Hydrochloric Acid → 1-Mesitylhydrazine hydrochloride

Temperature

-5 °C

A 3.0 L, 3-neck round bottom flask equipped with a mechanical stirrer and an addition funnel was charged with concentrated hydrochloric acid (0.125 L) and deionized water (0.100 L). The solution was cooled to −5° C. in an ice/salt water bath, and 2,4,6-trimethylaniline (70 mL, 0.50 mol, 1.0 equiv.) was added dropwise over 30 minutes; during this time a white precipitate formed. The mixture was stirred for an additional 15-20 minutes before 52.5 mL of a 9.5 M aq. solution of sodium nitrite (70 mL, 0.50 mol, 1.0 equiv.) was added dropwise over 30-45 minutes. The resulting brown solution was allowed to stir for 30 minutes before a 3.3 M solution of stannous chloride dihydrate in 1:1 concentrated HCl:H2O (0.455 L, 1.5 mol, 2.5 equiv.) was added over 4 hours with vigorous stirring. (Upon addition of the stannous chloride solution a thick light orange slurry had formed which sometimes caused seizure of the mechanical stirrer. Addition small amounts of deionized water helped to facilitate stirring again.) The mixture was allowed to warm to room temperature and stirred vigorously for 16 hours. The mixture was cooled to 0° C. for 1 hour before filtering through a fine porosity glass fritted buchner funnel, and the collected orange solid washed with brine and diethyl ether. This orange solid was added to a 2-L round-bottom charged with 10 M NaOH(aq) (1.0 L) and diethyl ether (0.700 L) and cooled to −5° C. Once nearly all of the solid had dissolved (ca. 1 h), the organic layer was removed, and the aqueous layer extracted with diethyl ether (2×0.400 L). The combined organic fractions were dried over Na2SO4, filtered into a flame-dried 2.0 L round-bottom flask, placed under an atmosphere of N2(g), cooled to 0° C., and treated with 4 M HCl in 1,4-dioxane (0.125 L). A white precipitate formed, was collected by vacuum filtration, washed with diethyl ether, and recrystallized from 200 proof EtOH to afford the title compound (50 g, 0.27 mol, 54%) as a white powder. 1H NMR (400 MHz, DMSO) δ 9.57 (3H, s, br, NH, varies), 6.89 (s, 2H), 2.33 (s, 6H), 2.21 (s, 3H); 13C NMR (100 MHz, DMSO) δ 138.06, 136.20, 135.01, 129.17, 20.54, 17.95; IR (thin film) ν 3294, 3002, 2964, 2911, 2680, 1564, 1513, 1481, 852, 825, 753 cm−1; HRESI+/TOF-MS calcd for C9H15N2+ [M]+ 151.1230, found 134.0921 for aniline anion radical (134.0975).

1. customA 3.0 L, 3-neck round bottom flask equipped with a mechanical stirrer and an addition funnel
2. customduring this time a white precipitate formed
3. additionwas added dropwise over 30-45 minutes
4. customhad formed which sometimes caused seizure of the mechanical stirrer
5. temperatureto warm to room temperature
6. stirringstirred vigorously for 16 hours
7. temperatureThe mixture was cooled to 0° C. for 1 hour
8. filtrationbefore filtering through a fine porosity glass fritted buchner funnel
9. washthe collected orange solid washed with brine and diethyl ether
10. additionThis orange solid was added to a 2-L
11. additionround-bottom charged with 10 M NaOH(aq) (1.0 L) and diethyl ether (0.700 L)
12. temperaturecooled to −5° C
13. dissolutionOnce nearly all of the solid had dissolved (ca. 1 h)
14. customthe organic layer was removed
15. extractionthe aqueous layer extracted with diethyl ether (2×0.400 L)
16. dry with materialThe combined organic fractions were dried over Na2SO4
17. filtrationfiltered into a flame-dried 2.0 L round-bottom flask
18. temperaturecooled to 0° C.
19. additiontreated with 4 M HCl in 1,4-dioxane (0.125 L)
20. customA white precipitate formed
21. filtrationwas collected by vacuum filtration
22. washwashed with diethyl ether
23. customrecrystallized from 200 proof EtOH

ORD record

ord-b5611efcbeca42e1900b716aa7fecdd5

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501658B2