JPH0346477B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel 1,3-oxazolidine- or 1,3-thiazolidine-2-thione compounds, and more particularly to 1,3-oxazolidine- or 1,3-thiazolidine-2-thiones. This invention relates to a halogenated phosphorus derivative of a compound and a method for producing the same. It has already been reported that 1,3-thiazolidine-2-thione has an excellent function as an activator for the carboxyl group of carboxylic acid. for example,
Y.Nagao andE.FUJITA, Heterocycles, 17 ,
See 537 (1982). This document describes that 3-acyl-1,3-thione obtained by dehydrating and condensing carboxylic acid and 1,3-thiazolidine-2-thione with dicyclohexylcarbodiimide (DCC) in the presence of a basic catalyst such as pyridine. Thiazolidine-
2-thione is easily converted into alcohol when treated with sodium borohydride, converted into aldehyde when treated with diisobutylaluminum hydride, and selectively converted into aldehyde when treated with various amines, amino alcohols, aminothiols, etc. It has been described that the desired amides can be derived in high yields, and thus 1,3-thiazolidine-2-thione has been shown to be extremely useful as an activating reagent for carboxylic acids.
However, 1,3-thiazolidine-2-thione requires a condensing agent such as DCC when activating the carboxylic acid, and there are some problems when using this reagent industrially. Therefore, the present inventors conducted extensive research in search of a carboxylic acid activation reagent that does not require secondary reagents such as DCC, and found that 1,3-oxazolidine- Alternatively, the inventors discovered that halogenated phosphorus derivatives of 1,3-thiazolidin-2-one compounds are extremely suitable as activating reagents for carboxylic acids, leading to the completion of the present invention. Therefore, according to the present invention, the general formula In the formula, R ¹ represents a phenyl group or a phenoxy group; R ² and R ³ each independently represent a hydrogen atom, a lower alkyl group, or a lower alkoxycarbonyl group; R ⁴ and R ⁵ each independently represent a hydrogen atom or a phenyl group; represents a group; X represents a chlorine atom; Y and Z each independently represent an oxygen or sulfur atom; A compound represented by is provided. In this specification, the term "lower" refers to groups or compounds to which this term is attached, in which the number of carbon atoms is 6 or less;
This means that the number is preferably 4 or less. In the above formula (), the "lower alkyl group" may be linear or branched, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl,
tert-butyl, n-pentyl, isoamyl, n-
Examples include hexyl group. The lower alkyl moiety in the "lower alkoxycarbonyl group" has the above meaning, and specific examples of the lower alkoxycarbonyl group include methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, iso-propoxycarbonyl, etc. . Representative examples of the compound of the formula () are as follows. Phenylchlorothiophosphonic-N-(2-
thioxo-1,3-thiazolidide), phenylchlorothiophosphonic-N-(2-
thioxo-1,3-oxazolidide), phenylchlorophosphonic-N-(2-thioxo-1,3-thiazolidide), phenylchlorophosphonic-N-(2-thioxo-1,3-oxazolidide), Enylchlorophosphonic-N-(2-thioxo-4-ethyl-1,3-oxazolidide), Phenylchlorophosphonic-N-(2-thioxo-4-methyl-5-phenyl-1,3-oxazolidide) , phenylchlorophosphonic-N-(2-thioxo-4-methoxycarbonyl-1,3-oxazolidide), phenylchlorophosphonic-N-(2-thioxo-4,4-dimethyl-1,3-oxazolidide) ), phenylchlorophosphonic-N-(2-thioxo-4-methoxycarbonyl-1,3-thiazolidide), phenylchlorophosphonic-N-(2-thioxo-1,3-oxazolidide), phenylchloro Phosphoric-N-(2-thioxo-1,3-thiazolidide), Phenylchlorophosphoric-N-(2-thioxo-4-ethyl-1,3-oxazolidide), Phenylchlorophosphoric-N-( 2-thioxo-4-methyl-5-phenyl-1,3-oxazolidide), phenylchlorophosphonic-N-(2-thioxo-4-methoxycarbonyl-1,3-thiazolidide), phenylchlorophosphonic- N-(2-thioxo-4,4-dimethyl-1,3-oxazolidide), phenylchlorophosphonic-N-(2-thioxo-4-methyl-1,3-oxazolidide), phenylchlorophosphonic- N-(2-thioxo-4-isopropyl-1,3-oxazolidide), phenylchlorophosphonic-N-(2-thioxo-5-phenyl-1,3-oxazolidide), and the like. According to the invention, the compound of formula () is of the general formula In the formula, R ¹ , X and Y have the above meanings, and a compound of the general formula In the formula, R ² , R ³ , R ⁴ , R ⁵ and Z have the above-mentioned meanings, and can be produced by reacting the compound in the presence of a base. The reaction between the compound of formula () and the compound of formula () is generally carried out in an inert organic solvent, such as ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, dioxane, and diglyme; dimethylformamide, dimethylacetamide, hexamethylphosphoramide, etc. amides; hydrocarbons such as benzene, toluene, xylene, and cyclohexane; halogenated hydrocarbons such as dichloromethane and carbon tetrachloride; and dimethyl sulfoxide. The reaction temperature is not strictly limited and can be varied widely depending on the type of starting materials, etc., but generally the temperature is within the range of about -20°C to about 40°C, preferably about 0°C to room temperature. can be used. The amount of the compound of formula () to be used for the compound of formula () is not strictly limited and can vary widely depending on the type of compound of formula () and (), but generally, the amount of the compound of formula () used is not strictly limited. It is advantageous to use 1 to 5 mol, in particular 1 to 2 mol, of the compound of formula () per mol of compound. The above reaction can be carried out in the presence of a base,
Examples of bases that can be used include alkali metal hydrides such as sodium hydride and potassium hydride; alkali metal carbonates such as potassium carbonate and sodium carbonate;
Metal alkoxides such as potassium t-butoxide; amines such as diisopropylethylamine and triethylamine; these are represented by the formula ()
It can be used generally in a proportion of 1 to 10 mol, preferably 1 to 6 mol, per 1 mol of the compound. Under the conditions mentioned above, the reaction usually lasts for 10 minutes to 50 hours.
More generally, it can be completed in about 45 minutes to 25 hours. The resulting compound of formula () can be separated from the reaction mixture and purified by methods known per se, such as recrystallization, chromatography, extraction, distillation, etc. The phosphorus compound of the formula () used as a starting material in the above method is a known one, and the phosphorus compound of the formula ()
In, X is preferably a chlorine atom. In addition, at least a part of the compound of formula () is known, and even if it is new, it can be treated as a known compound, for example, by the following reaction formula. In the formula, R ² , R ³ , R ⁴ , R ⁵ and Z have the above meanings, and can be synthesized according to [For details, see for example Y, Nagao, etal; Chemical Abstract,
53, 2529g (1959) and Y. Nagao, etal;
See Tetrahedron Letters, 23 , 201 (1982)]. The compound of formula () provided by the present invention can be advantageously used as an activator for the carboxyl group of carboxylic acid in various chemical reactions involving carboxylic acid. Hereinafter, chemical reactions using the compound of formula () of the present invention will be explained in more detail. (1) Synthesis of azetidinone derivatives by intramolecular amidation (cyclization) of various β-amino acids: In the formula, R ¹⁰ , R ¹¹ , R ¹² , R ¹³ and R ¹⁴ are each independently a hydrogen atom or any substituent that does not directly participate in the reaction, such as alkyl, cycloalkyl, aryl, aralkyl, alkenyl, alkynyl, hetero ring, acylated amino is protected amino, protected carboxyl, alkoxy, alkylthio,
Represents a hydroxyl group, protected mercapto, carbamoyl, carbamoyloxy, or other group that may be optionally protected. The intramolecular amidation of the β-amino acid of the above formula (A) is
Usually suitable inert solvents such as ethers such as tetrahydrofuran and dioxane; chloroform,
In a halogenated hydrocarbon such as methylene chloride, 1,2-dichloroethane; acetonitrile, dimethylformamide, pyridine, ethyl acetate, etc. or a mixed solvent of at least one of these and water, preferably in the presence of a base, the formula ( This can be carried out by contacting the β-amino acid of A) with a compound of formula (). The temperature of this intramolecular amidation reaction is expressed by formula (A)
The temperature can be varied widely depending on the type of the β-amino acid and the compound of formula (), but generally a temperature between about room temperature and the reflux temperature of the reaction mixture can be used. It is convenient to use the compound of formula () in a proportion of generally 1 to 10 mol, preferably 1 to 5 mol, per 1 mol of β-amino acid of formula (A). In addition, the base is generally 1 mole of the β-amino acid of formula (A).
It can be used in a proportion of 1 to 10 mol, preferably 1 to 5 mol. Examples of bases that can be suitably used here include sodium carbonate, potassium carbonate, triethylamine, diisopropyl, ethylamine, pyridine, dimethylaminopyridine, quinoline, and 2,6-lutidine. The above intramolecular amidation is usually carried out for 10 minutes or more under the above conditions.
It can be completed in 50 hours, more commonly 0.5 to 30 hours. (2) Synthesis of active amide from carboxylic acid and synthesis of various carboxylic acid derivatives via the active amide: In the formula, R ¹⁵ represents a carboxylic acid residue, such as a linear, branched, or cyclic alkyl, alkenyl, or alkynyl group, aryl group, aralkyl group, or heterocyclic group; May be substituted with non-participating atoms or atomic groups, such as halogen atoms, cyano groups, nitro groups, protected hydroxyl groups, protected mercapto groups, alkoxycarbonyl groups; R ² , R ³ , R ⁴ , R ⁵ and Z have the meanings given above. The reaction between the carboxylic acid of formula (C) above and the compound of formula () is carried out under substantially the same conditions as described in the previous section (1) for the treatment of the β-amino acid of formula (A) with the compound of formula (). The active amide of formula (D) is obtained. This activated amide can be converted into various carboxylic acid derivatives by reduction or reaction with a Grignard reagent, amine, alcohol, thiol, etc., as shown in the reaction formula below. Each reaction shown in the above reaction formula can be carried out by a method known per se. For example, Y.
Nagao et al, J.Chem.Soc.Chem.Com., 330
(1978) and Y. Nagao et al, Tetrehedron
Letters, 21 , 841 (1981). In addition, the compound of formula () can be synthesized not only by intramolecular amidation of β-amino acid, but also by intramolecular amidation of other amino acids to synthesize a cyclic monoamide (see reaction formula below), or by amidation of dicarboxylic acid and diamine. It can also be advantageously used in the activation of the dicarboxylic acid in the synthesis of cyclic diamide (see reaction formula below). The synthesis reaction of these cyclic monoamides and cyclic diamides can be carried out by methods known per se. For example, Y. Nagao etal, Chemistry
Letters, 159 (1980). Furthermore, the compound of formula () of the present invention can be used as a reagent for activating the carboxyl group of an amino acid in peptide synthesis. Furthermore, when any one of R ² , R ³ , R ⁴ and R ⁵ represents a group as defined above other than a hydrogen atom, the compound of formula () has one or two asymmetric carbon atoms. and can exist as an optically active form. Such an optically active compound of formula () can be used to produce useful natural products such as prostaglandins, indole alkaloids, and calcomycin by asymmetric aldol condensation or asymmetric Diels-Alder reaction using the optically active compound as a chiral template. It is possible to use it for synthesis. An example of such asymmetric synthesis is shown in Reference Example 2 below. The present invention will be explained in more detail with reference to Examples below. Example 1: (+) Phenylchlorophosphonic
N-(2-thioxo-4-ethyl-1,3-
oxazolidide) (-)2-thioxo-4-ethyl-1,3-oxazolidine (1.31 g, 0.01 mol) and triethylamine (1.2 g, 0.012 mol) in dichloromethane (20 ml) was dissolved in phenylphosphonic acid dichloride (1.95 g, 0.01 mol). Dichloromethane (5ml)
The solution was added and stirred at room temperature for 24 hours. After evaporating the solvent under reduced pressure, the residue was purified by silica gel column chromatography (eluent: chloroform) to obtain a yellow oil (2.1 g): yield 73% [α] ²⁰ _D (c = 1.0, CHCl ₃ ): +110.3°NMR (CDCl ₃ , ppm): 1.00 (m, 3H), 2.05 (m,
2H), 4.56 (m, 3H), 7.56 (m, 3H), 8.00
(m, 2H) Elemental analysis value: C ₁₁ H ₁₃ ClNO ₂ PS Calculated value (%) 45.60 4.52 12.24 4.84 11.07 Actual value (%) 45.41 4.48 12.01 4.89 10.97 The following compounds were used in the above example The corresponding heterocyclic compound was synthesized by reacting it with phenylphosphonic acid dichloride according to a method similar to 1.
The name of the starting heterocyclic compound and the physical property values of the product are shown below. Phenylchlorophosphonic-N-(2-thioxo-1,3-thiazolidide) Yellow oil NMR from 2-thioxo-1,3-thiazolidine ( _CDCl3 , ppm): 3.50 (m, 2H), 4.70 (m,
2H), 7.30-8.20 (m, 5H) Elemental analysis value: C ₉ H ₉ ClNOPS ₂ , C H Cl N S Calculated value (%) 38.92 3.27 12.77 5.04 23.09 Actual value (%) 39.15 3.35 12.90 5.06 22.95 Phenyl Chlorophosphonic-N-(2-thioxo-1,3-oxazolidide) 2-thioxo-1,3-oxazolidine to yellow oil NMR ( _CDCl3 , ppm): 4.40 (m, 2H), 4.70 (m,
2H), 7.40-8.25 (m, 5H) Elemental analysis value: C ₉ H ₉ ClNO ₂ PS Calculated value (%) 41.31 3.47 13.55 5.35 12.25 Actual value (%) 41.09 3.48 13.60 5.31 12.18 Phenyl Chlorothiophosphonic-N-(2-
Thioxo-1,3-oxazolidide) From 2-thioxo-1,3-oxazolidine Melting point: 110-113°C NMR ( _CDCl3 , ppm): 4.30-4.70 (m, 4H),
7.40-8.20 (M, 5h) element analysis values: C ₉ h ₉ Clnops ₂ C H Clnops 2 C H CL N S calculation value (%) 38.92 3.27 12.77 5.09 Actual measurement value (%) 38.72 3.10 12.90 5.01 23.16 Fenylclorohos Honitsuku N-(2-thioxo-4,4-dimethyl-1,3-oxazolidide) Yield 70% from 2-thioxo-4,4-dimethyl-1,3-oxazolidine. Melting point: 143-146°C NMR ( _CDCl3 , ppm): 1.82 (d, 6H), 4.33 (8,
2H), 7.56 (m, 3H), 7.93 (m, 2H) Elemental analysis value: As C ₁₁ H ₁₃ ClNO ₂ PS, C H Cl N S Calculated value (%) 45.60 4.52 12.24 4.84 11.07 Actual value (%) 45.44 4.54 12.15 4.73 11.05 (+) Phenylchlorophosphonic-N-(2
-thioxo-4-methyl-5-phenyl-1,
3-oxazolidide) (+) From 4-thioxo-4-methyl-5-phenyl-1,3-oxazolidine. Yellow oil [α] ²⁰ _D (c=1.0, CHCl ₃ ): +110.3° NMR (CDCl ₃ , ppm): 1.13 (d, 3H), 5.06 (m,
1H), 5.96 (d, 1H), 7.53-8.00 (m, 10H) Elemental analysis value: C H Cl N S Calculated value (%) as C ₁₆ H ₁₅ ClNO ₂ PS 54.63 4.30 10.08 3.98 9.11 Actual value (%) 54.57 4.21 10.15 4.08 9.03 (-) Phenylchlorophosphonic-N-(2
-thioxo-4-methoxycarbonyl-1,3
-oxazolidide) 2-thioxo-4-methoxycarbonyl-1,
From 3-oxazolidine. Yellow oil [α] ^20D (c=1.23, _CHCl3 ): -41.7°NMR ( _CDCl3 , ppm): 3.90 (s, 3H), 4.30 _~
5.40 (m, 3H), 7.40 - 8.40 (m, 5H) Elemental analysis value: C ₁₁ H ₁₁ ClNO ₄ As PS C H Cl N S Calculated value (%) 41.33 3.47 11.09 4.38 10.03 Actual value (%) 41.28 3.45 11.32 4.57 10.15 (-)Phenylchlorophosphonic-N-(2
-thioxo-4-methoxycarbonyl-1,3
-thiazolidide) From (-)2-thioxo-4-methoxycarbonyl-1,3-thiozolidine. [α] ²⁰ _D (c=1.27, CHCl ₃ ): −90.0° NMR (CDCl ₃ , ppm): 4.00 (s, 3H), 4.90 (d,
2H), 5.45 (t, 1H), 7.40-8.70 (m, 5H) Elemental analysis value: C H Cl N S Calculated value (%) as C ₁₁ H ₁₁ ClNO ₃ PS ₂ 39.35 3.30 10.56 4.17 19.10 Actual value (% ) 39.28 3.19 10.51 4.11 19.01 Example 2: (+) Phenylchlorophosphoric
N-(2-thioxo-4-methyl-5-phenyl-1,3-oxazolidide To a solution of (+)2-thioxo-4-methyl-5-phenyl-1,3-oxazolidine (1.93 g, 0.01 mol) in dichloromethane (20 ml) was added triethylamine (1.2 g, 0.012 mol), followed by phenyl phosphate. A solution of dichloride (2.1 g, 0.01 mol) in dichloromethane (5 ml) was added and stirred at room temperature for 24 hours. The reaction mixture was worked up in the same manner as in Example 1 to give a yellow oil (3.0 g): Yield
82%. [α] ²⁰ _D (c=0.52, CHCl ₃ ): +39.9° NMR (CDCl ₃ , ppm): 1.10 (d, 3H), 4.90 (dq,
1H), 5.90 (d, 1H), 7.43 (m, 10H) Elemental analysis value: C ₁₆ H ₁₅ ClNO ₃ PS C H Cl N S Calculated value (%) 52.25 4.11 9.64 3.81 8.72 Actual value (%) 52.18 4.02 9.50 3.79 8.68 In the same manner as in Example 2 above, the following compounds were synthesized by reacting phenylphosphoric acid dichloride and the corresponding heterocyclic compound. The name of the starting heterocyclic compound and the physical properties of the product are shown below. Phenylchlorophosphoric-N-(2-thioxo-1,3-oxazolidide) From 2-thioxo-1,3-oxazolidine. Yellow oil NMR ( _CDCl3 , ppm: 4.10-4.80 (m, 4H), 7.40
(m, 5H) Elemental analysis value: C ₉ H ₉ ClNO ₃ PS C H Cl N S Calculated value (%) 39.93 3.27 12.77 5.04 11.55 Actual value (%) 39.20 3.21 12.59 5.16 11.48 (-) Phenylchlorophosphoric- N-(2
-thioxo-4-ethyl-1,3-oxazolidide) From (-)2-thioxo-4-ethyl-1,3-oxazolidine. [α] ²⁰ _D (c=3.1, CHCl ₃ ): −30.4° NMR (CDCl ₃ , ppm): 1.00 (t, 3H), 1.90 (dq,
2H), 4.30-4.80 (m, 3H), 7.35 (m, 5H) Elemental analysis value: As C ₁₁ H ₁₃ ClNO ₃ PS, C H Cl N S Calculated value (%) 43.22 4.29 11.60 4.58 10.49 Actual value (% ) 43.10 4.11 11.53 4.55 10.25 Phenylchlorophosphoric-N-(2-thioxo-1,3-thiazolidide) NMR of yellow oil from 2-thioxo-1,3-oxazolidide ( _CDCl3 , ppm): 3.50 (m, 2H), 4.63 (m,
2H), 7.36 (m, 5H) Elemental analysis value: C ₉ H ₉ ClNO ₂ PS ₂ Calculated value (%) 36.80 3.09 12.07 4.77 21.83 Actual value (%) 36.85 3.00 12.01 4.58 21.71 Reference example 1 : Synthesis of β-lactam-1 N-benzyl-2-azetidinone N-benzylaminopropionic acid (180 mg, 1
mmol) and phenylchlorophosphoric-N
Diisopropylethylamine (0.9 ml) was added to a solution of -(2-thioxo-4-ethyl-1,3-oxazolidide) (579 mg, 2 mmol) in acetonitrile (200 ml), and the mixture was refluxed for 1 hour. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel containing 3% silver nitrate (eluent: ethyl acetate) to obtain a colorless oil (115 mg): Yield 71
% NMR (CDCl ₃ , ppm): 2.95 (2H, t, J = (4),
3.15 (2H, t, J=4), 4.38 (2H, s),
7.31 (5H, m) -2 4-Phenyl-3-benzyl-2-azetidinone 3-phenyl-3-benzylaminopropionic acid (125 mg, 0.5 mmol) and phenylchlorophosphonic-N-(2-thioxo-4 -Methyl-
5-phenyl-1,3-oxazolidide) (352
(mg, 1 mmol) in acetonitrile (100 ml) was added diisopropylethylamine (0.45 ml) and refluxed for 1 hour. A slightly yellow oil (86 mg) was obtained by the same post-treatment as in Reference Example-1: Yield 72% NMR (CDCl ₃ , ppm): 2.88 (1H, brd, J = 15),
3.37 (1H, dd, J = 15.5), 3.78 (1H, d, J
= 15), 4.43 (1H, m), 4.78 (1H, d, J =
15), 7.3 (10H, m) Elemental analysis value: C ₁₆ H ₁₅ as NO C H N Calculated value (%) 80.98 6.37 5.90 Actual value (%) 81.13 6.24 5.87 -3 3-[(Z)-2-( 2-Tritylaminothiazol-4-yl)-2-methoxyiminoacetamide]-N-benzyl-2-azetidinone 2-[(Z)-2-(2-tritylaminothiazol-4-yl)-2- Methoxyiminoacetamide]
-3-Benzylaminopropionic acid (62 mg, 0.1
mmol) and phenylchlorophosphonic-N
-(2-thioxo-4,4-dimethyl-1,3-
Diisopropylethylethylamine (0.09 ml) was added to a solution of oxazolidine (58 mg, 0.2 mmol) in acetonitrile (20 ml) and refluxed for 4 hours.
Post-treatment was performed in the same manner as in Reference Example-1 to obtain the title compound (36.9 mg): yield 62% NMR (CDCl ₃ , ppm): 3.82 (5H, m), 4.40 (3H,
m), 6.80 (1H, s), 7.35 (20H, m) Reference example 2: Asymmetric aldol condensation 2-1 (+) 3-propionyl-4-ethyl-1,3-oxazolidine-2-thione Propionic acid ( 7.4 g, 0.1 mol), phenylchlorophosphonic-N-(2-thioxo-4-ethyl-1,3-oxazolidide) (29.0 g, 0.1 mol) and triethylamine (15 g) in dimethylformamide (150 ml). Stirred at room temperature for 24 hours. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: benzene) to obtain a slightly yellow oily product (12.9 g): yield 64% [α] ²⁰ _D (c = 1.0, CHCl ₃ ): +108°NMR (CDCl ₃ , ppm): 1.06 (m, 6H), 1.83 (m,
2H), 3.23 (m, 2H), 4.30 (m, 3H) 2-2 (-) Methyl 3-hydroxy-3-phenyl-2-methylpropionate of the product from 2-1 (384 mg, 2 mmol) A dichloromethane (4 ml) solution was cooled to 0°C, and with stirring trifluoromethanesulfonic acid 9-borabicyclo[3,3,1]nonane (0.6 g) and diisopropylethylamine (315 mg, 2.44 mmol) were added.
was added and stirred at 0°C for 30 minutes. Next, add the reaction solution to -78
Cool to 1.5 °C, add benzaldehyde (0.24 g, 2.26 mmol) and incubate at this temperature for 30 min.
Stir for hours. The reaction solution was added to a mixture of phosphate buffer (5 ml) of pH 7.0, methanol (11 ml) and 30% hydrogen peroxide (5 ml) at 0°C, and stirred for 1 hour. After methanol was distilled off under reduced pressure, the ether oil was extracted, and the extract was dried over anhydrous sodium sulfate, and then the ether was distilled off under reduced pressure. Add the residue to methanol (9 ml)
The mixture was dissolved in water, cooled to 0°C, added with sodium methoxide (28% methanol solution) (0.3 ml), and stirred for 5 minutes. The reaction solution was poured into saturated brine, extracted with dichloromethane, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane/ether = 7/3) to obtain a colorless oil (331 mg): yield 84% [α] ²⁵ _D (c0.12, CHCl ₃ ): -20.5°NMR ( _CDCl3 , ppm): 1.12 (d, 3H), 2.77 (m,
1H), 3.70 (s, 3H), 5.13 (d, 1H), 7.41
(s, 5H) Reference Example 3: Synthesis of N-butylbenzamide and benzaldehyde 3-1 3-benzoyl-2-thioxo-1,
3-Thiazolidine A solution of phenylchlorophosphonic-N-(2-thioxo-1,3-thiazolidide) (1.39 g, 5 mmol) in acetonitrile (50 ml) was added with benzoic acid (6.10 g, 5 mmol) and diisopropylethylamine ( 2.7 ml) was added and refluxed for 1 hour. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel chromatography (eluent: n-hexane/ethyl acetate =
3/1) to obtain yellow crystals (0.98 g): yield 88%, melting point 167-168°C NMR (CDCl ₃ , ppm): 3.45 (t, 2H), 4.54 (t,
2H), 7.25-7.80 (m, 5H) MS: m/e223 (M ⁺ ) 3-2 N-butylbenzamide 3-benzoyl-2-thioxo-1,3-thiazolidine (2.23 g, 0.01 mol) in dichloromethane ( n-butylamine (0.8 g, 0.011 mol) was added to dichloromethane (5 ml) solution under stirring at room temperature.
ml) solution and continued stirring until the initial yellow color disappeared. After evaporation of the solvent under reduced pressure, the residue was dissolved in a small amount of chloroform and purified by silica gel column chromatography containing 10% silver nitrate to obtain a colorless oily product (1.70 g): yield 96% NMR (CDCl ₃ , ppm): 0.91 (3H, t), 1.1-1.8
(4H, m), 3.37 (2H, q), 7.0~7.9 (6H,
m) 3-3 Benzaldehyde 3-benzoyl-2-thioxo-1,3-thiazolidine (112 mg, 0.5 mmol) was dissolved in an anhydrous mixed solvent of n-hexane (12 ml/dichloromethane (12 ml)) and heated to −50° C. under a nitrogen stream. °C, with stirring.
A 20% solution of diisobutylaluminum hydride in n-hexane (1 ml) was added dropwise, followed by continued stirring until the initial yellow color disappeared (approximately 5 minutes). A small amount of methanol was added to the reaction mixture, and the mixture was washed with an aqueous sodium carbonate solution and water, and then the solvent was distilled off under reduced pressure.
The residue was purified by silica gel column chromatography to obtain benzaldehyde (45 mg) as a colorless oil: yield 85%.

Claims (1)

[Claims] 1. General formula In the formula, R ¹ represents a phenyl group or a phenoxy group; R ² and R ³ each independently represent a hydrogen atom, a lower alkyl group, or a lower alkoxycarbonyl group; R ⁴ and R ⁵ each independently represent a hydrogen atom or a phenyl group; represents a group; X represents a chlorine atom; Y and Z each independently represent an oxygen or a sulfur atom. 2 General formula In the formula, R ¹ represents a phenyl group or a phenoxy group; X represents a chlorine atom; Y represents an oxygen or sulfur atom; In the formula, R ² and R ³ each independently represent a hydrogen atom, a lower alkyl group, or a lower alkoxycarbonyl group; R ⁴ and R ⁵ each independently represent a hydrogen atom or a phenyl group; Z represents an oxygen or sulfur atom. A general formula characterized by reacting the compound represented by in the presence of a base. In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , X, Y and Z have the above meanings.