Results and Discussion
We initially attempted the reaction of
p-nitrobenzaldehyde with methyl vinyl ketone in the presence of TiCl
4 (1.0 eq) at -78
oC. No reaction occurred (
Table 1, entry 1). However, after adding 20 mol % (0.20 eq) of triethylamine (Et
3N) as a Lewis base, the reaction took place smoothly to give the chlorinated product
1a, rather than
2a and
3a (usually considered the Baylis-Hillman olefin and trisubstituted alkene) as reported by Kataoka and Li [
9,
12], respectively (
Scheme 1,
Table 1, entry 2). By careful investigation, we found that this reaction was very sensitive to the amounts of both TiCl
4 and amines present in the reaction mixture (
Table 1). By means of catalytic amounts of amine and excess amounts of TiCl
4 the reaction proceeded very well. However, using large excesses of amine as a Lewis base, the reaction was completely stopped (
Table 1, entry 6). This result suggested that the amine could coordinate to TiCl
4 and that free TiCl
4 acting as a Lewis acid was required to promote the reaction. The amount of TiCl
4 was also crucial for this reaction because using a catalytic amount of TiCl
4, the reaction became very slow and gave low yields of
1a (
Table 1, entry 7 and 8). The best reaction conditions were found to be the use of 20 mol % of amine as a Lewis base and 1.4 eq of TiCl
4 as a Lewis acid (
Table 1, entry 4).
Table 1.
Reaction Conditions for the Bayliss-Hillman Reaction of p-Nitrobenzaldehyde with Methyl Vinyl Ketone in the Presence of TiCl4 and Et3N
Table 1.
Reaction Conditions for the Bayliss-Hillman Reaction of p-Nitrobenzaldehyde with Methyl Vinyl Ketone in the Presence of TiCl4 and Et3N
Entry | Eq. of Lewis base (Et3N) | Eq. of Lewis acid (TiCl4) | Yielda) [%] 1a |
---|
1 | 0 | 1.4 | 0 |
2 | 0.05 | 1.4 | 60 |
3 | 0.1 | 1.4 | 76 |
4 | 0.2 | 1.4 | 81 |
5 | 1.0 | 1.4 | 45 |
6 | 6.0 | 1.4 | 0 |
7 | 0.2 | 0.4 | 36 |
8 | 0.2 | 0.8 | 54 |
For many arylaldehydes having strongly electron-withdrawing group on the phenyl ring, the reactions proceed quickly to give compounds
1 in high yields using a catalytic amount of Lewis base (20 mol %) at -78
oC (
Scheme 2,
Table 2). However, other arylaldehydes or aliphatic aldehydes needed higher temperatures (‑20
oC) to give the corresponding chlorinated product
1 in high to moderate yields. Moreover, we found that besides triethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and diethylamine were also very effective Lewis bases for this reaction in the presence of TiCl
4 (
Table 2).
All cases shown in
Table 1 only needed a catalytic amount of amine (20 mol %) to bring the reaction to completion in the presence of TiCl
4 (
Table 2). It should be emphasized that in all cases, only one diastereomer was formed during the reaction process based on the
1H-NMR spectral data evidence. Their relative configurations were confirmed as the
syn-form by analysis of the X-ray crystal structure of
1a [
13] (
Figure 1).
Table 2.
Bayliss-Hillman Reaction of Aldehydes with Methyl Vinyl Ketone in the Presence of TiCl4 and 20 mol% of Lewis Base
Table 2.
Bayliss-Hillman Reaction of Aldehydes with Methyl Vinyl Ketone in the Presence of TiCl4 and 20 mol% of Lewis Base
Entry | R | Lewis base | Temp [°C] | Time [h] | Yielda) [%] 1 |
---|
1 | p-NO2-Ph | none | -78 | 12 | - |
2 | p-NO2-Ph | Et3N | -78 | 12 | 81 |
3 | m-NO2-Ph | Et3N | -78 | 12 | 88 |
4 | p-CF3-Ph | Et3N | -78 | 48 | 80 |
5 | Ph | Et3N | -20 | 48 | 80 |
6 | p-Et-Ph | Et3N | -20 | 48 | 72 |
7 | p-Cl-Ph | Et3N | -20 | 48 | 70 |
8 | CH3(CH2)3 | Et3N | -20 | 48 | 45 |
9 | p-NO2-Ph | Et2NH | -78 | 12 | 88 |
10 | Ph | Et2NH | -20 | 48 | 71 |
11 | p-NO2-Ph | DBU | -78 | 12 | 82 |
12 | Ph | DBU | -20 | 48 | 65 |
Figure 1.
Crystal Structure of 1a
Figure 1.
Crystal Structure of 1a
Compound
1 can be easily and completely transformed to the compound
2 [
14] by treating with an excess amount (2.0 eq) of triethylamine or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (
Scheme 3). The purification of
1 by preparative thin layer chromatography (TLC) was noted to also cause the transformation of
1 to
2, therefore quick flash column chromatography is required in order to obtain the pure product
1.
Besides methyl vinyl ketone, acrylonitrile underwent the same reaction to give the corresponding chlorinated product
1h in moderate yield in CH
2Cl
2 at 10
oC for 5 days (
Scheme 4,
Table 3, entries 1 and 2), but at -78
oC, no reaction occurred (entry 3). Raising the reaction temperature to reflux (45
oC) caused a decrease of the yield of
1h (
Table 3, entry 4). On the other hand, using methyl acrylate as a Michael acceptor, only trace amounts of chlorinated product were obtained under similar reaction conditions (
Scheme 5).
Table 3.
Table 3. Bayliss-Hillman Reaction of p-Nitrobenzaldehyde with Acrylonitrilein the Presence of TiCl4 and 20 mol % of Amine as Lewis Base
Table 3.
Table 3. Bayliss-Hillman Reaction of p-Nitrobenzaldehyde with Acrylonitrilein the Presence of TiCl4 and 20 mol % of Amine as Lewis Base
Entry | Amine | Temp
[°C] | Time
[h] | Yielda) [%] |
---|
1 | Et3N | 10 | 5 | 37 |
2 | DBU | 10 | 5 | 50 |
3 | DBU | -78 | 3 | 0 |
4 | DBU | 40 | 3 | 16 |
To the best of our knowledge, this represents a novel Baylis-Hillman reaction system because use of a catalytic amount of amine as a Lewis base has never been reported to date for titanium(IV) chloride promoted Baylis-Hillman reactions. Recently, Aggarwal has reported that using stoichiometric amounts of amine such as DABCO and a catalytic amount of titanium (IV) chloride gave reduced reaction rates, but that use of stoichiometric amounts of amine and a catalytic amount of lanthanide triflates (5 mol%) gave increased rates in the Baylis-Hillman reaction [
7]. Our system shows that using excess amounts of titanium (IV) chloride and catalytic amount of amines, the major reaction products in moderate to high yields are the β-chlorinated compounds
1, which can be readily transformed to the Baylis-Hillman olefin
2. Thus the reaction rate of Baylis-Hillman reaction can be greatly accelerated by means of this reagent system.
We also examined many other metal halides such as PdCl
2, RhCl
3, Cp
2ZrCl
2, ZrCl
4, AlCl
3, TMSCl, SiCl
4, BF
3, BCl
3 and found that BCl
3 and ZrCl
4 also worked as Lewis acids for this reaction, although they are not as effective as TiCl
4. For example, we carried out the Baylis-Hillman reaction using BCl
3 and ZrCl
4 as Lewis acid with Et
3N as a Lewis base under the same reaction conditions as those shown in
Scheme 1. The
syn-chlorinated products can be also obtained (
Scheme 6), but this required longer reaction times (40 h) at -78
oC. These results are summarized in
Table 4.
Table 4.
Baylis-Hillman Reaction of Aldehydes with Methyl Vinyl Ketone in thePresence of BCl3 (1.4 eq.) or ZrCl4 (1.4 eq) and 20 mol % of Et3N
Table 4.
Baylis-Hillman Reaction of Aldehydes with Methyl Vinyl Ketone in thePresence of BCl3 (1.4 eq.) or ZrCl4 (1.4 eq) and 20 mol % of Et3N
Entry | R | Lewis acid | Temp [°C] | Time [h] | Yielda) [%] |
---|
1 | p-NO2-Ph | BCl3 | -78 | 40 | 64 |
2 | m-NO2-Ph | BCl3 | -78 | 42 | 63 |
3 | o-NO2-Ph | BCl3 | -78 | 42 | 58 |
4 | p-CF3-Ph | BCl3 | -78 | 48 | 42 |
5 | Ph | BCl3 | -20 | 48 | 34 |
6 | p-Cl-Ph | BCl3 | -20 | 48 | 45 |
7 | p-NO2-Ph | ZrCl4 | -78 | 48 | 57 |
8 | p-Cl-Ph | ZrCl4 | -78 | 48 | 43 |
In
Scheme 7, we propose a tentative mechanism to explain the formation of product
1. In fact, the reactions of trimethylamine and dimethylamine with titanium (IV) chloride had been investigated by Antler and Laubengayer in 1955 [15a]. Chloride ion was detected although the system was complicated. Based on his findings, Periasamy gave a mechanism for the reaction of tertiary amines with TiCl
4 [15b]. Recently many crystal structures of Ti complexes derived from the reaction of TiCl
4 with amines have been disclosed including cationic Ti complexes [15c,d,e].
The reaction mechanism proposed in
Scheme 7 is based on those previous findings and the results of our own investigations as shown in
Table 1. We believe that amine can strongly coordinate to the Ti metal center of TiCl
4 to give an ionic metal complex containing chloride ion. This reaction is related with the attack of chloride ion on the methyl vinyl ketone in a Michael addition fashion (
Scheme 7). Using BCl
3 or ZrCl
4 as a Lewis acid, the reactions would proceed via the same mechanism. Thus, the formation of chlorinated compound
1 is a major reaction process in the TiCl
4, BCl
3, and ZrCl
4 and Lewis base amine promoted Baylis-Hillman reaction.
Figure 2.
The chiral Lewis bases used for the Bayliss-Hillman reaction
Figure 2.
The chiral Lewis bases used for the Bayliss-Hillman reaction
We also examined the catalytic enantioselective Baylis-Hillman reaction using chiral amines or aminoalcohols as chiral Lewis bases for this reaction (
Scheme 8). The enantiomeric excesses achieved were determined by chiral HPLC analysis of
1a or
2a after treating with DBU or Et
3N. In
Figure 2, we show the chiral Lewis bases used for this reaction. These chiral ligands (
A-
L) were either prepared by us according to the known synthetic methods or purchased from Aldrich. For sterically bulky amines, the reaction is relatively slow and longer reaction times are required, but in all cases, the achieved enantiomeric excesses were only about 10~20%. We believe that this is related to the mechanism shown in
Scheme 7 because the reaction is via separated ionic intermediates and the chiral centers are far away from the aldol reaction center. These results partially support our proposed reaction mechanism (
Scheme 7).
On the other hand, by carrying out this reaction at room temperature (about 20
oC), we confirmed that the elimination product
3 was the only product under the same reaction conditions (
Scheme 9,
Table 5, entries 3-10).
Table 5.
Bayliss-Hillman Reaction of Aldehydes with Methyl Vinyl Ketone in the Presence of 1.4 eq. of TiCl4 and 0.20 eq. of Et3N at Room Temperature
Table 5.
Bayliss-Hillman Reaction of Aldehydes with Methyl Vinyl Ketone in the Presence of 1.4 eq. of TiCl4 and 0.20 eq. of Et3N at Room Temperature
Entry | R | Time [h] | Yielda) (%) 3 |
---|
1 | p-NO2-Ph | 6 | 30b) |
2 | p-NO2-Ph | 6 | 50 |
3 | p-NO2-Ph | 24 | 92 |
4 | o-NO2-Ph | 24 | 86 |
5 | p-CF3-Ph | 24 | 87 |
6 | p-Cl-Ph | 24 | 75 |
7 | m-F-Ph | 24 | 82 |
8 | p-Et-Ph | 36 | 60 |
9 | Ph | 24 | 77 |
10 | CH3(CH2)8 | 24 | 50 |
This reaction was first disclosed by Li and coworkers. They reported that in the presence of stoichiometric or nonstoichiometric TiX
4, compound
3 could be formed in its Z-configuration [
12]. Later we also reported that
3 could be exclusively obtained in the TiCl
4 and chalcogenide promoted Baylis-Hillman reaction at room temperature (20
oC) [
16]. The
Z-configuration has been confirmed by X-ray analysis (
Figure 3) [
16].
Figure 3.
Crystal Structure of 3a
Figure 3.
Crystal Structure of 3a
We now wish to report that in the initial reaction stage, the presence of Lewis base can still significantly speed up this reaction (
Table 5, entry 1 and 2). In order to clarify the formation of
3, we treated
1a and
2a directly with TiCl
4 in dichloromethane at room temperature. We found that
1a can be transformed to
3a within 6 h, whereas the reaction of
2a with TiCl
4 was much slower (
Scheme 10). These results strongly suggest that
3a is derived directly from
1a formed first in the reaction. Thus, we conclude that, at room temperature, the chlorinated products
1 could be formed either in the absence or in the presence of Lewis base, but they are rapidly transformed to the elimination product
3 exclusively.
Experimental Section
General
Melting points are uncorrected. 1H- and 13C-NMR spectra were recorded on a Bruker AMX-300 spectrometer at 300 MHz and 75 MHz, respectively. Mass spectra were recorded by the EI method and HRMS was measured by a Finnigan MA+ mass spectrometer. Organic solvents used were dried by standard methods when necessary. All solid compounds reported in this paper gave satisfactory CHN microanalyses. Commercially obtained reagents were used without further purification. All reactions were monitored by TLC with Huanghai GF254 silica gel coated plates. Flash Column Chromatography was carried out using 300-400 mesh silica gel at increased pressure.
Typical procedure for the preparation of compounds 1a-h and 2a: 3-(Chloromethyl)-4-hydroxy-4-(4'-nitrophenyl)-2-butanone (1a).
To a solution of triethylamine (10.1 mg, 0.1mmol, 14.0 μL) in CH2Cl2(1.3 mL) was added titanium tetrachloride (0.7 mL, 0.7 mmol) at -78 oC. After stirring for 5 min, a solution of p-nitrobenzaldehyde (75.5 mg, 0.5 mmol) in CH2Cl2 (1.0 mL) and methyl vinyl ketone (105.0 mg, 1.5 mmol, 123.0 μL) were added into the reaction solution at -78 oC, respectively. The reaction mixture was kept for 12 h at -78 oC. The reaction was quenched by addition of saturated aqueous NaHCO3 solution (1.0 mL). After filtration, the filtrate was extracted with CH2Cl2 (5.0 mL x 2) and dried over anhydrous MgSO4. The solvent was removed under reduced pressure and the residue was purified by a flash chromatography (silicagel, eluent 1:4 ethyl acetate/petroleum ether) to give compound 1a (105.0 mg, 81%) as a colorless solid, mp 90-91 oC; IR (KBr) ν 1720 cm-1; 1H-NMR (CDCl3, 300 MHz): δ 2.20 (3H, s, Me), 2.93 (1H, br. s, OH), 3.22-3.38 (1H, m), 3.67 (1H, dd, J 11.3, 4.0 Hz), 3.89 (1H, dd, J 11.3, 9.2 Hz), 5.11 (1H, d, J 5.6 Hz), 7.56 (2H, d, J 8.6 Hz, Ar), 8.25 (2H, d, J 8.6 Hz, Ar); MS (EI) m/e 258 (MH+, 0.60), 208 (M+-49, 60), 71(M+-186, 100); Anal. Found: C, 51.64; H, 4.94; N, 5.35%. C11H12ClNO4 requires C, 51.27; H, 4.69; N, 5.44%.
3-(Chloromethyl)-4-hydroxy-4-(3'-nitrophenyl)-2-butanone (1b).
Colorless oil, 113 mg (88%); IR (KBr): ν 1720 cm-1 (C=O); 1H-NMR (CDCl3, 300 MHz): δ 2.20 (3H, s, Me), 2.95 (1H, br. s, OH), 3.20-3.35 (1H, m), 3.66 (1H, dd, J 11.3, 3.9 Hz), 3.89 (1H, dd, J 11.3, 9.3 Hz), 5.13 (1H, d, J 5.6 Hz), 7.54 (1H, t, J 7.9 Hz, Ar), 7.69 (1H, d, J 7.6 Hz, Ar), 8.2 (1H, d, J 7.6 Hz, Ar), 8.25 (1H, s, Ar); MS (EI) m/e 257 (M+, 0.60), 208 (M+-49, 60), 71(M+-186, 100); [HRMS (EI) m/z 239.0353 (M+-H2O). C11H10O3NCl requires M-H2O, 239.0349].
3-(Chloromethyl)-4-hydroxy-4-(4'-trifluoromethylphenyl)-2-butanone (1c).
Colorless oil, 112 mg (80%); IR(KBr) ν 1720 cm-1 (C=O); 1H-NMR (CDCl3, 300 MHz) δ 2.13 (3H, s, Me), 2.65 (1H, br. s, OH), 3.22-3.37 (1H, m), 3.70 (1H, dd, J 10.2, 3.9 Hz), 3.89 (1H, dd, J 10.2, 10.2 Hz), 5.02 (1H, d, J 6.1 Hz), 7.37 (2H, d, J 8.0 Hz, Ar), 7.64 (2H, d, J 8.0 Hz, Ar); MS (EI) m/e 280 (M+, 0.45), 243 (M+-37, 40), 43 (M+-237, 100); [HRMS (EI) m/z 262.0377 (M+-H2O). C12H10OClF3 requires M-H2O, 262.0372].
3-(Chloromethyl)-4-hydroxy-4-phenyl-2-butanone (1d).
Colorless oil: 85 mg (80%); a; IR(KBr) ν 1720 cm-1 (C=O); 1H-NMR (CDCl3, 300 MHz) δ 2.02 (3H, s, Me), 2.45 (1H, br. s, OH), 3.22-3.37 (1H, m), 3.78 (1H, dd, J 10.7, 3.8 Hz), 3.90 (1H, dd, J 10.4, 10.4 Hz), 4.84 (1H, d, J 6.9 Hz), 7.10-7.32 (5H, m, Ar); MS (EI) m/e 212 (M+, 1.05), 163 (M+-49, 60), 107 (M+-105, 100); [HRMS (EI) m/z 212.0594 (M+). C11H13O2Cl requires M, 212.0604].
3-(Chloromethyl)-4-hydroxy-4-(4'-ethylphenyl)-2-butanone (1e).
Colorless solid: 87 mg (72%);; mp 69-71 oC; IR(KBr) ν 1720 cm-1 (C=O); 1H-NMR (CDCl3, 300 MHz) δ 1.21 (3H, t, J 7.7 Hz), 2.02 (3H, s, Me), 2.15 (1H, br. s, OH), 2.63 (2H, q, J 7.7 Hz), 3.22-3.37 (1H, m), 3.80 (1H, dd, J 10.7, 3.8 Hz), 3.90 (1H, dd, J 10.7, 10.7 Hz), 4.82 (1H, d, J 7.2 Hz), 7.10-7.32 (4H, m, Ar); MS (EI) m/e 222 (M+-18, 1.20), 191 (M+-49, 20), 135 (M+-105, 100); [HRMS (EI) m/z 240.0908 (M+). C13H17O2Cl requires M, 240.0917].
3-(Chloromethyl)-4-hydroxy-4-(4'-chlorophenyl)-2-butanone (1f).
Colorless oil: 86 mg (70%); a; IR(KBr) ν 1720 cm-1 (C=O); 1H-NMR (CDCl3, 300 MHz) δ 2.0 (3H, s, Me), 2.50 (1H, br. s, OH), 3.20-3.32 (1H, m), 3.75 (1H, dd, J 10.7, 3.8 Hz), 3.87 (1H, dd, J 10.7, 10.7 Hz), 4.82 (1H, d, J 6.7 Hz), 7.10-7.32 (4H, m, Ar); MS (EI) m/e 246 (M+, 1.20), 121 (M+-125, 20), 91 (M+-155, 100); [HRMS (EI) m/z 246.0210 (M+). C11H12O2Cl2 requires M, 246.0214].
3-(Chloromethyl)-4-hydroxy-4-butyl-2-butanone (1g).
Colorless oil: 43 mg (45%); a; IR(KBr) ν 1720 cm-1 (C=O); 1H-NMR (CDCl3, 300 MHz) δ 0.89 (3H, t, J 7.1 Hz), 1.10-1.60 (6H, m), 2.08 (1H, s, OH), 2.34 (3H, s, Me), 3.0-3.10 (1H, m), 3.60-3.85 (3H, m); MS (EI) m/e 192 (M+, 0.80), 155 (M+-37, 30), 43 (M+-149, 100); [HRMS (EI) m/z 192.0908 (M+). C9H17O2Cl requires M, 192.0917].
Preparation of 2-(chloromethyl)-3-hydroxy-3-(4'-nitrophenyl)-propionitrile (1h).
Colorless oil: 45 mg (37%); IR(KBr) ν 1720 cm-1 (C=O); 1H NMR (CDCl3, 300 MHz) δ 2.50 (1H, s, OH), 3.28 (1H, q, J 6.1 Hz), 3.70 (1H, dd, J 11.3, 4.5 Hz), 3.96 (1H, dd, J 11.3, 5.8 Hz), 7.67 (2H, d, J 8.3 Hz), 8.28 (2H, d, J 8.3 Hz); MS (EI) m/e 240 (M+, 38.75), 205 (M+-35, 30), 152 (M+-149, 100); [HRMS (EI) m/z 240.0310 (M+). C10H9ClN2O3 requires M, 240.0302].
3-[(4'-nitrophenyl)hydroxymethyl]-3-buten-2-one (2a).
A known compound [
9]. Its physical data was comparable to that reported in literature: mp 66‑68
oC;
1H -NMR (CDCl
3, 300 MHz) d 2.36 (3H, s, Me), 3.26 (1H, br. s, OH), 5.68 (1H, s), 6.05 (1H, s), 6.28 (1H, s), 7.56 (2H, d,
J 8.6 Hz, Ar), 8.19 (2H, d,
J 8.6 Hz, Ar).
Typical Procedure for the Preparation of 3-(Chloromethyl)-4-(4'-nitrophenyl)-3-buten-2-one (3a).
To a solution of triethylamine (10.1 mg, 0.1 mmol, 14.0 μL) in CH2Cl2 (1.3 mL) was added 1.0 N titanium tetrachloride (0.7 mL, 0.7 mmol) in CH2Cl2 at room temperature (20 oC). After stirring for 5 min, a solution of p-nitrobenzaldehyde (76 mg, 0.5 mmol) in CH2Cl2 (1.0 mL) and methyl vinyl ketone (105 mg, 1.5 mmol, 123 μL) were added into the reaction solution at room temperature. The reaction mixture was kept for 24 h at room temperature. The reaction was quenched by addition of saturated aqueous NaHCO3 solution (1.0 mL). After filtration, the filtrate was extracted with CH2Cl2 (5.0 mL x 2) and dried over anhydrous MgSO4. The solvent was removed under reduced pressure and the residue was purified by flash silica gel chromatography to give compound 3a (110 mg, 92%) as a colorless solid (eluent: ethyl acetate/petroleum ether=1/8): mp 134-136 oC; IR(KBr) ν 1640 cm‑1 (C=O); 1H-NMR (CDCl3, 300 Hz) δ 2.55 (3H, s, Me), 4.38 (2H, s, CH2), 7.69 (1H, s), 7.75 (2H, d, J 8.6 Hz, Ar), 8.35 (2H, d, J 8.6 Hz, Ar); MS (EI) m/e 239 (M+, 0.40), 222 (M+-17, 40), 115 (M+-124, 100); [Found: C, 54.94; H, 3.92; N, 5.87%. C11H10ClNO3 requires C, 55.13; H, 4.21; N, 5.84%].
3-(Chloromethyl)-4-(2'-nitrophenyl)-3-buten-2-one (3b).
A colorless solid : 103 mg (86%); mp 120-122 oC; IR(KBr) ν 1640 cm-1 (C=O); 1H-NMR (CDCl3, 300 MHz) δ 2.52 (3H, s, Me), 4.23 (2H, s, CH2), 7.64 (1H, td, J 6.4, 1.5 Hz, Ar), 7.72 (1H, d, J 6.7 Hz, Ar), 7.80 (1H, t, J 7.5 Hz, Ar), 8.02 (1H, s), 8.27 (1H, d, 7.5 Hz, Ar); MS (EI) m/e 239 (M+, 60), 222 (M+-17, 50), 115 (M+-124, 50), 43 (M+-196, 100); [HRMS (EI) m/z 239.0351 (M+). C11H10ClNO3 requires M, 239.0349].
3-(Chloromethyl)-4-(4'-trifluoromethylphenyl)-3-buten-2-one (3c).
A colorless solid: 114 mg (87%); mp 43-45 oC; IR (KBr) ν 1640 cm-1 (C=O); 1H-NMR (CDCl3, 300 MHz) δ 2.54 (3H, s, Me), 4.39 (2H, s, CH2), 7.70 (1H, s), 7.60-7.76 (4H, m, Ar); MS (EI) m/e 262 (M+, 100), 193 (M+-69, 70), 183 (M+-79, 50), 115 (M+-147, 40); [HRMS (EI) m/z 262.0381 (M+). C12H10ClF3O requires M, 262.0372].
Preparation of 3-(chloromethyl)-4-(4'-chlorophenyl)-3-buten-2-one (3d).
A colorless solid: 86 mg (75%); mp 87-89 oC; IR (KBr) ν 1640 cm-1 (C=O); 1H-NMR (CDCl3, 300 MHz) δ 2.51 (3H, s, Me), 4.42 (2H, s, CH2), 7.46 (2H, d, J 8.6 Hz), 7.54 (2H, d, J 8.6 Hz), 7.69 (1H, s); MS (EI) m/e 228 (M+, 20), 193 (M+-35, 40), 149 (M+-79, 40), 115 (M+-113, 40), 43 (M+-185, 100); [HRMS (EI) m/z 228.0110 (M+). C11H10Cl2O requires M, 228.0109].
Preparation of 3-(chloromethyl)-4-(3'-fluorophenyl)-3-buten-2-one (3e).
This compound was prepared in the same manner as that described above: 87 mg (82%); a colorless solid; mp 63-64 oC; IR (KBr) ν 1640 cm-1 (C=O); 1H-NMR (CDCl3, 300 MHz) δ 2.51 (3H, s, Me), 4.42 (2H, s, CH2), 7.10-7.50 (4H, m, Ar), 7.69 (1H, s); MS (EI) m/e 212 (M+, 15), 177 (M+-35, 40), 99 (M+-113, 40), 43 (M+-169, 100); [HRMS (EI) m/z 212.0411 (M+). C11H10ClFO requires M, 212.0404].
Preparation of 3-(chloromethyl)-4-(4'-ethylphenyl)-3-buten-2-one (3f).
This compound was prepared in the same manner as that described above: 67 mg (60%); a colorless oil; IR (KBr) ν 1640 cm-1 (C=O); 1H-NMR (CDCl3, 300 MHz) δ 1.28 (3H, t, J 7.1 Hz), 2.51 (3H, s, Me), 2.67 (2H, q, J 7.1 Hz), 4.48 (2H, s, CH2), 7.31 (2H, d, J 8.0 Hz), 7.55 (2H, d, J 8.0 Hz), 7.69 (1H, s); MS (EI) m/e 222 (M+, 30), 193 (M+-29, 100), 128 (M+-94, 40); [HRMS (EI) m/z 222.0809 (M+). C13H15ClO requires M, 222.0811].
Preparation of 3-(chloromethyl)-4-phenyl-3-buten-2-one (3g).
This compound was prepared in the same manner as that described above: 75 mg (77%); a colorless oil; IR (KBr) ν 1640 cm-1 (C=O); 1H-NMR (CDCl3, 300 MHz) δ 2.52 (3H, s, Me), 4.46 (2H, s, CH2), 7.31-7.50 (3H, m, Ar), 7.51-7.61 (2H, m, Ar), 7.71 (1H, s); MS (EI) m/e 194 (M+, 100), 115 (M+-79, 40), 43 (M+-151, 40); [HRMS (EI) m/z 194.0498 (M+). C11H11ClO requires M, 194.0492].
Preparation of 3-(chloromethyl)-4-nonyl-3-buten-2-one (3h).
This compound was prepared in the same manner as that described above: 62 mg (50%); a colorless oil; IR (KBr) ν 1640 cm-1 (C=O); 1H-NMR (CDCl3, 300 MHz) δ 0.83 (3H, t, J 7.1 Hz, Me), 1.10-1.40 (12H, m, CH2), 1.40-1.60 (2H, m, CH2), 2.36 (3H, s, Me), 2.34 (2H, td, J 7.6, 7.6 Hz), 4.32 (2H, s, CH2), 6.85 (1H, t, J 7.6 Hz); MS (EI) m/e 244 (M+, 20), 209 (M+-35, 40), 109 (M+-135, 70), 43 (M+-201, 100); [HRMS (EI) m/z 244.1596 (M+). C14H25ClO requires M, 244.1594].