Checked by B. L. Chenard and Bruce E. Smart.
1. Procedure
A.
3,3-Bis(methylthio)-1-(2-pyridinyl)-2-propen-1-one. A
3-L, three-necked flask is equipped with an
efficient mechanical stirrer,
pressure-equalizing dropping funnel with needle valve, and a
reflux condenser fitted with a nitrogen gas inlet tube that is attached to a mineral oil bubbler. The system is flushed with
nitrogen, and while the system is maintained under a static pressure of
nitrogen, the flask is charged with
1000 mL of dry tetrahydrofuran (Note
1) and
96.5 g (0.86 mol) of potassium tert-butoxide (Note
2). Freshly distilled
2-acetylpyridine (50.0 g, 0.41 mol) (Note
3) is then added dropwise over a period of 5–10 min (Note
4). To the resulting reaction mixture
32.7 g (0.43 mol) of carbon disulfide is added over a period of 30–35 min. After the addition is completed,
122.1 g (0.86 mol) of methyl iodide is added over 1 hr to the viscous, heterogeneous orange reaction mixture. After the tan reaction mixture is stirred for 12 hr at room temperature, it is poured into 2 L of iced water and allowed to stand for 4 hr. The solid that precipitates is collected by filtration and air-dried to give
56 g (
61%) of yellow crystals, mp
106–107°C. The filtrate is diluted with water to a total volume of 4 L, and chilled to afford an additional
16.5 g (
18%) of product, mp
104–107°C (Note
5).
B.
4'-(Methylthio)-2,2' : 6',2''-terpyridine (Note 6). A
1-L, three-necked round-bottomed flask fitted with a mechanical stirrer and a gas inlet tube is flushed with
nitrogen and charged with
500 mL of anhydrous tetrahydrofuran and
22.4 g (0.20 mol) of potassium tert-butoxide. Freshly distilled
2-acetylpyridine (12.1 g, 0.10 mol) (Note
3) is added, the solution is stirred for 10 min, and
22.5 g (0.1 mol) of 3,3-bis(methylthio)-1-(2-pyridinyl)-2-propen-1-one is then added. The mixture is stirred for 12 hr at room temperature, during which time it turns bright red and a red solid precipitates (Note
7). The mixture is next treated with
77 g (1.0 mol) of ammonium acetate and
250 mL of glacial acetic acid. A distillation head fitted with a
thermometer is attached to the flask and the
tetrahydrofuran is removed by distillation over a 2-hr period. The residual brown solution is chilled to 15°C, treated with 400 g of ice, and allowed to stand for 3 hr. Water (400 mL) is added, the mixture is chilled to 15°C, and the gray material that precipitates is collected by filtration, washed with iced water (3 × 200 mL), and air-dried. The crude product is taken up in
250 mL of boiling ethanol and filtered. The filtercake is rinsed with 50 mL of hot
ethanol, and the hot filtrates are combined, diluted with 150 mL of water, concentrated to a volume of 400 mL, and allowed to cool to room temperature. After the mixture is thoroughly chilled in an
ice bath, the precipitate is collected by filtration, washed with
50% aqueous ethanol, and dried under reduced pressure (23°C, 0.1 mm) to give
20.6–21.4 g (
74–77%) of
4'-(methylthio)-2,2' : 6',2''-terpyridine as gray needles, mp
118–119°C (Note
8). This material is sufficiently pure for use in the following step.
C.
2,2' : 6',2''-Terpyridine.
A 1-L, four-necked flask equipped with a mechanical stirrer, pressure-equalizing dropping funnel, thermometer, and a condenser fitted with a nitrogen gas inlet tube is flushed with
nitrogen and charged with
300 mL of ethanol,
5.0 g (0.018 mol) of 4'-(methylthio)-2,2' : 6',2''-terpyridine and
42.8 g (0.180 mol) of finely ground nickel chloride hexahydrate (Note
9). The resultant green heterogeneous mixture is chilled in an ice bath while the system is maintained under a static pressure of nitrogen. To this chilled (0–5°C) mixture, a solution of
20.4 g (0.54 mol) of sodium borohydride in 128 mL of 40% aqueous sodium hydroxide is added dropwise over 4 hr (Note
10). After the addition is completed and the evolution of
hydrogen subsides, the dark reaction mixture is refluxed for 12 hr. The hot mixture is then filtered through a Celite pad, and the pad is washed with hot
ethanol (3 × 100 mL). The filtrates are combined and evaporated to dryness under reduced pressure to yield a gray solid residue (Note
11). This solid is suspended in 300–400 mL of water and chilled in an ice bath for 4 hr. The cold suspension is filtered and the gray solid is air-dried. The crude product is taken up in
100 mL of boiling hexane and filtered. The filtrate is concentrated to 50 mL, chilled in an ice bath, and filtered to give
2.48–2.53 g (
59–60%) of
2,2' : 6',2''-terpyridine as cream-colored prisms, mp
84–86°C [lit.
2 mp
85–86°C] (Note
12) and (Note
13). The mother liquor is concentrated to 10 mL to give a second crop of
0.37–0.40 g (
8.8–9.5%), mp
81–84°C.
2. Notes
3. The checkers obtained
2-acetylpyridine from the Aldrich Chemical Company, Inc. The submitters thank
Reilly Tar & Chemical Corp. for a generous gift of 2-acetylpyridine used in their work.
4. A light yellow solid precipitates during this addition.
5. The product is pure by
1NMR (CDCl
3) δ: 2.55 (s, 3 H), 2.65 (s, 3 H), 7.40 (d of d of d, 1 H,
J = 1.5, 5.6, 7.5), 7.65 (s, 1 H), 7.85 (d of t, 1 H,
J = 7.5, 2.0), 8.20 (d of t, 1 H,
J = 7.5, 1.5), 8.65 (d of m, 1 H
J = 7.5); IR (KBr) cm
−1: 1484, 1471. Analytically pure material, mp
108–109°C, may be obtained by recrystallization from
ethanol.
6. Recently, it has been shown that this product may be prepared without isolation of the precursors obtained in Step A.
3
7. This solid is the potassium salt of the enedione intermediate.
8. The checkers also obtained material with mp
116–118°C. The submitters report product of unspecified purity with mp
120–122°C. The material obtained by the checkers shows the following
1H NMR (CDCl
3) δ: 2.0 (s, impurity), 2.67 (s, 3 H), 7.30 (d of d of d, 2 H
J = 1.8, 5.6, 8.0), 7.80 (d of t, 2 H,
J = 1.8, 8.0), 8.35 (s, 2 H), 8.4–8.78 (m, 4 H). Mass spectrum
m/e calculated: 279.0830. Found: 279.0815. IR (KBr) cm
−1: 1558, 1390. The combustion analyses for the products obtained by the checkers were within accepted limits for H, but off about 2% for C, and 0.6–0.8% for N.
10. This reaction, which generates
nickel boride,
4 is exothermic and evolves
hydrogen. Frothing is prevented by keeping the reaction mixture at 0–5°C during addition of the
sodium borohydride.
11. The submitters report obtaining tan material.
12. This material is analytically pure. Anal. calcd. for C
15H
11N
3:C, 77.23;H, 4.75; N, 18.01. Found C: 76.82; H, 4.69; N, 18.17. The product shows
1H NMR (CDCl
3) δ: 7.33 (d of d of d, 2 H
J = 1.5, 5.0, 8.0), 7.86 (d of t, 2 H,
J = 2.0, 8.0), 7.96 (t, 1 H,
J = 8.0 H), 8.45 (d, 2 H
J = 8.0), 8.62 (d, 2 H,
J = 8.0), 8.71 (d of m, 2 H).
13. The submitters report that
4'-(methylthio)-2,2' : 6',2''-terpyridine also can be conveniently reduced to
2',2'' : 6',2''-terpyridine with
Raney nickel in
ethanol. The checkers found, however, that this procedure invariably gave product contaminated with
4'-ethoxy-2,2' : 6',2''-terpyridine. Raney
nickel which was exhaustively washed with water to remove base still gave 15% of this by-product.
3. Discussion
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
sodium/benzophenone
nickel boride
2',2'' : 6',2''-terpyridine
6-bromo-2,2'-dipyridyl
ethanol (64-17-5)
acetic acid (64-19-7)
ammonium acetate (631-61-8)
hydrogen (1333-74-0)
sodium hydroxide (1310-73-2)
nitrogen (7727-37-9)
copper (7440-50-8)
nickel (7440-02-0)
iodine (7553-56-2)
pyridine (110-86-1)
sodium (13966-32-0)
carbon disulfide (75-15-0)
ferric chloride (7705-08-0)
Methyl iodide (74-88-4)
nickel chloride hexahydrate (7791-20-0)
Tetrahydrofuran (109-99-9)
lithium aluminum hydride (16853-85-3)
2-Bromopyridine (109-04-6)
hexane (110-54-3)
sodium borohydride (16940-66-2)
2,2'-bipyridyl (366-18-7)
TERPYRIDINE
2-acetylpyridine (1122-62-9)
3,3-bis(methylthio)-1-(2-pyridinyl)-2-propen-1-one (78570-34-0)
2,6-dibromopyridine (626-05-1)
2-lithiopyridine
potassium tert-butoxide (865-47-4)
2,2' : 6',2' -TERPYRIDINE,
2,2' : 6',2''-Terpyridine (1148-79-4)
4'-(Methylthio)-2,2' : 6',2''-terpyridine (78570-35-1)
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