.1 g (2.0 mol) of paraformaldehyde. Then, 163.1 g (2.0 mol) dimethylamine-hydrochloride are added and the mixture is rinsed with another 100 ml isopropanol. The thick suspension obtained is refluxed for about 3 hours. The suspension is diluted with another 400 ml isopropanol and cooled to about 15° C., suction filtered and washed with 400 ml isopropanol in batches; then it is dried overnight at 60° C. in the vacuum drying cupboard, yield 265.6 g (60.4percent of theory), purity >98percent according to NMR.General procedure: Synthesis Procedure C. For the title compounds cannot to be obtained with Procedure A and Procedure B, the iminium salts of the amines (Mannich Reagents) were used [29]. A suspension of substrate (1 mmol) and iminium salts of amine (1 mmol) was stirred in acetonitrile or toluene at room temperature (Scheme 2). Precipitated crude product was recrystallized from appropriate solvents to yield the desired Mannich bases.A. A.

Molecular Weight:219.73
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:219.0484629
Monoisotopic Mass:219.0484629
Topological Polar Surface Area:48.6
Heavy Atom Count:13
Complexity:159
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes