reaction, also increase the rate of an SN2′ reaction.6 The
greater preponderance of positive charge at the 4-posi-
tion, with subsequent attack of H2O at this position, is
probably a result of instability of the charge in the
2-position, adjacent to the carbonyl group.
14.7, 17.9, 51.3, 98.5, 116.3, 125.8, 128.8, 129.9, 131.8, 132.7,
135.6, 144.2, 148.7, 152.6, 172.0. MS m/z (EI): 414, 412, 410
(M+); 381, 379, 377, 375 (M - Cl); 203, 201 (M - OC6HCH3Cl3,
100). HRMS (CI): MH+, calcd for C16H15Cl4O4 410.9724, found
410.9689. IR (cm-1): OCH3, 2842; CdO, 1703; CdC, 1631. Anal.
Calcd for C16H14Cl4O4: C, 46.64; H, 3.42; Cl, 34.41. Found: C,
46.50; H, 3.40; Cl, 34.50. GC retention time: 46 min.
2-(2′,4′,6′-Tr ich lor op h en oxy)-6-ch lor o-1,4-b en zoq u in o-
n e (8). 2,4,6-Trichlorophenol (2, 0.75 g, 3.80 mmol) was dissolved
in 25 mL of MeOH. To this stirred solution was added 0.40 g
(2.80 mmol) of Ca(OCl)2. The solution was stirred for 15 min.
Ketal 6, which is present at this point, was converted in situ to
8 by the dropwise addition of 5 drops of concentrated HCl in 35
drops of H2O. After being stirred for 30 min, the solution was
filtered and shaken with 25 mL of CH2Cl2 and 50 mL of H2O.
The CH2Cl2 layer was separated, dried over MgSO4, and removed
under vacuum. The gummy residue was heated with 6 mL of
boiling hexane. The hot solution was decanted from insoluble
material and the solvent was removed under vacuum to leave
another gummy solid. As ice-cold MeOH (5-10 mL) was stirred
into the gummy material in an ice bath, 0.41 g of bright-yellow
quinone 8 precipitated. Yield of crude 8: 64%. After recrystal-
lization from CHCl3/hexane (80:20), the yield was reduced to
Exp er im en ta l Section
Ma ter ia ls. 2,4,6-Trichlorophenol (2), calcium hypochlorite,
Ca(OCl)2, Pd(30%)/charcoal, and MeOH (anhydrous) were ob-
tained commercially. Sodium 2,4,6-trichlorophenoxide was pre-
pared by mixing the appropriate amounts of sodium methoxide
and 2,4,6-trichlorophenol in MeOH, followed by removal of the
MeOH under vacuum leaving the dry solid. Sodium 2,4,6-
trichlorophenoxide was identified by comparison of its IR
spectrum with the literature spectrum. 2,4,6-Trichloro-m-cresol
(5) was prepared by passing Cl2 into a solution of m-cresol in
CCl4 until GC and GC-MS analyses showed that the product
was primarily 5. The solvent was then removed under vacuum
and 5 was crystallized by adding ice-cold petroleum ether.
Compound 5 was identified by its mp, 44-46 °C; (lit.7 mp 46
°C).
In str u m en ta tion . Mass spectral data are expressed as m/z
and as relative intensity (%). GC and GC-FTIR analyses were
performed under the following conditions: 25 m column of
internal diameter 0.20 mm with a methyl silicone stationary
phase of 0.33 mm film thickness and programmed from 120 to
220 °C and 10 °C/min.
Rea ction of 2 w ith Ca (OCl)2 in DMF . To 137 mg (0.69
mmol) of 2 in 5 mL of DMF with stirring was added 100 mg of
Ca(OCl)2 (0.70 mmol). After 20 min, 10 mL of H2O and 5 mL of
CH2Cl2 were added. The CH2Cl2 solution was separated and
dried over MgSO4. Yield of 8 by GC, 40%.
Rea ction of 2,4,6,6-Tetr a ch lor o-2,4-cycloh exa d ien on e
(15) an d 2,4,4,6-Tetr ach lor o-2,5-cycloh exadien on e (16) with
Sod iu m 2,4,6-Tr ich lor op h en oxid e in DMF . To a stirred
solution of 80 mg (0.34 mmol) of 15 or 16 in 5 mL of DMF was
added 76 mg (0.30 mmol) of sodium 2,4,6-trichlorophenoxide.
After 20 min, 10 mL of H2O and 5 mL of CH2Cl2 were added
and the organic layer was isolated and dried over MgSO4. The
formation of quinone 8 from either 15 or 16 was confirmed by
its mass spectrum (GC-MS).
1
48%. Mp: 116.5-118 °C. H NMR (300 MHz): δ 5.63 (d, 1H, J
) 0.4 Hz), 6.990 (d, 1H, J ) 0.40 Hz), 7.46 (s, 2H). 13C NMR
(75.4 MHz): 111.2, 129.2, 129.5, 133.3, 133.9, 142.2, 143.7, 154.0,
155.0, 173.2, 184.0. MS m/z (EI): 342, 340, 338, 336 (M+); 305,
303, 301 (M - Cl, 100); 277, 275, 273 (M - Cl, -CO). HRMS
(EI): M+, calcd for C12H4Cl4O3 335.8919, found 335.8915. IR
(cm-1): CO, 1703; CdC, 1646. Anal. Calcd for C12H4Cl4O3: C,
42.65; H, 1.19; Cl, 41.96. Found: C, 42.32; H, 1.48; Cl, 42.28.
GC retention time: 21 min.
2-(3′-Meth yl-2′,4′,6′-tr ich lor oph en oxy)-5-m eth yl-6-ch lor o-
1,4-ben zoqu in on e (9). A 100-mg (0.24 mmol) sample of ketal
7 was added to 14 drops of H2O and 2 drops of concentrated
HCl. THF was then added dropwise with stirring until 7
dissolved. After 4 h, 10 mL of CH2Cl2 and 20 mL of H2O were
added. The solution was shaken vigorously and the CH2Cl2 layer
was separated and dried over MgSO4. Removal of the CH2Cl2
layer gave 39.5 mg of crude 9. Yield: 45%. Recrystallization from
MeOH gave a return of approximately one-half of the 9. Mp:
145.0-145.5 °C. 1H NMR (300 MHz): δ 2.21 (s, 3H), 2.49 (s,
3H), 5.61 (s, 1H), 7.48 (s, 1H). 13C NMR (75.4 MHz): 13.9, 17.9,
110.7, 125.5, 128.9, 129.4, 133.5, 135.9, 138.9, 142.9, 143.5, 154.8,
173.2, 184.0. MS m/z (EI): 370, 368, 366, 364 (M+); 333, 331,
329 (M - Cl, 100); 298, 296, 294 (M - 2Cl). HRMS (EI): calcd
for C14H8Cl4O3 363.9228, found 363.9214. IR (cm-1): CO, 1703;
CdC, 1652. Anal. Calcd for C14H8Cl4O3: C, 45.94; H, 2.20; Cl,
38.74. Found: C, 45.49; H, 2.28; Cl, 39.17. The structure of 9
was also confirmed by X-ray crystallography, performed by
Molecular Structure Corporation, Houston, TX. GC retention
time: 34.7 min.
2-(2′,4′,6′-Tr ich lor op h en oxy)-6-ch lor o-1,4-d ih yd r oqu in o-
n e (10). To a stirred solution of 20 mg (0.53 mmol) of NaBH4 in
12 mL of 95% EtOH was added slowly 50 mg (0.15 mmol) of 8.
After the solution was stirred for 10 min, 12 mL of CH2Cl2 and
25 mL of H2O were added and the solution was shaken
vigorously. The CH2Cl2 layer was separated, dried over MgSO4,
and passed through silica gel. The solvent was removed and the
crude product was chromatographed with silica gel, using CCl4/
CH2Cl2 mixtures. Dihydroquinone 10 (0.35 mg, 0.10 mmol) was
obtained in the CH2Cl2 fraction. Yield: 70%. Mp: 162-164 °C.
1H NMR (300 MHz): δ 5.95 (d, 1H, J ) 2.8), 6.61 (d, 1H, J )
2.8), 7.68 (s, 2H), 8.20 (s, 1H), 8.22 (s, 1H). (H2O appeared in
the acetone-d6 solvent at ∼3.1 ppm.) The peaks at 8.20 and 8.22
ppm were confirmed as hydroxy protons since they disappeared
when D2O was added to the solvent. 13C NMR (75.4 MHz): 101.5,
111.2, 122.4, 130.2, 130.9, 132.1, 136.9, 146.6, 146.9, 150.9. MS
m/z (EI): 344, 342, 340, 338 (M+); 307, 305, 303 (M - Cl); 272,
270, 268 (M - 2Cl); 132, 130 (100). HRMS (EI): calcd for C12H6-
Cl4O3 337.9075, found 337.9071. IR (cm-1): OH, 3485, 3429; Cd
C, 1614. GC retention time: 38 min. Additional confirmation
for the structure of 10 was derived from its oxidation to 8 with
CrO3 in HOAc and H2O.
Rea ction of 2,4,6,6-Tetr a ch lor o-2,4-cycloh exa d ien on e
(15) an d 2,4,4,6-Tetr ach lor o-2,5-cycloh exadien on e (16) with
Sod iu m 2,4,6-Tr ich lor op h en oxid e in MeOH. The reaction
conditions were identical with those described in DMF. The
formation of ketal 6 from either 15 or 16 was confirmed by its
mass spectrum (GC-MS).
2-(2′,4′,6′-Tr ich lor op h en oxy)-4,4-d im eth oxy-6-ch lor ocy-
cloh exa d ien -2,5-on e (6). Ketal 6 is an intermediate in the
synthesis of quinone 8. Ketal 6 could not be isolated by
crystallization and it decomposed and hydrolyzed to 8 when
subjected to silica gel. The presence and structure of 6 were
confirmed by GC (ret. time, 28 min), GC-MS, and GC-FTIR. MS
m/z (EI) 384, 382 (M+); 355, 353, 351 (M - OMe); 320, 318, 316
(M - OMe, -Cl, 100); 189, 187 (M - OC6H2Cl3). IR (cm-1): CH,
3007; CH3, 2950; OCH3, 2836; CdO, 1713; CdC, 1661 and 1620.
2-(3′-Meth yl-2′,4′,6′-tr ich lor op h en oxy)-4,4-d im eth oxy-5-
m eth yl-6-ch lor ocycloh exa d ien -2,5-on e (7). 2,4,6-Trichloro-
m-cresol (15, 0.64 g, 1.55 mmol) was dissolved in 20 mL of
MeOH. To this stirred solution was added 0.32 g (2.24 mmol) of
Ca(OCl2). After 20 min, ketal 7 was isolated by filtration. Crude
7 was dissolved in CH2Cl2 and washed with H2O to remove
inorganic material. The CH2Cl2 solution was dried over MgSO4
and the solvent was removed under vacuum. The resulting solid
(7) was washed with pentane to remove any unreacted starting
phenol. Recrystallization for MeOH gave 0.20 g of 7. Yield: 32%.
Mp: 165-168 °C. 1H NMR (300 MHz): δ 2.09 (s, 3H), 2.49 (s,
3H), 3.15 (s, 6H), 5.3 (s, 1H), 7.47 (s, 1H). 13C NMR (75.4 MHz):
(6) Carey, F.; Sundbery, R. Advanced Organic Chemistry, 3rd ed.;
Plenum Press: New York and London, 1990; p 264
(7) Crowther, H. L.; McCombie, H. J . Chem. Soc. 1913, 103, 536.
J . Org. Chem, Vol. 67, No. 19, 2002 6829