JPH0680662A - Alkoxymethylthiomethylsilane and production of thiolane compound using the same compound - Google Patents

Abstract

PURPOSE:To provide the subject new compound useful as an intermediate for production of a thiolane. CONSTITUTION:A compound of the formula (R<1> and R<2> are each H, a lower alkyl or phenyl; R<3> is a lower alkoxyalkyl, a lower alkyl or trimethylsilyl), e.g. methoxymethylthiomethyltrimethylsilane. The compound of the formula can be obtained by reacting alpha-trimethylsilylmethanethiol with n-butyllithium and then reacting chloromethyl methyl ether therewith.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a common intermediate for the production of thiolanes and their oxa analogs, 1,3-oxathiolanes, and thiolanes and 1,3-oxanes using the same.
The present invention relates to a method for producing oxathiolanes.

[0002]

2. Description of the Related Art Conventional methods for synthesizing thiolanes are
Method for obtaining 3-hydroxythiolane having a substituent at the 2-position from (2-haloethyl) oxiranes and hydrogen sulfide (Can. J. Chem. 56, 71 (1978)), halomethylthiomethylsilanes and carbonyl compounds A method of reacting with and in the presence of a fluorine ion to obtain 1,3-oxathiolane having a substituent at the 5-position (J. Chem. Soc., Ch
em.Commun., 1442 (1987)) or a method of reacting a mercaptoethanol derivative with a carbonyl compound to obtain 1,3-oxathiolane. However, these methods can only introduce a substituent into a limited position of the thiolane ring or the 1,3-oxathiolane ring.

[0003]

DISCLOSURE OF THE INVENTION An object of the present invention is to provide a method for producing thiolanes and 1,3-oxathiolanes having a substituent at an arbitrary position, and a common production intermediate which can be used for their production. Especially.

[0004]

The present invention is represented by the general formula 1 (In the formula, R ¹ and R ² represent hydrogen, a lower alkyl group or a phenyl group, and R ³ represents a lower alkoxyalkyl group, a lower alkyl group or a trimethylsilyl group.)

Alkoxymethylthiomethylsilane represented by and a general formula using the same (In the formula, R ¹ , R ² , R ⁵ , R ⁶ and R ⁷ represent hydrogen, a lower alkyl group or a phenyl group.)

The thiolanes represented by and the general formula (In the formula, R ¹ and R ² are the same as those described above, and R ^1
4 represents a lower alkyl group, a lower aralkyl group, a lower cycloalkyl group or a phenyl group, a lower alkyl group, a phenyl group which may be substituted with a halogen or a lower alkoxy group. The present invention provides a novel method for producing 1,3-oxathiolanes represented by the formula (1).

The present invention will be described in detail below. As a method for obtaining the novel alkoxymethylthiomethylsilane represented by the general formula (Formula 1) of the present invention, α-trimethylsilylmethanethiol is reacted with n-butyllithium, and then chloromethyl represented by chloromethyl methyl ether. Method of reacting ethers, substituted methanethiol is reacted with n-butyllithium in the same manner as, and then reacted with chloromethyl ethers, and the obtained acetal compound is equivalent to tetramethylethylenediamine (hereinafter abbreviated as TMEDA). ) Is again treated with n-butyllithium, followed by silylation by reaction with chlorotrimethylsilane to obtain alkoxymethylthiomethylsilane, or substituted methanethiol in the presence of an equivalent amount of TMEDA. An equivalent amount of n-butyllithium is reacted to produce dianio And then, it was silylated using chlorotrimethylsilane and the resulting trimethylsilyl body of a catalytic amount 18-Crown-6
There is a method of reacting with an aldehyde in the presence of ether and potassium cyanide to obtain an O-trimethylsilyl acetal compound.

The alkoxymethylthiomethylsilane represented by the general formula (Formula 1) obtained by the above method is represented by the general formula 2 R ⁴ --CHO (wherein R ⁴ is a lower alkyl group or a lower group) in the presence of a fluorine ion. Represents an aralkyl group, a lower cycloalkyl group, a phenyl group, a lower alkyl group, a halogen, or a phenyl group which may be substituted with a lower alkoxy group.)

Reaction with an aldehyde represented by the formula: (Wherein R ¹ and R ² represent hydrogen, a lower alkyl group or a phenyl group, R ³ represents a lower alkoxyalkyl group, a lower alkyl group or a trimethylsilyl group, and R
⁴ represents a lower alkyl group, a lower aralkyl group, a lower cycloalkyl group, or a phenyl group, a lower alkyl group, a phenyl group which may be substituted with a halogen or a lower alkoxy group. The alcohol compound represented by the formula (1) is obtained, and then the ring is closed using an acid catalyst to produce the 1,3-oxathiolane represented by the general formula (Formula 4).

Aldehydes used in this step include acetaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde, valeraldehyde, lower alkyl aldehydes such as 2,2-dimethylpropanal, and lower cycloalkanecarbaldehyde such as cyclohexanecarbaldehyde. And lower aralkyl aldehydes such as phenethyl aldehyde and 2,2-dimethyl-3-phenylpropanal. Furthermore, haloaldehydes such as benzaldehyde, tolylaldehyde, anisaldehyde, fluorobenzaldehyde, chlorobenzaldehyde, etc., lower alkyl groups such as biphenylaldehyde, lower alkoxy groups, aromatic aldehydes optionally substituted with halogen atoms or phenyl groups. Can be given.

The amount of aldehyde used is usually 0.5 to 2.1 equivalents relative to the alkoxymethylthiomethylsilane (Chemical formula 1). As the fluorine ion, for example, a quaternary ammonium fluoride such as tetranormalbutylammonium fluoride or a fluoride of a Group 1 element of the periodic table such as cesium fluoride and lithium fluoride is used. The amount used is usually relative to alkoxymethylthiomethylsilane
The amount is 0.1 to 0.6 equivalent, preferably 0.2 to 0.4 equivalent. This reaction can usually be carried out in a solvent such as tetrahydrofuran or acetonitrile. The amount used is usually 1-fold amount to a large excess amount of the reaction substrate. The reaction temperature is usually from room temperature to the boiling point of the solvent.

The alcohol compound (Chemical Formula 3) thus obtained can be subjected to usual post-treatment or, if necessary, further purified by silica gel column chromatography and taken out, and treated with an acid catalyst in the next step. According to this, the 1,3-oxathiolane compound of the above-mentioned formula (Formula 4), which is the target, can be produced. Examples of the acid catalyst used in the reaction include sulfuric acid or hydrochloric acid.
The amount used is a catalytic amount. The reaction is performed at 0 ° C to room temperature. This reaction is usually performed in a halogenated hydrocarbon solvent such as methylene chloride, and the amount thereof is usually 1 with respect to the reaction substrate.
Double to large excess. The compound thus obtained (Chemical Formula 4) can be subjected to a usual post-treatment or, if necessary, further purified by silica gel column chromatography and taken out.

In the present invention, the alkoxymethylthiomethylsilane represented by the general formula (Formula 1) is represented by the general formula (In the formula, R ⁵ , R ⁶ and R ⁷ represent hydrogen, a lower alkyl group or a phenyl group)

A silyl enol ether represented by the following formula is reacted in the presence of a Lewis acid to give a compound of formula 6 (In the formula, R ¹ , R ² , R ⁵ , R ⁶ and R ⁷ represent hydrogen, a lower alkyl group or a phenyl group.), Which is then subjected to ring closure in the presence of a fluorine ion. A thiolane represented by the above general formula (Formula 7) can be produced by reacting.

As the silyl enol ethers of Chemical formula 5 used in this reaction, 2,2-dimethylvinyltrimethylsilyl enol ether and (Z) -1-phenyl-2-
Methyl vinyl trimethyl silyl enol ether etc. can be mentioned. The amount used is usually 1 to 2 equivalents relative to the alkoxymethylthiomethylsilane represented by (Chemical Formula 1).

As the Lewis acid for the catalyst, a mixture of trivalent indium chloride and chlorotrimethylsilane is used, and its composition is 2.5 to 5 equivalents of chlorotrimethylsilane to 1 equivalent of trivalent indium chloride. The range up to can be used. The Lewis acid comprising these mixtures may be used in a catalytic amount. The reaction is usually performed in a halogenated hydrocarbon solvent such as methylene chloride. Reaction temperature is 0 ° C
~ Up to room temperature. After completion of the reaction, the carbonyl compound (Chemical Formula 6) can be obtained by subjecting the reaction mass to usual post-treatments such as diluting with water, neutralization and washing, separating and concentrating, or further purifying by silica gel column chromatography or the like if necessary. Obtainable.

The carbonyl compound (Chemical Formula 6) thus obtained can be further treated with a fluorine ion to be converted into a thiolane compound (Chemical Formula 7). Examples of the fluorine ion source used at that time include a quaternary ammonium fluoride salt such as tetranormalbutylammonium fluoride or a fluoride of a Group 1 element of the periodic table such as cesium fluoride and lithium fluoride. The amount thereof used is usually 0.1 to 1.0 equivalent based on the intermediate carbonyl compound (Chemical Formula 6).

This reaction can usually be carried out in a solvent such as tetrahydrofuran or acetonitrile. The amount used is usually 1-fold amount to a large excess amount of the reaction substrate. The reaction temperature is usually from room temperature to the boiling point of the solvent. The thiolanes thus obtained can be taken out by the same post-treatment method as that for the carbonyl compound.

[0019]

INDUSTRIAL APPLICABILITY According to the present invention, thiolanes having an arbitrary substitution pattern and its oxa analog 1,3-oxathiolanes can be efficiently obtained from a common intermediate.

[0020]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to the following examples.

Example 1 A two-necked flask containing a molecular sieve 4A and a magnetic rotor and replaced with argon was heated and dried under reduced pressure. In this, 5 ml of tetrahydrofuran and a tetrahydrofuran solution of tetra-n-butylammonium fluoride (0.8
M) 0.125 ml (0.1 mmol) was added. 2.
After stirring for 5 hours, 53 mg of benzaldehyde (0.5 m
mol) and methoxymethyltrimethylsilylmethyl sulfide (150 mg, 0.91 mmol) were added at room temperature for 2
Stir for 2 hours. The reaction mass was diluted with ether and washed with water. After liquid separation, the organic layer is dried with Glauber's salt and the desiccant is filtered off.
The solvent was distilled off from the filtrate. The resulting oil was separated and purified by silica gel thin layer chromatography to obtain methoxymethyl β
-Hydroxyphenethyl sulfide was obtained with a yield of 84%.

Analytical value of methoxymethyl β-hydroxyphenethyl sulfide. ¹ HNMR (60 MHz, TMS / CCl ₄ ) δ: 2.62 (dd, J = 7.8, 13.8 Hz, 1
H), 2.82 (dd, J = 4.2, 13.8 Hz, 1
H), 3.02 (s, br. 1H,), 3.28 (s,
3H), 4.44 (d, J = 12.0Hz, 1H),
4.55 (d, J = 12.0 Hz, 1H), 4.61
(Dd, J = 4.2, 7.8 Hz, 1H), 7.15
(S, 5H). IR. (Neat film): 3440, 2940, 1450,
1350, 1180, 1080, 940, 900, 73
0,700 cm ^-1 .

Examples 2 to 6 As in Example 1, except that p-anisaldehyde, p-biphenylaldehyde, p-chlorobenzaldehyde, 2,2-dimethylpropanal or cyclohexanecarbaldehyde was used instead of benzaldehyde, respectively. The reaction was performed to obtain the alcohol compounds of Examples 2 to 6.

Example 7 An appropriate amount of molecular sieve 4A was put in a flask, and the inside of a two-necked flask purged with nitrogen was heated and dried under reduced pressure. 5mL of THF and TBAF / THF solution (0.71M)
0.57 ml (0.40 mmol) was charged and the mixture was stirred for 2 hours. 324 mg (2.00 mmol) of 2,2-dimethyl-3-phenylpropanal and 164 mg (1.00 mmo) of methoxymethylthiomethyltrimethylsilane.
1) was added to this and the mixture was stirred at room temperature for 24 hours. Furthermore, TBAF / THF solution (0.90M) 0.23 ml
(0.21 mmol) was added and the mixture was stirred for a total of 67 hours. After completion of the reaction, the reaction mass was filtered through Celite and hydrolyzed with water. The organic layer extracted with ether was dried, the desiccant was filtered off, and the filtrate was concentrated. The concentrate was purified by silica gel column chromatography and ethyl acetate / hexane = 1
Yield of 3,3-dimethyl-4-phenyl-1-methoxymethylthiobutan-2-ol with Rf value 0.41 in a developing solvent of / 5
Obtained at 59%.

Analysis value of 3,3-dimethyl-4-phenyl-1-methoxymethylthiobutan-2-ol ¹ HNMR (60 MHz, TMS / CDCl ₃ ) δ: 0.83 (s, 3H), 0.93 ( s, 3H),
2.50 (dd, J = 9.0, 14.0 Hz, 1H),
2.53 (d, J = 13.0 Hz, 1H), 2.77
(D, J = 13.0 Hz, 1H), 2.93 (dd, J
= 2.0, 14.0 Hz, 1H), 3.27-3.53
(M, 1H), 3.30 (dd, J = 2.0, 9.0H
z, 1H), 3.35 (s, 3H), 4.47 (d, J
= 12.0 Hz, 1H), 4.63 (d, J = 12.0)
Hz, 1H), 7.15 (s, 5H). EI mass spectrum m / e (% relative intensity): 2
22 (M ⁺ -MeOH; 3.8), 195 (1.7),
162 (11.2), 145 (6.9), 133 (9.
0), 121 (8.0), 91 (100), 89 (2)
4.3), 69 (50.7), 65 (15.4), 60
(30.2), 45 (97.8) IR (neat film): 3450, 2940, 2340,
1490, 1470, 1450, 1180, 1080,
700,665 cm ^-1 .

3,3-Dimethyl-4-phenyl-1-methoxymethylthiobutane-2 obtained by such a method
5 ml of a methylene chloride solution containing all-134 mg (0.52 mmol) was prepared. 5 drops of concentrated sulfuric acid was added thereto, and the mixture was stirred at room temperature for 40 minutes. After completion of the reaction, the reaction solution was added to saturated aqueous sodium hydrogen carbonate to make it alkaline. After separation, the aqueous layer was extracted twice with methylene chloride and twice with ether, and the extract was added to the organic layer. The organic layer dried over anhydrous magnesium sulfate was filtered, and the solvent was distilled off from the filtrate. The resulting concentrate was subjected to silica gel column chromatography using an elution solvent containing a small amount of trimethylamine to give 5- (β-
Dimethylphenethyl) -1,3-oxathiolane was obtained.

Analysis value of 5- (β-dimethylphenethyl) -1,3-oxathiolane ¹ HNMR (60 MHz, TMS / CDCl ₃ ) δ: 0.87 (s, 3H), 0.97 (s, 3H),
2.33-2.97 (m, 4H), 3.45 (dd, J
= 6.0, 9.0 Hz, 1H), 4.67 (d, J =
5.4 Hz, 1 H), 4.93 (d, J = 5.4 Hz,
1H), 7.12 (s, 5H). EI mass spectrum m / e (% relative intensity): 2
22 (M ⁺ ; 21.2), 145 (5.3), 130
(31.8), 101 (25.2), 91 (100),
55 (27.6), 43 (33.4). IR (neat film): 2975, 2860, 2375,
1600, 1495, 1460, 1390, 1365,
1295, 1220, 1115, 1070, 1030,
700,665 cm ^-1 .

Examples 8 and 9 P-anisaldehyde was used in place of 2,2-dimethyl-3-phenylpropanal used in Example 7, and methoxyethoxymethylthiomethyltrimethylsilane was used in place of methoxymethylthiomethyltrimethylsilane. And phenyl (methoxymethylthio) methyltrimethylsilane, respectively, to obtain alcohol compounds of Examples 8 and 9 shown in (Table 1).

[0029]

[Table 1] Reaction of alkoxymethylthiomethylsilane (Chemical Formula 1) with aldehyde ────────────────────────────────── --Chemical 1 Aldehyde TBAF reaction 3 Example R ¹ R ² R ³ R ⁴ CHO Equivalent time Yield 1 H H Me Ph 0.2 + 0.2 48hr 84% 2 H H Me p-MeOC6H4 0.2 48hr 72% 3 H H Me p -PhC6H4 0.2 + 0.2 48hr 63% 4 H H Me p-ClC6H4 0.2 + 0.2 72hr 44% 5 H H Me Me3C 0.2 47hr 87% 6 H H Me C6H11 0.4 67hr 64% 7 H H Me PhCH2 (Me) 2C 0.4+ 0.2 67hr 59% 8 H H MeOCH ₂ CH ₂ p-MeOC6H4 0.2 + 0.2 46hr 60% 9 Ph H Me p-MeOC6H4 0.2 22hr 82% ─────────────────── ─────────────── 1) The molar ratio is based on (Chemical formula 1) /aldehyde/TBAF=1/2/0.2. 2) Tetrahydrofuran was used as the reaction solvent. 3) The reaction temperature was room temperature. 4) TBAF (tetranormal butyl ammonium fluoride) was added as needed. Additional equivalents are indicated by numbers with a + sign. 5) All yields are purification yields after column chromatography.

In the same manner as in Example 7, the alcohol compound of formula (Formula 3) in Table 1 is cyclized using an acid catalyst to obtain 1,3-oxathiolane of formula (Formula 4) shown in (Table 2).

[0031]

[Table 2]

Example 10 A flask in which 221 mg (1.00 mmol) of InCl _{3 was} weighed was replaced with nitrogen and then heated under reduced pressure to obtain In.
The Cl ₃ was dried. 30 ml of methylene chloride and 0.63 ml of chlorotrimethylsilane (d = 0.858) (5
40 mg, 4.98 mmol) was added and the mixture was stirred at room temperature for 4 minutes. 2.40 g (10.00 mmol) of phenyl (methoxymethylthio) methyltrimethylsilane and 2.88 g (2 of 1-trimethylsiloxy-2-methylpropene
(0.00 mmol) methylene chloride solution (20 ml) was added at 0 ° C., the mixture was stirred at the same temperature for 3.5 hours, and further stirred at room temperature for 1 hour.
Stir for hours. The reaction mass is filtered and hydrolyzed with water,
The separated organic layer and ether extraction layer were combined, dried, filtered, and the filtrate was concentrated. The concentrate was purified by silica gel column chromatography to give a yield of 2.58 g (9.20 mmo).
l) 3- [phenyl (trimethylsilyl) with a yield of 92%
Methylthio] -2,2-dimethylpropanal was obtained.

Analysis value of 3- [phenyl (trimethylsilyl) methylthio] -2,2-dimethylpropanal ¹ HNMR (60 MHz, TMS / CCl ₄ ) δ: 0.12 (s, 9H), 1.12 (s, 3H),
1.15 (s, 3H) 2.42 (d, J = 13.0H
z, 1H), 2.58 (d, J = 13.0Hz, 1
H), 3.22 (s, 1H), 7.23 (s, 5H),
9.38 (s, 1H). EI mass spectrum m / e (% relative intensity): 26
5 (0.6), 224 (3.0), 195 (41.
0), 135 (21.8), 91 (13.1), 73
(100), 45 (36.2). IR (neat film): 2950, 1725, 1690,
1490, 1465, 1445, 1250, 1070,
850,700 cm ^-1 .

An appropriate amount of molecular sieve 4A was charged, and the atmosphere was replaced with nitrogen, and THF was placed in a two-necked flask which was heated and dried under reduced pressure.
5 ml, TBAF / THF solution (0.68M) 0.29
mL (0.20 mmol) and previously purified 3- [phenyl (trimethylsilyl) methylthio] -2,2-dimethylpropanal 140 mg (0.50 mmol) were added, and the mixture was stirred at room temperature for 23 hours. After completion of the reaction, the reaction mass was filtered through Celite and hydrolyzed with water. The aqueous layer was extracted with ether, the organic layer separated was dried together, the desiccant was filtered off, and the filtrate was concentrated. The obtained concentrate was purified by silica gel column chromatography to obtain the target diastereomer mixture in a total yield of 92%.

Analysis value of diastereomer having Rf value of 0.40 in developing solvent of ethyl acetate / hexane = 1/5. ¹ HNMR (270 MHz, TMS / CDCl ₃ ) δ: 1.14 (s, 6H), 1. 80 (s, 1H),
2.62 (d, J = 10.6 Hz, 1H), 2.98
(D, J = 10.6 Hz, 1H), 3.63 (d, J =
9.2 Hz, 1 H), 4.10 (d, J = 9.2 Hz,
1H), 7.22-7.35 (m, 3H), 7.43-
7.55 (m, 2H). ¹³ CNMR (270 MHz, TMS / CDCl ₃ ) δ: 20.0, 26.2, 40.3, 43.6, 54.
2, 87.3, 127.7, 128.4 (2C), 12
8.6 (2C), 140.2.

Analysis value of diastereomer having Rf value 0.49 ¹ HNMR (270 MHz, TMS / CDCl ₃ ) δ: 1.22 (s, 6H), 1.52 (s, 1H),
2.60 (d, J = 9.9Hz, 1H), 3.20
(D, J = 9.9 Hz, 1H), 3.68 (d, J =
3.3 Hz, 1 H), 4.84 (d, J = 3.3 Hz,
1H), 7.28-7.39 (m, 3H), 7.51-
7.54 (m, 2H). ¹³ CNMR (270 MHz, TMS / CDCl ₃ ) δ: 22.6, 25.3, 42.9, 48.1, 56.
6, 83.8, 127.8, 128.6 (2C), 12
9.3 (2C), 136.9.

Example 11 The reaction was carried out under the same conditions as in Example 10 except that α-trimethylsilylbenzyl α′-trimethylsilyloxybenzyl sulfide of Reference Example 4 was used instead of phenyl (methoxymethylthio) methyltrimethylsilane.
-[Phenyl (trimethylsilyl) methylthio] -3-
Phenyl-2,2-dimethylpropanal was obtained, and the following reaction was carried out using this as a raw material.

Molecular sieve 4A in a 2-neck flask
Was put in an appropriate amount and replaced with nitrogen. While heating under reduced pressure to dry the inside of the flask, 5 ml of THF, 0.18 ml (0.18 mmol) of TBAF / THF solution (1.0 M) and 3- [phenyl (trimethylsilyl) methylthio] -3 obtained by the above method. -Phenyl-2,2-dimethylpropanal (125 mg, 0.35 mmol) was added to the mixture at room temperature for 23 hours.
Stir for hours. After the reaction was completed, it was filtered through Celite and hydrolyzed with water. The organic layer extracted with ether was dried, the desiccant was filtered off, and the filtrate was concentrated. The obtained concentrate was purified by silica gel column chromatography and combined with a developing solvent of hexane / ethyl acetate = 8/1 to obtain 83% of the target diastereomer having an Rf value of 0.20 and an Rf value of 0.67.
It was obtained in a yield of.

Analysis value of diastereomeric compound having Rf value of 0.20 ¹ HNMR (270 MHz, TMS / CDCl ₃ ) δ: 0.84 (s, 3H), 1.05 (s, 3H),
1.86 (s, 1H), 3.82 (d, J = 9.56H
z, 1H), 4.29 (d, J = 9.56Hz, 1
H), 4.52 (s, 1H), 7.20-7.55.
(M, 10H). ¹³ CNMR (270 MHz, TMS / CDCl ₃ ) δ: 14.2, 24.7, 47.4, 53.8, 57.
3,88.3,127.6,127.7,127.8
(2C), 128.5 (2C), 128.6 (2C),
129.5 (2C), 136.8, 140.3.

Examples 12 and 13 Except that phenyl (methoxymethylthio) methyltrimethylsilane was replaced by methoxymethylthiomethyltrimethylsilane or α-trimethylsilylmethyl α'-trimethylsilyloxypropyl sulfide produced in Reference Example 3 in Example 10. The same reaction was performed to obtain the thiolane compound of Example 12 or Example 13, respectively.

Example 14 Using the phenyl (methoxymethylthio) methyltrimethylsilane obtained in Reference Example 2 and 1-phenyl-2-trimethylsilyloxypropene, a reaction was conducted under the same conditions as in Example 10 A thiolane compound was obtained.

[0042]

[Table 3] TBAF: represents tetra-n-butylammonium fluoride. The reaction time represents the reaction time from (Chemical formula 6) to (Chemical formula 7).

Next, Reference Examples 1 to 4 show methods for producing alkoxymethylthiomethylsilanes (Chemical Formula 1) which are the compounds of the present invention.

Reference Example 1 Synthesis of methoxymethylthiomethyltrimethylsilane A magnetic rotor was placed in a two-necked flask, heated under reduced pressure, and replaced with argon. 40 ml of ether and 3.58 g (30 mmol) of trimethylsilylmethanethiol were charged therein, and after cooling to −78 ° C., 19.5 ml (1.62 M, 32 mmol) of a hexane solution of butyl lithium was slowly added. After the addition was completed, the temperature was raised to room temperature.
The mixture was stirred for 5 hours. After cooling to 0 ° C., 2.18 ml (29 mmo) of chloromethyl methyl ether (d = 1.07)
l) was added. After stirring at room temperature for 2 hours, it was hydrolyzed with a saturated aqueous sodium hydrogen carbonate solution. After liquid separation, the aqueous layer was extracted with ether three times, and the obtained organic layer was dried with sodium sulfate. After filtering the desiccant, the filtrate was concentrated. CaH ₂ was added to the obtained oil as a desiccant and distilled. Boiling point 88-90 ° C
4.02 g of (48 mmHg) methoxymethylthiomethyltrimethylsilane was obtained with a yield of 82%.

Analysis value of methoxymethylthiomethyltrimethylsilane ¹ HNMR (60 MHz, TMS / CDCl ₃ ) δ: 0.10 (s.9H), 1.83 (s, 2H),
3.30 (s, 3H), 4.52 (s, 2H).

Reference Example 2 Synthesis of Phenyl (methoxymethylthio) methyltrimethylsilane 30 ml of ether and benzyl mercaptan (d = 1.058) were placed in a 100 ml two-necked flask equipped with a septum cap and charged with a magnetic rotor and purged with nitrogen. 52 ml
(3.72 g, 30 mmol) was added. After the reaction solution was cooled to -78 ° C, butyllithium hexane solution 19.4
ml (1.6 M, 31 mmol) was added slowly.
After the addition was completed, the mixture was stirred for 1 hour at the same temperature, then warmed to room temperature and stirred for 2 hours. The reaction solution was cooled to 0 ° C. and chloromethyl methyl ether (d = 1.07) 2.33 ml
(2.50 g, 31 mmol) was added, the mixture was reacted at 0 ° C. for 1 hour, then warmed to room temperature, and reacted overnight. The reaction mass was poured into a saturated aqueous solution of sodium hydrogen carbonate and the layers were separated. The aqueous layer was extracted 3 times with ether, and the organic layer was dried with sodium sulfate. After filtering the drying agent, the filtrate was concentrated. CaH ₂ was added to the concentrate and distilled to quantitatively obtain methoxymethylbenzyl sulfide having a boiling point of 88 ° C./2.5 mmHg.

Analysis value of methoxymethylbenzyl sulfide ¹ HNMR (60 MHz, TMS / CDCl ₃ ) δ: 3.33 (s.3H), 3.73 (s, 2H),
4.48 (s, 2H) 7.28 (s, 5H).

4.76 g (30 mmol) of methoxymethylbenzyl sulfide thus obtained, 125 ml of hexane and 4.82 ml (32 mmo) of TMEDA (tetramethylethylenediamine) (d = 0.77).
l) was placed in a two-necked flask equipped with a septum cap, which was charged with a magnetic rotor and purged with nitrogen. After cooling this to -10 ° C, 20.6 ml of butyllithium hexane solution (1.
6M, 33 mmol) was added slowly. After the addition was completed, the mixture was stirred for 3 hours at the same temperature. 20 ml of hexane and chlorotrimethylsilane (d = 0.
858) 4.4 ml (35 mmol) was added. -10
The solution was cooled to 0 ° C. and the solution prepared above was added dropwise thereto. −
After reacting overnight at 10 ° C., the mixture was poured into water, extracted with ether, and dried with sodium sulfate. The desiccant is filtered off, the filtrate is concentrated and calcium hydride is added to the oil obtained and distilled to give a boiling point of 1
The yield of phenyl (methoxymethylthio) methyltrimethylsilane at 20 ° C./0.08 mmHg was 5.81 g, (2
5 mmol) was obtained with a yield of 83%.

Analysis value of phenyl (methoxymethylthio) methyltrimethylsilane ¹ HNMR (60 MHz, CH ₂ Cl ₂ / CCl ₄ ) δ: 0.15 (s.9H), 3.32 (s, 3H),
3.45 (s, 1H), 4.28 (d, J = 11 Hz,
1H), 4.58 (d, J = 11 Hz, 1H), 7.3
0 (s, 5H).

Reference Example 3 Synthesis of trimethylsilylmethyl α-trimethylsilyloxypropyl sulfide 5.76 Trimethylsilylmethylthiotrimethylsilane
g (30 mmol) and propionaldehyde (d = 0.
804) 2.0 ml (1.6 g, 28 mmol) was charged into a flask whose atmosphere was replaced with nitrogen. 12 mg (0.036 m) of a mixture of KCN and 18-crown-6 under a nitrogen stream.
(mol) was added to this and stirred. During this, the reaction mass was cooled with ice water and stirred for 5.5 hours. This was distilled under reduced pressure to collect a fraction having a boiling point of 65 to 67 ° C./1 mmHg. Trimethylsilylmethyl α − with a yield of 5.19 g and a yield of 74%
Trimethylsilyloxypropyl sulfide was obtained.

Analysis value of trimethylsilylmethyl α-trimethylsilyloxypropyl sulfide ¹ HNMR (60 MHz, CHCl ₃ / CCl ₄ ) δ: 0.13 (s.9H), 0.16 (s, 9H),
0.94 (t, J = 7.0 Hz, 3H), 1.73
(S, 2H), 1.50-2.06 (m, 2H), 4.
58 (t, J = 6.0 Hz, 1H). EI mass spectrum m / e (% relative intensity) 250 (0.
4), 192 (3.2), 177 (4.6), 131 (58.4), 115 (3.6), 73 (100), 59
(7.8).

Reference Example 4 Synthesis of α-trimethylsilylbenzyl α′-trimethylsilyloxybenzyl sulfide Phenyl (trimethylsilylthio) methyl trimethylsilane 2.58 g (9.6 mmol) and benzaldehyde (d = 1.05) 0.88 ml (924 mg, 8.7 mmo
1) and were charged in a flask in which nitrogen was replaced. A catalytic amount of a mixture of KCN and 18-Crown-6 was added under a nitrogen stream, and the mixture was stirred at room temperature for 8 hours. This is distilled under reduced pressure to 136-1
The fraction of 41 ° C / 0.8mmHg was collected, and the yield was 2.35g.
(6.3 mmol) with a yield of 72%, α-trimethylsilylbenzyl α′-trimethylsilyloxybenzyl sulfide was obtained.

Claims (3)

[Claims] 1. A general formula 1 (Wherein R ¹ and R ² represent hydrogen, a lower alkyl group or a phenyl group, and R ³ represents a lower alkoxyalkyl group, a lower alkyl group or a trimethylsilyl group). 2. A general formula 1 (In the formula, R ¹ , R ² , and R ³ are the same as above.) The alkoxymethylthiomethylsilane represented by the general formula 2 R ⁴ —CHO (wherein R ⁴ is a lower alkyl group, a lower aralkyl group, A lower cycloalkyl group or a phenyl group, a lower alkyl group, a halogen, or a phenyl group which may be substituted with a lower alkoxy group.) In the presence of a fluorine ion. (In the formula, R ¹ and R ² represent hydrogen, a lower alkyl group or a phenyl group, R ³ represents a lower alkoxyalkyl group, a lower alkyl group or a trimethylsilyl group, and R ⁴
Represents a lower alkyl group, a lower aralkyl group, a lower cycloalkyl group, a phenyl group, a lower alkyl group, a halogen, or a phenyl group which may be substituted with a lower alkoxy group. ) To obtain an alcohol compound, which is then treated with an acid for ring closure.
Conversion 4 (In the formula, R ¹ , R ² and R ⁴ are the same as above.) A method for producing 1,3-oxathiolanes. 3. A general formula 1 (Wherein R ¹ and R ² represent hydrogen, a lower alkyl group or a phenyl group, and R ³ represents a lower alkoxyalkyl group, a lower alkyl group or a trimethylsilyl group).
Conversion 5 (In the formula, R ⁵ , R ⁶ and R ⁷ represent hydrogen, a lower alkyl group or a phenyl group.) The silyl enol ether represented by the general formula 6 (In the formula, R ¹ , R ² , R ⁵ , R ⁶ and R ⁷ represent hydrogen, a lower alkyl group or a phenyl group.), Which is then subjected to ring closure in the presence of a fluorine ion. General formula 7 characterized by reacting (In the formula, R ¹ , R ² , R ⁵ , R ⁶ and R ⁷ are the same as the above.) A method for producing a thiolane compound.