Organic Syntheses, CV 9, 656
Submitted by Plato A. Magriotis and John T. Brown
1.
Checked by Armin Walser, Carl Mason, and David L. Coffen.
1. Procedure
CAUTION! These operations involve reagents and solvents with potentially harmful vapors (Br2, NH3) and therefore should be conducted in an efficient hood. The use of disposable gloves is highly recommended.
A.
1-Bromovinyl phenyl sulfide. A
1-L, round-bottomed flask is equipped with a
1.5-in egg-shaped magnetic stirring bar and a
100-mL, pressure-equalizing, addition funnel fitted with a Claisen adapter that contains a
drying tube and stopper. The flask is charged with
40.8 g (0.30 mol) of phenyl vinyl sulfide (Note
1) and
250 mL of dichloromethane (Note
2). The resulting solution is cooled to 0°C and
49.6 g (0.31 mol) of bromine (Note
3) is added dropwise over approximately 1 hr through the funnel, until a bright red color persists. The intermediate product,
phenylthio-1,2-dibromoethane (Note
4), is then treated at 0°C with
250 mL of aqueous 40% sodium hydroxide followed by
5.1 g (15 mmol, 5 mol%) of the phase-transfer catalyst tetrabutylammonium hydrogen sulfate. Vigorous stirring is continued at ambient temperature for 2–3 hr until TLC (
10% benzene,
90% hexane) indicates that dehydrobromination is complete (Note
5). The organic layer is separated and the aqueous layer is extracted with two
200-mL portions of dichloromethane. The combined organic extracts are washed with a saturated solution of
sodium bisulfite (250 mL), water (250 mL), and
brine (250 mL) and dried over
sodium sulfate. Excess
dichloromethane is removed under reduced pressure on a
rotary evaporator and the resulting dark brown oil is distilled under vacuum (1.5 mm) to provide
51.5–58.0 g (
80–90%) of pure
1-bromovinyl phenyl sulfide as a pale yellow liquid, bp
76–78°C (Note
6) and (Note
7).
B.
Phenylthioacetylene. An oven-dried,
2-L, three-necked, round-bottomed flask is equipped with a
mechanical stirrer (Note
8), an
acetone-dry ice condenser with a drying tube containing
potassium hydroxide pellets, and a
gas inlet. The flask is placed in an
acetone-dry ice bath (−40°C, bath temperature) and
450 mL of anhydrous ammonia (Note
9) is condensed into the flask. Upon addition of a small piece of
sodium metal (ca. 0.6 g) to the liquid
ammonia the characteristic deep blue color develops. A catalytic amount of anhydrous
ferric chloride (0.25 g, 1.5 mmol; 0.3 mol%) is added with continued stirring (Note
10) and the color of the reaction mixture turns gray. The remaining
sodium metal (10.0 g, 0.46 g-atom total) is added in 0.6-g pieces over ca. 1 hr, since the blue color must be discharged before each new addition of
sodium. A gray suspension of
sodium amide is obtained upon completion of this addition. The temperature of the cooling bath is adjusted to −50°C and the gas inlet is replaced with a
250-mL, pressure-equalizing addition funnel containing
49.5 g (0.23 mol) of 1-bromovinyl phenyl sulfide in
100 mL of anhydrous ether (Note
11). This solution is added dropwise to the freshly generated
sodium amide over 20 min, while the temperature of the acetone-dry ice bath is maintained at −50°C. Stirring is continued (Note
8) at this temperature for 0.5 hr, the brown-red reaction mixture is allowed to warm to reflux temperature (−33°C) during 1 hr, and then is recooled to −60°C (bath temperature). Solid
ammonium chloride is added slowly (Note
12) to quench the
sodium phenylthioacetylide, the cooling bath is removed, and the
ammonia is allowed to evaporate. During evaporation,
400 mL of anhydrous ether (Note
13) is added dropwise through the addition funnel to replace
ammonia. The resulting mixture is filtered at ambient temperature and reduced pressure through a coarse, Celite-packed,
fritted-glass filter to remove the inorganic salts that are subsequently washed three times with
50 mL of anhydrous ether. The combined ethereal filtrate and washes are concentrated on a rotary evaporator and the dark brown residue (Note
14) is transferred to a
100-mL, round-bottomed flask fitted with a short-path distillation head. Pure product (Note
15) is distilled at 1.5 mm pressure (bp
48–50°C, (Note
16)) into an
ice-cooled receiver. In this way,
21.6–24.7 g (
70–80% yield) of
phenylthioacetylene (Note
17) is obtained as a pale yellow liquid, which turns brown-red upon storage at −10°C (freezer) within a few hours (Note
18).
Phenylthioacetylene stored under these conditions is stable for several months.
2. Notes
2.
Dichloromethane (A.C.S. certified) was obtained from Fisher Scientific Company and used as received.
3.
Bromine (A.C.S. certified) was purchased from Aldrich Chemical Company Inc., used as received, and measured with a
50-mL graduated cylinder in the
hood.
4. At this point crude
phenylthio-1,2-dibromoethane can be isolated by separation of the organic phase, extraction of the aqueous layer with
dichloromethane, washing of the combined extracts with saturated
sodium bisulfite solution, drying (MgSO
4), and concentration (
95% crude yield):
1H NMR (270 MHz, CDCl
3) δ: 3.75 (dd, 1 H, J = 11.0, 8.6), 3.94 (dd, 1 H, J = 11.0, 5.5), 5.39 (dd, 1 H, J = 8.6, 5.5), 7.20–7.70 (m, 5 H). This dibromide is relatively unstable giving rise to a streak on silica gel TLC (
10% benzene,
90% hexanes; R
f of the streak front is ca. 0.35,
anisaldehyde detection). It has been reported that a 2:1–3:1 ratio of
cis- and trans-2-bromovinyl phenyl sulfide is obtained upon distillation of the above dibromide.
2
5. Neither a streak nor any significant by-product is detected (UV and
anisaldehyde) by TLC analysis (
Merck 0.25-mm thickness silica gel plates with 254 nm UV indicator).
6. Assay of this material by GC/MS (HP 5970 Mass Selective Detector equipped with a 50-m HP-1 capillary column) shows it to be ca. 96% pure (R
t = 3.6 min; 80–280°C, 20°C/min). The spectral and analytical properties are as follows:
1H NMR (270 MHz, CDCl
3) δ: 5.83 (d, 1 H, J = 2.2), 5.93 (d, 1 H, J = 2.2), 7.35–7.55 (m, 5 H); MS m/e (relative intensity) 216 (M
+, 17), 214 (16), 135 (100), 109 (15). Anal. Calcd for C
8H
7BrS: C, 44.67; H, 3.28; S, 14.91. Found: C, 44.30; H, 3.46; S, 15.23.
7. The literature boiling point is reported as
70–73°C (2 mm).
1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) in
ether has been employed to effect this elimination.
3 However, the procedure reported here is more amenable to large scale preparation because of its lower cost.
8. The stirring blade should be glass because
sodium in
ammonia solution attacks Teflon.
9. Commercial anhydrous
ammonia is employed without further drying.
10. Stirring is maintained at a rate such that splattering of the reaction mixture on the upper parts of the flask's side-wall is minimized (see also ref 4, Chapter I, pp 1–4).
11.
Ether is distilled from
sodium-benzophenone ketyl under
argon just prior to use.
12. A total of
35 g of solid ammonium chloride is added in portions of ca. 1 g with a
spatula.
13.
Anhydrous ether (A.C.S. certified) was obtained from Fisher Scientific Company and used as received.
14. TLC analysis (
10% benzene,
90% hexanes) of the crude reaction mixture (95% yield) indicates complete conversion of vinyl bromide (R
f = 0.5) to
phenylthioacetylene (R
f = 0.6). A minor product, which can be purified by flash column chromatography and identified as
cis-1,2-bis(phenylthio)ethylene,
4 5 6 7 8 9 is also detected (R
f = 0.3) in variable amounts (5–15% yield) depending on the run.
15. Assay of this material by GC/MS shows it to be >98% pure (R
t = 3.0 min; 80–280°C, 15°C/min).
16. Four literature boiling points are reported:
78–79°C (7 mm),
5 86–88°C (14 mm),
2 61–62°C (5 mm),
2 and
48°C (0.8 mm).
10
17. Spectral and analytical properties for
phenylthioacetylene are as follows: IR (neat) cm
−1: 3285, 2040, 1585;
1H NMR (270 MHz, CDCl
3) δ: 3.26 (s, 1 H), 7.20–7.50 (m, 5 H), ;
13C NMR (67.8 MHz, CDCl
3) δ: 70.0, 87.0, 126.5, 126.7, 129.2, 131.4; MS m/e (relative intensity) 134 (M
+, 100), 90 (24), 89 (26), 51 (44). Anal. Calcd for C
8H
6S: C, 71.60; H, 4.51; S, 23.89. Found: C, 71.77; H, 4.63; S, 24.31.
Waste Disposal Information
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
Phenylthioacetylene has been prepared by elimination of
thiophenol and dehydrobromination of
cis-1,2-bis(phenylthio)ethylene4,5,6,7,8,9 and
cis-1-bromo-2-phenylthioethylene,
2,11 12 respectively. The latter was obtained by addition of
thiophenol to
propiolic acid in
ethanol and subsequent one-pot
bromine addition, decarboxylative dehalogenation, and careful distillation to remove the trans isomer.
2,11,12 On the other hand,
cis-1,2-bis(phenylthio)ethylene was prepared by double addition of
thiophenol to
cis-1,2-dichloroethylene.
4,5,6,7 Although these procedures can provide useful amounts of
phenylthioacetylene, they were found to be somewhat less satisfactory in our hands as far as operation and/or overall yields are concerned. Furthermore, we have encountered problems with regard to the reproducibility of one-pot dehydrobrominations of
phenylthio-1,2-dibromoethane.
10 13 14 15 However, the stepwise execution of the double dehydrobromination, as described in the modified procedure reported here, provides preparatively useful quantities of
phenylthioacetylene in a practical manner.
A large variety of phenylthio-substituted alkynes can be conveniently prepared from
phenylthioacetylene as the nucleophilic component (Table I).
20 21 22 23 This type of construction is more flexible than the one based on nucleophilic substitution of a terminal alkali metal acetylide on
phenyl benzenethiosulfonate,
phenyl sulfinyl chloride, and/or
diphenyl disulfide.
24,25 Regio- and stereoselective syntheses of functionalized vinyl sulfides
26 27 28 29 30 are accomplished by Pd(0)-catalyzed hydrostannation,
22 hydroboration,
31 treatment with low-valent
tantalum,
32 and stannylcupration
15,33 of 1-phenylthio-1-alkynes. In turn, vinyl sulfides are very useful intermediates in organic synthesis not only as carbonyl-masking moieties,
34 35 36 37 38 but also in a variety of other transformations,
39 40 41 42 43 including the Ni(0)-catalyzed cross-coupling reactions with alkyl, aryl, and alkenyl Grignard reagents.
44 45 46 47 The important role of the phenylthio group and its higher oxidation states in activating and directing olefins in cycloaddition reactions
48 49 50 has been reviewed.
48
TABLE
PREPARATION OF PHENYLTHIO ALKYNES FROM PHENYTHIOACETYLENE1
|
Entry |
Phenylthioalkynea |
Electrophileb |
%Yieldc |
|
1. |
|
1. HCHO |
82 |
2. t-BuMe2SiCI |
2. |
|
HCHO |
86 |
3. |
|
MeI |
89 |
4. |
|
|
70 |
2. NaBH4/CeCl3 |
5. |
|
1. HCHO |
78 |
|
6. |
|
CICO2Et |
85 |
7. |
|
|
75 |
8. |
|
PhI |
73 |
9. |
|
BuI |
80 |
10. |
|
Me3SiCI |
90 |
|
aAll Phenylthio alkyne products exibited spectral properties (1H NMR, IR, and GC/MS) in accord with the assigned structures. bThe electrophile employed in entries 4 and 7 was prepared from glycolic acid by reaction of its bis(tert-butyldimethylsilyl) derivative with oxalyl chloride followed by N,O-dimethylhyroxylamine hydrochloride.51 Entry 8 involved Pd(O)- and Cu(I)-catalyzed coupling. cIsolated yield after preparative TLC, silica flash chromatography, or short-path distillation.
|
Finally, useful stereoselectivities have been recorded for the heteroconjugate addition of organometallic reagents to 1-silyl substituted vinyl sulfones.
52 53 The synthesis of such sulfones can be achieved starting from
phenylthioacetylene.
15,19,54 The synthesis of the dicobalt hexacarbonyl complex
55 and the polymerization of
phenylthioacetylene56 have been described.
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