5-(4-Hydroxypiperidino)-2-thiophenecarbaldehyde

5-(4-Hydroxypiperidino)-2-thiophenecarbaldehyde Property

Melting point:

137-139°

Boiling point:

417.8±45.0 °C(Predicted)

Density 

1.321±0.06 g/cm3(Predicted)

storage temp. 

Keep in dark place,Inert atmosphere,Room temperature

form 

powder to crystal

pka

14.77±0.20(Predicted)

color 

Light yellow to Brown

λmax

371nm(MeOH)(lit.)

Safety

HazardClass 

IRRITANT

HS Code 

2934999090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

P330Rinse mouth.

P403Store in a well-ventilated place.

5-(4-Hydroxypiperidino)-2-thiophenecarbaldehyde Chemical Properties,Usage,Production

Synthesis

1. 5-bromothiophene-2-carbaldehyde (42.30 g) was placed in a reactor and an appropriate amount of water was added. 2. 4-hydroxypiperidine (67.30 g, 3 eq.) was added to the reactor and the mixture was stirred under reflux conditions for tens of minutes until overnight. 3. Immediately after completion of the reaction, the reaction mixture was filtered through filter paper, and the filtrate was cooled with water for tens of minutes, followed by chilling with ice for several hours. 4. The precipitated crystals are collected by diafiltration and washed with cold water. 5. 5. The crystals are dried and dissolved in chloroform and the chloroform solution is dried with anhydrous sodium sulfate. 6. The dried solution is filtered through a pad of silica gel and washed with chloroform until the filtrate becomes pale in color. 7. Concentrate the filtrate under pressure until it begins to crystallize, add n-hexane and stir overnight at room temperature. 8. The crystals formed were collected by filtration, washed with hexane and dried under reduced pressure to give 5-(4-hydroxypiperidin-1-yl)-thiophene-2-carbaldehyde (33.00 g, 71%). 9. 5-(4-hydroxypiperidin-1-yl)-thiophene-2-carboxaldehyde (10.56 g) was subjected to a condensation reaction with 3,4-dimethoxybenzyl cyanide (8.86 g) to give (Z)-2-(3,4-dimethoxyphenyl)-3-[5-(4-hydroxypiperidin-1-yl)-thiophen-2-yl]-acrylonitrile (13.50 g, 73%). 10. (Z)-2-(3,4-dimethoxyphenyl)-3-[5-(4-hydroxypiperidin-1-yl)-thiophen-2-yl]-acrylonitrile (20.00 g) was dissolved in chloroform (650 mL), and pyridine (6.41 g) and bromoacetyl bromide (14.13 g) were added and reacted to give bromoacetic acid 1-[5-[(Z)-2-cyano-2-(3,4-di (Z)-2-cyano-2-(3,4-dimethoxyphenyl)-vinyl]-thiophen-2-yl]-piperidin-4-yl ester (23.00 g, 87%). 11. 1-[5-[(Z)-2-cyano-2-(3,4-dimethoxyphenyl)-vinyl]-thiophen-2-yl]-piperidin-4-yl ester of bromoacetic acid (2.30 g) was dissolved in chloroform (100 mL), and piperidine (533 mg) and triethylamine (658 mg) were added and reacted to give 5-(4-hydroxypiperidinyl)-2-thiophenecarboxaldehyde (1.40 g. 60%).

References

[1] Synlett, 1998, # 4, p. 383 - 384
[2] Synthetic Communications, 2000, vol. 30, # 8, p. 1359 - 1364
[3] Patent: EP2218719, 2010, A1. Location in patent: Page/Page column 7-8