JP2000219669A - Sulfonylation of alcohol - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a process for the sulfonylation of an alcohol on a laboratory or industrial scale in improved reactivity, economy, operability and environmental problem compared with conventional pyridine solvent process by sulfonylating an alcohol using a sulfonyl chloride and Et3N and RNMe2 catalyst. SOLUTION: An alcohol is sulfonylated by using a sulfonyl chloride (preferably p-toluenesulfonyl chloride or methanesulfonyl chloride) and preferably 1.5-2.5 equivalent of a catalyst comprising Et3N and RNMe2 (R is an alkyl, an arylalkyl or the like) (preferably 0.1-1.0 equivalent of Me3N). The reaction is carried out preferably by using dichloromethane, 1,2-dichloroethane, benzotrifluoride, acetonitrile or toluene as a solvent. The alcohol is preferably a primary or secondary alcohol (e.g. 1-octanol). Preferably, the reaction temperature is -10 to +10 deg.C and the reaction time is 1.0-5 hr.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a practical and economical process for the novel sulfonylation (including tosylation and mesylation) of alcohols, a fundamental and important reaction in organic synthesis. In particular, the present invention relates to a mixed amine dehydrochlorinating agent, Et ₃ N and RNMe ₂ [R represents an alkyl group, an arylalkyl group or a Me ₂ N (CH ₂ ) _n group (n
Is 3 to 6)] (or a salt thereof) (hereinafter simply referred to as “RNMe ₂ catalyst” or “RNMe ₂ ”
That. )).

[0002]

BACKGROUND OF THE INVENTION It has been recognized that the tosylation of alcohols is a fundamentally important reaction in various fields of organic synthesis, especially in the reaction of reliably converting alcohols to alkylating agents. Numerous tosylation methods (a) Sekera,
VC; Marvel, CSJ Am. Chem. Soc. 1933, 55, 34
5.b) Roos, AT; Gilman, H .; Beaber, NJ In Or
ganic Synthesis, 2nd ed .; Gilman, H., Ed .; Wiley:
New York, 1941; Col. Vol. 1, pp 145-147.c) Sekera,
VC; Marvel, CS Organic Synthesis; Wiley: Ne
w York, 1955; Col.Vol. 3, pp 366-367.d) Fieser
LF; Fieser, M. Reagent for Organic Synthesis; Wi
ley: New York, 1967; Vol 1., pp 1179-1184.e) Marc
h, J. Advanced Organic Chemistry; 4th ed .; Wiley:
See New York, 1992, pp 352-354. Other representative references include: f) Kabalka, GW; Varma, M .; Verma, R.
S .; Srivastava, PC; Knapp, Jr. FFJ Org. Ch
em. 1986, 51, 2386.g) Tanabe, Y .; Yamamoto, H .; Yo
shida, Y .; Miyawaki, T .; Utsumi, N. Bull. Chem. So
c. Jpn. 1995, 68, 297.)
Among them, a sulfonyl chloride and an alcohol are reacted in a pyridine solvent at a low temperature, and TsCl / pyridine (T
The s = p-toluenesulfonyl) reagent is traditionally and widely used (pyridine solvent method). However, this method has three significant problems.

[0003] The first problem is that during the tosylation reaction, a pyridine-HCl by-product is produced, which acts as a Cl-nucleophile, whereby the tosylate is converted to chloride and loss of the tosylate occurs. . This side reaction often occurs when an excess amount of a pyridine solvent is used or when the reaction temperature is high. A second problem is that generally more than equimolar pyridine (about 10 equivalents) is required for completion of tosylation. For this reason, removal of pyridine becomes complicated, and the load on the environment of wastewater increases.
A third problem is that a relatively long reaction time (10 hours or more) is required in the case of alcohol having low reactivity. Therefore, a new tosylation method for solving these problems is desired.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned problems of the conventional pyridine solvent method.

[0005]

Means for Solving the Problems The present inventors have conducted intensive studies to achieve the above object, and as a result, the mixed amine dechlorinating agents Et ₃ N and RNMe ₂ have excellent synergistic effects in sulfonylation. It was found that when these were used as catalysts, sulfonylation of various alcohols proceeded efficiently, and the present invention was completed. That is, the present invention relates to the sulfonylation of an alcohol, wherein the sulfonyl chloride is combined with Et ₃ N and the above-mentioned RNMe ₂
The present invention provides a method for sulfonylating an alcohol, which comprises using a catalyst.

[0006] The method of the present invention includes a method for tosylation and a method for mesylation of an alcohol. In the tosylation, p-toluenesulfonyl chloride (hereinafter, referred to as "TsCl") is used as a sulfonyl chloride. For the mesylation, methanesulfonyl chloride (hereinafter referred to as “MsC
l ". ) Is used. The method of the present invention can be roughly classified into the following two methods. (1) Sulfonyl chloride, Et ₃ N and RNM
How to use the e ₂ catalyst (hereinafter referred to as "method A".). (2) Sulfonyl chloride, inorganic base, Et ₃ N
And an RNMe ₂ catalyst (hereinafter referred to as “method B”). In the method of the present invention, a synergistic effect with Et ₃ N and RNMe ₂ was recognized, and the method of the present invention was more reactive and economical than the conventional pyridine solvent method, both in the laboratory and industrially. Excellent in operability, operability and environment.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The alkyl group of R in the RNMe ₂ catalyst includes an alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl and the like. Further, as the arylalkyl group,
An arylalkyl group having 7 to 12 carbon atoms, for example, benzyl, phenylethyl and the like can be mentioned. Also, RNMe
_{The two} catalysts may be used in the form of a suitable salt such as an HCl salt. In the case of Me ₃ N, it is preferably used as the HCl salt.

The alcohols capable of being sulfonylated by the method A of the present invention include various alcohols such as 1-octanol, 3-octanol, butanediol, lactate ester, epoxycitronellol, 2-hexen-1-ol and methallyl alcohol. Primary and secondary alcohols, and even sterically bulky alcohols such as menthol and 3,3-dimethylbutanol can be sulfonylated. As the solvent used, for example, dichloromethane, 1,2-dichloroethane, benzotrifluoride, acetonitrile, toluene and the like are preferable. Et ₃ N and R used
The amount of the NMe ₂ catalyst is not particularly limited, but is 1.5 to 2.5 equivalents, preferably 1.5 to 2.0 equivalents, and 0.1 to 1.0 equivalent, respectively, with respect to the alcohol. It is an equivalent, preferably 0.1 to 0.5 equivalent. The reaction temperature is -20 to 20C, preferably -10 to 10C, and the reaction proceeds even at a low temperature of 0 to 5C. Also,
The reaction time is 0.5 to 10 hours, preferably 1.0 to 5 hours.
The reaction is almost complete even within one hour.

As shown in the following examples, the method A of the present invention has a higher reaction rate and is more efficient than the conventional pyridine solvent method, and can rapidly tosylate primary and secondary alcohols. it can. In addition, in the method A, conversion to chloride, which is an undesirable side reaction, is extremely unlikely to occur,
Et ₃ N and RNMe ₂ exhibit a synergistic effect, and the tosylation efficiency is higher than that of the pyridine solvent method. Furthermore, the reaction of methallyl alcohol, an unstable allylic substrate, proceeds successfully, in contrast to the pyridine solvent method. That is, compared to the pyridine / HCl salt, RNMe ₂ has extremely low nucleophilicity and does not have the disadvantage of the pyridine solvent method.

[0010] From the above, the method A is characterized by (1) a high reaction rate, (2) safe production of tosylate,
(3) Easy operation. (4) Et ₃ N is less expensive than pyridine, and RNMe ₂ is not expensive. Tosylation method.

The method B of the present invention comprises the steps of:
Ruchloride, inorganic base, Et _ThreeN and RNMe_Two
A sulfonylation using a catalyst. Environmental in recent years,
Due to economic issues, BOD (Biochemical Oxygen Demand) or
Is an amine base with a large COD (chemical oxygen demand) value
It is desired to reduce the amount of
According to the report, sulfonylation of alcohol can be achieved with a small amount of amine.
It can be carried out.

Examples of the alcohol which can be sulfonylated by the method B include 1-octanol, 9-decene-
1-ol, ethylhexanoate-6-ol, 2-
Various primary alcohols such as hexen-1-ol are mentioned. As the solvent to be used, for example, 1,2-dichloroethane, acetonitrile, toluene and the like are preferable. The amount of Et ₃ N and RNMe ₂ catalyst used in this method is usually the alcohol, respectively 0.1-1.
0 equivalents, preferably 0.1 equivalents, and 0.1-1.
It is 0 equivalent, preferably 0.1 equivalent. Further, the reaction temperature is -10 to 30C, preferably 0 to 20C,
The reaction time is 1 to 10 hours, preferably 1 to 5 hours. The inorganic base used is, for example, KOH, K ₂ CO ₃ , C
a (OH) ₂ , CaO, Mg (OH) _2, and MgO are preferable, and KOH or Ca (OH) ₂ is particularly preferable. Method B has a lower reaction rate than method A, but is an environmentally friendly reaction in that amine can be catalyzed.

The above method A can be applied to a methanesulfonylation (mesylation) reaction. In ordinary mesylation, the reaction rate is high, so that a halogenated solvent (eg, CH ₂ C
l ₂ ) or an ether solvent (eg, ether, TH
F). However, recent experimental demands,
Particularly in view of requirements in industrial production, a reaction in a toluene solvent is desired. According to the method of the present invention, for example, using 1.5 equivalents of Et ₃ N and 0.1 equivalents of Me ₃ N, it was shown that tosylation in toluene was possible (see Example 5). ). As in the case of the tosylation reaction, the use of Et ₃ N alone hardly causes a mesylation reaction, and here, a synergistic effect of Et ₃ N and Me ₃ N is observed.

[0014]

EXAMPLES The present invention will now be described in more detail with reference to the following Examples, but it should not be construed that the invention is limited thereto. In the sulfonylation reaction in each example, commercially available TsC
l was recrystallized from EtOAc before use. Commercially available Me ₃
The N.HCl was dried under reduced pressure for several minutes.

Example 1 Tosylation reaction of alcohol using method A (1) General method of method A TsCl (1.2 to 1.5 mm) in a solvent (1.0 ml)
ol) with alcohol (1.0 mmol), Et ₃ N
(1.5-2.5 mmol) and RNMe ₂ (0.1
Or 1.0 mmol) to a stirred solution in a solvent (1.0 ml) at 0-5 ° C. and stir the mixture for 1 hour.
To decompose excess TsCl, N, N-dimethylethylenediamine (about 130 mg) was added to the mixture and 10
Stir for minutes. (If TsCl can be easily separated by column chromatography, this step is not necessary.) Water is added to the mixture and extracted with EtOAc. The organic phase is washed with water and brine, dried (Na
₂ SO ₄ ) and concentrate. The obtained crude product is subjected to silica gel column chromatography (hexane / ether = 30 to
10: 1) to give the desired tosylate.

(2) Tables 1 and 2 show the results of tosylation by method A using various alcohols. In addition,
The reaction using the conventional pyridine solvent method shown in 1-m was performed as follows. 3-octanol (130 mg, 1.
0 mmol) pyridine (870 mg, 11 mmol)
The solution was added to TsCl (286 m
g, 1.5 mmol) was added slowly. The reaction mixture was stirred at the same temperature for 1 hour, poured into water and extracted twice with ether. The organic layer was washed three times with a 1N aqueous solution of hydrochloric acid and then with a saturated saline solution, dried over Na ₂ SO ₄ , and then the solvent was distilled off under reduced pressure to obtain a crude product. This was purified by silica gel column chromatography (hexane / ethyl acetate = 20: 1) to give 3
-Octyl p-toluenesulfonate (1) (110
mg, 40%).

[0017]

[Table 1]

[0018]

[Table 2] used a) 1,2-dichloroethane, b) benzotrifluoride, c) pyridine (Py) in place of Et ₃ N, d) conventional pyridine solvent process (3-octanol to 11 eq), e) 4- Dimethylaminopyridine, f)
Reaction time is 3 hours, g) Reaction time is 5 hours.

As is clear from Tables 1 and 2, the following were shown as the characteristics of the method A of the present invention. (I) From screening of solvents performed using 3-octanol (No. 1), dichloromethane, 1,2-dichloroethane, benzotrifluoride (Ogawa, A .; Cur
ran, DPJ Org. Chem 1997, 62, 450), acetonitrile and toluene have been shown to be suitable as solvents. Under the same conditions as number 1-a in Table 1, DME, dioxane, THF, methyl isobutyl ketone were not suitable. (Ii) The alcohol tested was rapidly tosylated at 0-5 ° C. within one hour. (Iii) 1.5~2.5 Et ₃ N and 0.1 equiv
1.0 equivalent of Me ₃ N.HCl was required for tosylation. (Iv) In the absence of the Me ₃ N · HCl catalyst, the rate of the tosylation reaction was very slow (No. 1-j). From this, a synergistic effect of the Et ₃ N and Me ₃ N · HCl catalysts is observed. (V) In the case of 3-octanol, when pyridine is used instead of Et ₃ N (No. 1-k, 1), when tosylation is performed by the conventional pyridine-solvent method (No. 1-m), The rate has dropped. DM instead of Me ₃ N · HCl catalyst
Using AP (4-dimethylaminopyridine, an effective acylation catalyst) as a catalyst was also inefficient (number 1-n). (Vi) Even the less reactive 3,3-dimethylbutan-2-ol was tosylated within 5 hours (number 9).

Example 2 Tosylation of alcohol using various RNMe ₃ catalysts Tosylation of ₃ -octanol was carried out using the general method of Method A shown in Example 1. Table 3 shows the results.

[0021]

[Table 3]

Table 3 shows that the use of an alkyl group, an arylalkyl group, or a Me ₂ N (CH ₂ ) _n group as R in RNMe ₂ enables efficient sulfonylation of alcohol.

Example 3 Comparison of Method A with Pyridine Solvent Method (1) Tosylation of 1-octanol by pyridine solvent method TsCl (286 mg, 1.5 mmol) was converted to 1-octanol (130 mg, 1.0 mmol) of pyridine ( 0.87 ml) to the stirred solution at 0-5 <0> C,
The mixture was stirred at 30 ° C. for 2 hours. The usual treatment of this method gave a crude product (275 mg). this is,
^{By 1} H NMR (400 MHz), 1-octyl tosylate (51%) and 1-chlorooctane (43%)
(See a) to e) above). (2) Methallyl (2-methyl-2) by pyridine solvent method
Reaction of -propenyl) alcohol TsCl (286 mg, 1.5 mmol) was added to a stirred solution of methallyl alcohol (72 mg, 1.0 mmol) in pyridine (0.87 ml) at 0-5 <0> C,
The mixture was stirred for 1 hour. The usual treatment of this method gave the crude product (45 mg) (see a) to e) above). It contained a small amount of metalyltosylate and mainly TsCl recovered. (3) Tosylation of 1-octanol and methallyl alcohol using Method A was performed according to the general method of Method A of Example 1. (4) The results are shown in Scheme 1.

[0024]

Embedded image

The results shown in Scheme 1 show that Method A can significantly reduce the conversion of tosylate to chloride as a side reaction and has a very high tosylation efficiency as compared with the conventional pyridine solvent method. Was. Further, in the tosylation reaction of methallyl alcohol, under conditions of 1 hour at 0 to 5 ° C., almost no tosylate was obtained by the pyridine solvent method, whereas in method A, the tosylate was efficiently obtained. This indicates that the use of method A enables tosylation of a sterically bulky alcohol more efficiently than the pyridine method.

Example 4 Tosylation of Alcohol Using Method B (1) General Method of Method B TsCl (1.5 mmol) in a solvent (1.0 ml)
With an alcohol (1.0 mmol), an inorganic base (1.5
_{~3.0mmol), Et 3 N (10mg} , 0.1mm
ol) and RNMe ₂ (0.1 mmol) to a stirred suspension in a solvent (1.0 ml) at 0-5 ° C.
The mixture is stirred for 1 hour and further at room temperature for 3-5 hours. Aqueous 1M HCl was added to the mixture and EtOAc was added.
Extract with The desired tosylate is obtained by the same treatment and purification as in method A. Here, the inorganic base was converted into a dispersion to be used by refluxing KOH in pellets for about 0.5 hour in toluene. Granular Ca (OH) ₂ was used. (2) Table 4 shows the results of tosylation by method B using various inorganic bases of 1-octanol.

[0027]

[Table 4] a) No Et ₃ N b) No Me ₃ N · HCl

As a result, the following were shown as features of the method B of the present invention. (I) KOH and Ca (OH) ₂ were superior to other inorganic bases; with Mg (OH) ₂ and MgO, the conversion was <20%. (Ii) Et ₃ N and Me ₃ N · HCl as in method A
Was observed, and in the absence of the Me ₃ N · HCl catalyst, the rate of the tosylation reaction was very slow. (Iii) Strong bases [KOH and Ca (OH) ₂ ] tosylate the primary alcohol compared to the relatively acidic 2-alkenyl (alkynyl) alcohol using K ₂ CO ₃ base (g above). Is preferred.

(3) KOH or Ca (OH) as a base
Table 5 shows the results of testing the tosylation of some primary alcohols by Method B based on the results of (2), tosylation of various alcohols by Method B using Method ₂ .

[0030]

[Table 5]

In the method B, the reaction of the secondary alcohol such as 2-octanol and 3-octanol takes a long reaction time (0 to 5 ° C., 1 hour and room temperature, 10 hours).
Was not completed (<about 50%).

Example 5 Mesylation with MsCl / Et ₃ N and Me ₃ N.HCl MsCl (172 mg,
1.5 mmol) with alcohol (1.0 mmol), E
t ₃ N (1.5 or 2.0 mmol) and Me ₃ N
To a stirred solution of HCl (0.1 or 1.0 mmol) in toluene (1.0 ml) at 0-5 <0> C and the mixture was stirred for 1 hour. Similar treatment and silica gel column chromatography (hexane / EtOAc = 5:
According to 1), a desired mesylate was obtained. Table 6 shows the results of the mesylation reaction of 3-octanol and 3,3-dimethyl-2-butanol.

[0033]

[Table 6] a) 4-dimethylaminopyridine b) Reaction time is 5 hours

The results show that the sulfonylation method of the present invention can be applied to efficiently perform tosylation using toluene as a solvent. In contrast, as shown by 1-c, without the addition of Me ₃ N · HCl, the yield of 3-octyl methanesulfonate objective was 10% or less.

The physical properties of each tosylate obtained by the method of the present invention are shown below. Melting points were measured on a hot stage microscope (Yanagimoto) and are uncorrected. ¹ HNM
R spectra were recorded on a JEOL EX90 (90 MHz) and / or JEOLα (400 MHz) spectrometer in CDCl ₃ using a TMS internal standard. The IR spectrum was measured using JASCO FT / IR-80.
Recorded on a 00 spectrophotometer. Silica gel column chromatography was performed using Merck Art. 773
4 and / or 9385.

[0036] 3-octyl p- toluenesulfonate (1) a colorless _{^{oil: 1 HNMR (90MHz, CDC1 3}} ) δ0.8
0 (3H, t, J = 7.7 Hz), 1.01-1.82
(13H, m), 2.42 (3H, s), 4.38-
4.62 (1H, m), 7.22-7.48 (2H,
m), 7.71-7.89 (2H, m); IR (film) 2957, 2934, 2864, 1597, 146
0, 1364, 1188, 1177, 1098, 910
cm ^-1 .

1-octyl p-toluenesulfonate (2) colorless oil: ¹ H NMR (90 MHz, CDCl ₃ ) δ 0.8
7 (3H, t, J = 7.2 Hz), 1.08-1.82
(12H, m), 2.44 (3H, s), 4.03 (2
H, t, J = 6.9 Hz), 7.24-7.49 (2
H, m), 7.72-7.91 (2H, m); IR (film) 2928, 2857, 1599, 1466, 1
362, 1177, 1098, 949, 910 cm ^-1 .

[0038] 9-decenoic-yl p- toluenesulfonate (3) a colorless _{^{oil; 1 HNMR (90MHz, CDC1 3}} ) δ0.7
8-2.18 (14H, m), 2.44 (3H, s),
4.02 (2H, t, J = 7.7 Hz), 4.81−
5.12 (2H, m), 5.58-6.04 (1H,
m), 7.22-7.44 (2H, m), 7.72-
7.91 (2H, m); IR (film) 2928, 1
639, 1599, 1362, 1177, 937c
m ^-1 .

Ethyl 6- (p-toluenesulfonyloxy) hexanoate (4) Colorless oil: ¹ H NMR (90 MHz, CDCl ₃ ) δ 1.2
4 (3H, t, J = 7.7 Hz), 1.34-1.83
(6H, m), 2.25 (2H, t, J = 7.7H
z), 2.45 (3H, s), 3.91-4.28 (4
H, m), 7.23-7.44 (2H, m), 7.70
-7.92 (2H, m); IR (film) 2942,
1734, 1458, 1360, 1177, 1030,
951 cm ^-1 .

[0040] 2-octyl p- toluenesulfonate (5) a colorless _{^{oil: 1 HNMR (90MHz, CDC1 3}} ) δ0.8
2 (3H, t, J = 7.2 Hz), 0.99-1.69
(13H, m), 2.41 (3H, s), 4.41-
4.79 (1H, m), 7.20-7.42 (2H,
m), 7.68-7.89 (2H, m); IR (film) 2932, 2861, 1599, 1460, 136
2, 1175, 1098, 914 cm ^-1 .

Bis (p-toluenesulfonyloxy) butane (6) colorless crystals: melting point 57.5-58.5 ° C .; ¹ HNMR (9
0 MHz, CDC1 ₃ ) δ 0.82 (3H, t, J =
7.7 Hz), 1.48-1.81 (2H, m), 2.
47 (6H, s), 4.02 (2H, d, J = 6.8H)
z) 4.40-4.71 (1H, m), 7.19-
7.48 (4H, m), 7.59-7.91 (4H,
m); IR (KBr) = 2976, 1597, 146
0, 1362, 1194, 1179, 909 cm ^-1 . Calcd _{C 16 H 22 O 6 S 2} : C, 54.25; H,
5.56. Found: C, 54.0; H, 5.4.

1-menthyl p-toluenesulfonate (7) colorless crystal: melting point 92.5-93.5 ° C .; ¹ H NMR (9
0 MHz, CDCl ₃ ) δ 0.52 (3H, d, J =
6.4 Hz), 0.70-2.27 (15H, m),
2.42 (3H, s), 4.23-4.56 (1H,
m), 7.23-7.43 (2H, m), 7.71-
7.91 (2H, m); IR (film) 2963,2
936, 1599, 1454, 1358, 1179, 1
098, 943, 910 cm ^-1 .

[0043] Methyl 2-(p-toluenesulfonyloxy) propionate (8) a colorless _{^{oil: 1 HNMR (90MHz, CDC1 3}} ) δ1.5
2 (3H, d, J = 7.7 Hz), 2.44 (3H,
s), 3.68 (3H, s), 4.98 (1H, q, J
= 7.7 Hz), 7.22-7.43 (2H, m),
7.74-7.92 (2H, m); IR (film) 2
957, 1761, 1451, 1370, 1190, 1
179, 1084, 926 cm ^-1 .

3,3-dimethylbutan-2-yl p-
Toluenesulfonate (9) a colorless _{^{oil: 1 HNMR (400MHz, CDC1 3}} ) δ0.
84 (9H, s), 1.21 (3H, d, J = 6.8H)
z), 2.44 (3H, s), 4.39 (1H, q, J
= 6.4 Hz), 7.31-7.33 (2H, m),
7.78-7.80 (2H, m); IR (film) 2
971, 1599, 1480, 1362, 1177, 1
074, 901 cm ^-1 .

[0045] 3,7-dimethyl-6,7-epoxy-octyl p- toluenesulfonate (10) a colorless _{^{oil: 1 HNMR (90MHz, CDC1 3}} ) δ0.8
5 (3H, d, J = 7.0 Hz), 1.25 (3H,
s), 1.29 (3H, s), 1.10-1.80 (7
H, m), 2.45 (3H, s), 2.65 (1H,
t, J = 7.0 Hz), 4.10 (2H, d, J = 7.
0 Hz), 7.20-7.45 (2H, m), 7.70
-7.90 (2H, m); IR (film) 2961;
1360, 1177, 1098 cm ^-1 . Calcd _{C 17 H 26 O 4 S:} C, 62.55; H, 8.03. Found: C, 62.3; H, 7.7.

2-Hexin-1-ol p-toluenesulfonate (11) Colorless oil: ¹ H NMR (90 MHz, CDCl ₃ ) δ 0.9
0 (3H, t, J = 7.0 Hz), 1.20-1.65
(2H, m), 1.90-2.30 (2H, m), 2.
45 (3H, s), 4.70 (2H, s), 7.20-
7.45 (2H, m), 7.70-7.90 (2H,
m); IR (film) 2967, 2240, 136
4, 1175, 1098 cm ^-1 . Elemental analysis: Calculated C _{13
H l6 O 3 S: C,} 61.88; H, 6.39. measured value:
C, 61.6; H, 6.1.

Methallyl (2-methyl-2-propenyl)
p-Toluenesulfonate (12) colorless oil: ¹ H NMR
_{(90MHz, CDC1 3) δ1.70 (} 3H, s),
2.45 (3H, s), 4.45 (2H, s), 4.8
9-5.06 (2H, m), 7.21-7.47 (2
H, m), 7.70-7.91 (2H, m); IR (film) 2980, 2949, 1599, 1360, 1
171, 934, 816 cm ^-1 .

3-octyl methanesulfonate (1
3) a colorless _{^{oil: 1 HNMR (400MHz, CDC1 3}} ) δ0.
90 (3H, t, J = 7.2 Hz), 0.99 (3H, t, J = 7.2 Hz)
t, J = 7.2 Hz), 1.22-1.81 (10H,
m), 3.03 (3H, s), 4.64-4.72 (1
H, m); IR (film) 2938, 2872, 13
50, 1175, 918 cm ^-1 .

[0049] 3,3-Dimethyl-2-yl methanesulfonate (14) a colorless _{^{oil: 1 HNMR (400MHz, CDC1 3}} ) δ0.
99 (9H, s), 1.40 (3H, d, J = 7.2H
z), 3.01 (3H, s), 4.51 (1H, q, J
= 7.2 Hz); IR (film) 2969, 287
8, 1350, 1175, 905 cm ^-1 .

[0050]

As described above, the sulfonylation method of the present invention has high reactivity, economic efficiency,
In terms of operability and environment, this is a sulfonylation method superior to the conventional pyridine solvent method, which enables sulfonylation of a sterically bulky alcohol, and also enables mesylation using toluene as a solvent.

Continuation of the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (reference) C07D 303/16 C07D 303/16 // C07B 61/00 300 C07B 61/00 300 F term (reference) 4C048 AA01 BB02 CC01 XX02 4G069 AA15 BA21A BA21B BE01A BE01B BE14A BE14B BE33B CB61 4H006 AA02 AC61 BA02 BA06 BA29 BA51 BA69 BB11 BB12 BB21 BC32 4H039 CA66 CD10 CD20 CE10

Claims (13)

[Claims] In the sulfonylation of an alcohol, a sulfonyl chloride and a catalyst of Et ₃ N and RNMe ₂ (or a salt thereof) [R is an alkyl group, an arylalkyl group or a Me ₂ N (CH ₂ ) _n group (n is 3-6).] A method for sulfonylating alcohols. 2. The method according to claim 1, wherein the sulfonylation of the alcohol is carried out using a Me ₃ N (or a salt thereof) catalyst as the RNMe ₂ catalyst. 3. The method according to claim 1, wherein the tosylation of the alcohol is carried out using p-toluenesulfonyl chloride as the sulfonyl chloride. 4. The method according to claim 1, wherein mesylation of the alcohol is carried out using methanesulfonyl chloride as the sulfonyl chloride. 5. A solvent comprising dichloromethane, 1,2-
5. The method according to claim 1, wherein dichloroethane, benzotrifluoride, acetonitrile or toluene is used.
The method described in one. 6. The process according to claim 1, wherein 1.5 to 2.5 equivalents of Et ₃ N and 0.1 to 1.0 equivalent of Me ₃ N (or a salt thereof) catalyst are used. The described method. 7. The method according to claim 1, wherein the alcohol is a primary or secondary alcohol. 8. The method according to claim 1, further comprising using an inorganic base. 9. KOH or Ca (O (O) as an inorganic base
9. The method according to claim 8, wherein H) ₂ is used. 10. The process according to claim 8, wherein 0.1 equivalent of Et ₃ N and 0.1 equivalent of Me ₃ N (or a salt thereof) catalyst are used. 11. The method according to claim 8, wherein the alcohol is a primary alcohol. 12. A compound comprising Et ₃ N and RNMe ₂ [R is selected from an alkyl group, an arylalkyl group or a Me ₂ N (CH ₂ ) _n group (n is 3 to 6)] or a salt thereof. Catalyst for sulfonylation of alcohol. 13. The method of claim 12, wherein RNMe ₂ is Me ₃ N.
The catalyst as described.