6-Aminohexanoic Acid → 6-isothiocyanatohexanoyl chloride

An over-dried and nitrogen-cooled two liter round bottom flask was equipped with a nitrogen inlet, a pressure-equalizing dropping funnel, and mechanical stirrer. A mixture of 6-aminocaproic acid (66.02 g, 0.5 moles) in 500 ml of tetrahydrofuran (dried over Linde 4A Molecular Sieves) was added to the flask. After stirring the mixture for 20 minutes under nitrogen, 240 ml of triethylamine (1.7 moles, dried over Linde 4A molecular sieves) was added with stirring. After stirring for 20 minutes, 36 ml of carbon disulfide (0.6 moles) was added dropwise over a 45 minute period. The reaction mixture was stirred overnight and diluted with 250 ml of tetrahydrofuran. Then 225 ml of trimethylsilyl chloride was added dropwise over a 2.5 hour period. A white precipitate formed. The reaction mixture was gently refluxed with stirring for 7 hours. After cooling, the reaction mixture was filtered in the absence of air. The precipitate was washed with dry tetrahydrofuran, and a red-gold filtrate collected. This tetrahydrofuran solution was concentrated in vacuo at room temperature to remove the solvent. The residue was placed in a 500 ml round bottom flask and dissolved in 250 ml of methylene chloride. Thionyl chloride (70 ml) was then added with stirring over a 20 minute period. After stirring overnight, the solvent was removed on a rotary evaporator to give the crude product. This was distilled twice at 110°-115° (0.2 Torr) to give 31 g of 6-isothiocyanatocaproyl chloride having infrared adsorption bands at 4.6-4.8 u (N=C=S) and at 5.5 u (COCl), and n.m.r. resonances (CDCl3 solvent) at 3.4, 2.8 and 1.5 ppm. in structurally consistent area ratios.

1. customAn over-dried
2. temperaturenitrogen-cooled two liter round bottom flask
3. customwas equipped with a nitrogen inlet
4. additionwas added to the flask
5. stirringwith stirring
6. stirringAfter stirring for 20 minutes
7. stirringThe reaction mixture was stirred overnight
8. customA white precipitate formed
9. temperatureThe reaction mixture was gently refluxed
10. stirringwith stirring for 7 hours
11. temperatureAfter cooling
12. filtrationthe reaction mixture was filtered in the absence of air
13. washThe precipitate was washed with dry tetrahydrofuran
14. customa red-gold filtrate collected
15. concentrationThis tetrahydrofuran solution was concentrated in vacuo at room temperature
16. customto remove the solvent
17. customThe residue was placed in a 500 ml round bottom flask
18. dissolutiondissolved in 250 ml of methylene chloride
19. additionThionyl chloride (70 ml) was then added
20. stirringwith stirring over a 20 minute period
21. stirringAfter stirring overnight
22. customthe solvent was removed on a rotary evaporator
23. customto give the crude product
24. distillationThis was distilled twice at 110°-115° (0.2 Torr)

ORD record

ord-5efc1f1eb9b842e0a0674bf7551b4a9d

Source dataset

uspto-grants-1983_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04378428