JPS62209035A - Production of diol derivative - Google Patents

Abstract

PURPOSE:To easily obtain the titled compound useful as a synthetic raw material for vitamin A, in high yield, from a hydroxylamine derivative of a novel compound which is easily available on an industrial scale at a low cost, by carrying out catalytic reaction of the derivative in the presence of zinc and an acid. CONSTITUTION:The objective compound of formula V can be produced by (1) reacting a chloroterpene alcohol of formula I (R<4> is H, lower alkanoyl or benzyl; n is 0 or 1) with a secondary amine of formula II (R<2> and R<3> are lower alkyl, etc.) and optionally esterifying the product to obtain the compound of formula III, (2) reacting the compound with an organic acid, etc., to obtain a novel compound of formula V (R<1> is R<4> except for H) and (3) subjecting a hydroxylamine derivative of the compound of formula IV to catalytic reaction at 10-100 deg.C in the presence of zinc and an acid such as acetic acid. USE:A synthetic intermediate for the production of oxoterpene alcohol of formula VI which is a synthetic raw material for vitamins useful as pharmaceuticals and feed additives.

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention relates to the production of diol derivatives represented by the general formula (wherein R1 represents a lower alkanoyl group or a benzyl group, and n represents an integer of O or 1). Regarding the method.

The diol derivative represented by the general formula (I) produced by the method of the present invention is useful as a raw material for the synthesis of vitamin C or its derivatives, which are used as medicines or feed additives. -butinal, 8-
It is useful as a synthetic intermediate for producing oxoterpene alcohol derivatives such as acetoxy-2,6-dimethyl-2,6-octagenal [e.g. (Angewandte Ch.
amie International Edition
in English) Volume 16 (1977), pp. 423-429; Chemistry-vp-s (Cht.
ai atry Letters) 1985, 1st
See pages 883-1886, etc.].

[Conventional technology]

It has been known that several types of diol derivatives represented by the general formula (1) can be produced by the following methods.

(1) Preparation of 8-acetoxy-2,6-dimethe-2,6-octalenin-1-ol by oxidizing 3,7-dimethyl-2,6-octadininyl acetate with selenium dioxide and t-butyl peroxide. Manufacturing method: [Journal of the American Chemical-7 Society]
can Chemical Society) Volume 99 (
(1977), pp. 5526-5528] (2) Terpene alcohol derivative 4 was added to benzene sulfate 7
A method for producing diol derivatives by using the addition product obtained by reacting with enyl chloride as a synthetic intermediate: (The middle person in the above formula represents an acetyl group or a benzyl group, m
represents an integer of O or 1) [Tetrahedron Letters
Latters) 1978, @4539-4542
See page] [Problems to be Solved by the Invention] The above conventional methods have problems in producing diol derivatives in one go. That is, in the method (1) above, the selenium dioxide used is toxic and has sublimation properties, so strict care must be taken when handling it. Furthermore, benzenesulfenyl chloride used in the method (2) above is expensive.

Therefore, an object of the present invention is to provide a method for easily producing a diol derivative represented by the general formula (1) in a high yield from inexpensive and easily available industrial raw materials.

[Means for solving problems]

According to the invention, the above object is achieved by the general formula (wherein R2 and R3 each represent a lower alkyl group or together represent a tetramethylene group, and R1 and n are as defined above) This is achieved by providing a method for producing a diol derivative represented by the general formula (1), which comprises contacting the hydroxylamine derivative represented by the formula (1) with zinc in the presence of an acid.

Examples of the lower alkanoyl group represented by 81 in the above general formula include formyl group, acetyl group, glopionyl group, and butyryl group, and examples of the lower alkyl group represented by R2 and R3 include methyl group, ethyl group, and propyl group. , isopropyl group, butyl group, inbutyl group, etc.

The zinc used in the production reaction of the diol derivative represented by the general formula (1) according to the present invention includes the general formula (II
) It is preferable to use zinc powder that has a large contact area with the hydroxylamine derivative. Although a commercially available zinc powder may be used as it is, it is preferable to use one whose surface has been activated by contacting it with an acid such as dilute hydrochloric acid. The amount ranges from about 1 to 30 moles per mole of submers.

As the acid present in the reaction system, organic acids such as acetic acid, propionic acid, and formic acid are preferably used, and acetic acid is particularly preferably used. Preferably, the reaction is carried out in a mixed solvent of acid and water in a molar ratio of about 1:30 to about 3:1. This mixed solvent is preferably used in an amount such that the concentration of the hydroxylamine derivative represented by the general formula (If) is about 0.01 to 1 mol/I. This reaction is preferably carried out at a temperature in the range of about 10-100°C.

The diol derivative represented by the general formula (1) obtained by the above reaction can be separated and purified from the reaction mixture, for example, by the following method. For example, after neutralizing the reaction mixture as necessary, the reaction mixture is extracted with chloroform, diethyl ether, etc., the solvent is distilled off from the extract, and the resulting residue is subjected to purification operations such as distillation or column chromatography. The diol derivative represented by the general formula (1) can be obtained by adding the diol derivative represented by the general formula (1).

General formula (
The hydroxylamine derivative represented by II) is a new compound that has not been published in any literature, and is represented by α (in the formula, 84 represents a hydrogen atom, a lower alkanoyl group, or a benzyl group, and n is as defined above). By reacting the chloroterpene alcohol a with a secondary amine represented by the general formula (wherein R2 and R3 are as defined above) and optionally esterifying the product, the general formula ( In the formula, R1, B2, R3 and n are as defined above. It can be obtained by reacting with and heat-treating the resulting product.

By reacting the chloroterpene alcohol represented by the general formula (■) with the secondary amine represented by the general formula (IV), the general formula % formula % (wherein R2, R3, H4 and n are as defined above) An aminoterpene alcohol or a 〇--substituted derivative of H7 is obtained. The secondary aban represented by the general formula (F/) is usually used in an amount of 1 mol or more per 1 mol of the chloroterpene alcohol represented by the general formula (II). The reaction temperature can be normally selected within the range from 0°C to the boiling point of the secondary amine, but a range of about 20 to 50°C is particularly preferred. The reaction is carried out in the presence or absence of a solvent, such as water; lower aliphatic alcohols such as methanol and ethanol; nitriles such as acetonitrile;
Solvents that do not adversely affect reactions such as amides such as N,N-dimethylformamide can be used alone or in combination. Further, the secondary amine can be used in an amount in large excess with respect to the chloroterpene alcohol represented by the general formula (ln), so that the secondary amine can also serve as a solvent. In addition, when a chloroterpene alcohol in which R4 is a lower alkanoyl group in the general formula (ill) is reacted with a secondary amine represented by the general formula (IV) in the presence of water, a hydrolysis reaction occurs. and an aminotylpene alcohol in which R4 is a hydrogen atom in the general formula (V'), or an 〇-substituted azmethylpene alcohol derivative in which R4 is a lower alkanoyl group in the general formula (V') and the aminoterpene alcohol. A mixture of

The aminoterpene alcohol represented by the general formula (V') obtained by the reaction of the chloroterpene alcohol represented by the above general formula (fit) and the secondary amine represented by the general formula (IV), or its 〇-- Separation and purification of the converted derivative from the reaction mixture can be carried out, for example, by the following method. The reaction mixture is mixed with a basic aqueous solution such as an aqueous sodium hydroxide solution, extracted using a solvent such as diethyl ether, ethyl acetate, or benzene, the solvent is distilled off from the extract, and the residue is subjected to column chromatography. The aminoterpene alcohol represented by the general formula (V') or its O-substituted derivative can be obtained by subjecting it to purification operations such as the following.

The aminoterpene alcohol represented by the general formula (v') or its O-substituted derivative obtained in this manner is esterified as required to obtain an O-[substituted amino acid represented by the general formula (■)]. Converts to terpene alcohol derivatives. That is, by esterifying an aminoterpene alcohol in which R4 is a hydrogen atom in the general formula (V') with a lower alkanoic acid or a reactive derivative thereof according to a known method for esterifying a normal alcohol, the general formula In (g), R1 is converted into a conductor such as an 0-substituted aminoterpene alcohol, in which R1 is a lower alkanoyl group. For example, after dissolving an aminoterpene alcohol in which R4 is a hydrogen atom in general formula (v') in a solvent such as triethylamine, acetyl chloride, chloride, etc. By reacting with a lower alkanoic acid chloride such as propionyl or a lower alkanoic anhydride such as acetic anhydride or propionic anhydride, R1
An 〇-substituted aminoterpene alcohol derivative in which is a lower alkanoyl group can be produced. The 0-# substituted aminoterpene alcohol derivative in the general formula (V) obtained in this way, in which R1 is a lower alkanoyl group, can be separated and purified from the reaction mixture, for example, by mixing, extracting with diethyl ether, etc. Distill the solvent from the liquid,
By subjecting the residue to a purification operation such as column chromatography, a 0--substituted aminoterpene alcohol derivative of general formula (V) in which R1 is a lower alkanoyl group can be obtained.

General formula (II
) can be obtained. Examples of organic peracids used include aliphatic organic peracids such as peracetic acid, aromatic organic peracids such as perbenzoic acid and m-chloroperbenzoic acid, and the like. Further, hydrogen peroxide can be used in its water bath solution; for example, it is convenient to use a commercially available 30% aqueous solution as it is. The amount of organic peracid and hydrogen peroxide used is according to the general formula (V)
The amount is usually about 1 to 2 moles per mole of the 0-[converted aminoterpene alcohol derivative represented by
The reaction of the 0--substituted aminoterpene alcohol derivative represented by the general formula (V) with an organic peracid or hydrogen peroxide is preferably carried out in an amount of ~1.2 mol in the presence or absence of an organic solvent. However, in order to easily control the reaction, it is preferable to carry out the reaction in the presence of an organic solvent. Examples of such organic solvents include lower aliphatic alcohols such as methanol and ethanol; methyl acetate, vinegar ether;
Lower alkyl esters of lower aliphatic carboxylic acids such as methyl propionate; halogenated hydrocarbons such as methylene chloride, 1,2-dichloroethane, chloroform, and carbon tetrachloride; linear or cyclic such as diethyl ether, diimpropyl ether, and tetrahydrofuran. Examples include organic solvents that do not inhibit the reaction, such as ether. The reaction temperature is generally in the range of about -100°C to about 30°C, particularly preferably in the range of about -70°C to about 20°C.

The product obtained by this reaction can be separated from the reaction mixture by the following method. A crude product is obtained by mixing the reaction mixture with a basic aqueous solution such as a sodium bicarbonate aqueous solution, extracting with ethyl acetate, methylene chloride, diethyl ether, etc., and distilling off the solvent from the extract.

The heat treatment of the product obtained by the reaction of the 〇-substituted aminoterpene alcohol derivative represented by the above general formula (V) with an organic peracid or hydrogen peroxide is performed using a lower aliphatic compound such as methyl acetate, ethyl acetate, or methyl propionate. Lower alkyl ester of carboxylic acid; methylene chloride, 1. It can be carried out in the presence or absence of an organic solvent that does not have an adverse effect on the heat treatment, such as a halogenated hydrocarbon such as z-dichloroethane, chloroform, or carbon tetrachloride. In this case, a product obtained by extraction with an organic solvent as described above from a reaction mixture of an o-1f-substituted aminoterpene alcohol derivative represented by general formula (V) and an organic peracid or hydrogen peroxide. It is practical to heat-treat the extract containing . Heat treatment is usually about 40-150'GO
It is carried out at a range of temperatures.

The hydroxylamine derivative represented by the general formula (It) obtained by the above heat treatment is obtained by subjecting the reaction mixture to a purification operation such as column chromatography after distilling off the solvent, if necessary. Particularly, it is obtained separately.

In addition, the chloroterpene alcohols represented by the general formula (ffl) can be obtained by, for example, reacting the terpene alcohols represented by the general formula (in the formula, 84 and n are as defined above) with hypochlorous acid. [Tetrahedron Letter+s] 19 obtained in good yield by
1980, pp. 441-444].

The diol derivative represented by the general formula (1) provided by the method of the present invention is oxidized using a known oxidizing agent commonly used in the oxidation reaction of alcohol to aldehyde, such as manganese dioxide and chromic anhydride. In particular, it can be derived into an oxoterpene alcohol derivative represented by the general formula (in which R1 and n are as defined above) [for example, in the New Experimental Chemistry Course (No. 15) edited by the Chemical Society of Japan.
Volume)” (1976, Maruzen) pp. 71, 120, 352, 465, 471, 608, 8
See pages 25, 862, 877, 1034 and 1034].

〔Example〕

The present invention will be explained below with reference to Examples, but the present invention is not limited by these Examples. Reference Example I CHs (?H3 CHs C-CHCH2CH2C-CHCH20COC
Ha HOc′ α 3,7-dimethyl-2,6-octadininyl acetate 63.5 f (0,324 aoj) with methyl chloride vy
(Dissolved in 2.7t, saturated sulfuric acid) IJium aqueous solution 3
00x/ and 42f of bleaching powder (available chlorine 61%) were added.

This mixture was added to dry ice 2809 in portions under stirring while maintaining the reaction temperature below 10°C (
10 t dry ice pieces were added 10 times at 10 minute intervals, then 209 dry ice pieces were added 9 times at 10 minute intervals). After the addition of dry ice was completed, stirring was continued for an additional 2 hours while maintaining the reaction temperature at 10° C. or lower. The white precipitate was separated from the resulting reaction mixture, and the organic layer was separated from the F solution. This organic layer and an extract obtained by extracting water R3 with methylene chloride were combined and dried over anhydrous magnesium sulfate for 30 minutes. Methylene chloride was distilled off from the dried liquid under reduced pressure to obtain a residue of 66.32. This residue was analyzed by NMR spectrum and found to be 6-chloro-3,7-dimethyl-2.7-octacyenyl acetate with a purity of 89% (yield near 9%).

Example 1 Police Cf-l2=CCHCHz CH2sa=C11CH20
H(CH'C0)2゜N(CHs)2 CH3CH3 CH2=CHCH2CH2C=CHCH20COCHa
CH'C000H through N(CH3)2 CH3CH3 9HO-CH28=CHCH2CH2C=CHCH20
COCH3(IL) Purity 89% obtained in Reference Example 1
Add 1.849 (8.0 mmol) of 6-chloro-3,7-dimethyl-2,7-octacyenyl acetate to a mixed solution of 50a/5031R% dimethylamine aqueous solution and 8d ethanol, and heat at room temperature. Stirring was performed for 5 days. Dimethylamine and ethanol were distilled off from the resulting reaction mixture under reduced pressure, and 0% sodium hydroxide was added to the residue.
．． After adding a solution consisting of 5 t and 30 txl of water, the mixture was extracted with ether. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography [eluent: ethyl acetate/hexane (volume ratio) = 1/9 to 2/8] to obtain 6-(dimethylamino)-3,7-di! Chill-2
, 7-octacyen-1-ol was obtained in 1.39F (yield based on the used 6-chloro-3,7-dimethyl-2,7-octacyenyl acetate; 88%) 0''H-NMR (Cα4 /TMS) δ: 1.63 (6H,a), 1.6~2.2 (4H
, m), 2.13 (6H, s).

2.30 (IH,t, J=7Hz), 3.33
(IH, bs).

3.93 (2H, d, J=7Hz), 4.73 (2
H, bs).

5.23 (IH, t, J=7Hz) IR (film): 3350, 1440.1370, 1020°8
90 stroke 1 (b) 6-(dimethylamino)-3,7-dimethyl-2
．． 7-octarenin-1-ol 1.20f (6,1m
Dissolve mol ) in pyridine 2-, add 1.25 mol of acetic anhydride
' (12.3 mmol) was gradually added dropwise at room temperature, and stirring was continued for 2 days. After the reaction was completed, water and a saturated aqueous solution of 7 um hydrogen carbonate were added to the reaction mixture, and then the ether potato kidney solution was dried over anhydrous magnesium sulfate. After distilling off the solvent from the dry solution under reduced pressure, the residue was subjected to silica gel column chromatography [eluent: ethyl acetate/
Purified with hexane (volume ratio) = 1/9 to 515],
(dimethylamino)-3,7-dimethyl-2,7-octacyenyl acetate at 1.30? obtained [used 6
-(Dimethylamino)-3,7-dimethyl-2.7-octarenin-1-ol Yield based on: 89es3゜"H-NMR (Cα4/TMS) δ: 1.65.1.70 (each3H,s ) ;1.60
~2.00 (4H, m); 1.97 (3H, s);
2.15 (6H, a); 2.42 (IH, t, J=
6Hz); 4.50 (2H, d, J=7Hz); 4
．． 85 (2H, m); 5.29 (IH, t, J=7Hz
) IR (film): 1740, 1450, 1370,
1235°1020, 900eM (c) 6(dimethylamino)-3,7-dimethyl-2,
7-octadi x 2A/acetate 1.0r (4,2m
After adding 0.49 t of sodium carbonate to a solution of mol ) and 30 tJ of methylene chloride, a mixed solution of 0.88 f of peracetic acid, acetic acid and water containing 40% of peracetic acid was prepared at a temperature of -60°C with stirring. (4.6 mmol of peracetic acid) was gradually added dropwise. After the dropwise addition was completed, stirring was continued for 30 minutes at a temperature of -60°C, and then the temperature was gradually raised to 0°C. Add 251 ml of saturated aqueous sodium hydrogen carbonate solution to the resulting reaction mixture.
After adding Lt, the organic layer was separated, the aqueous layer was extracted with ethyl acetate, the organic layer and the extract were combined, and dried over anhydrous magnesium sulfate.

The obtained dry liquid was heated at a temperature of 50°C for 1 hour. After the heat treatment, the solution was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography [eluent: ethyl acetate/hexane (volume ratio) = 1/9 to 2/8]. 8-(dimethylaminooxy)-3
, 7-dimethyl-2,6-octadininyl acetate was obtained in an amount of 0.92 [6-(dimethylamino)-
Yield based on 3,7-dimethyl-2,7-octadininyl acetate; 86 yen].

1H-NMR (CC1a/TMS) 6:1.63
．． 1.70 (each 3H,s); 1.97 (3H
, s); 1.88-2.28 (4H, m); 2.5
0 (6H, s); 3.97 (2H, s); 4.5
3 (2H, d, J=7Hz); 5.35 (2H, t,
J=7Hz) IR (film) ν! 1740, 1440, 1380
．． 1230゜1120cts-'' (d) 1.02% zinc powder washed with 5% hydrochloric acid, water, methanol and ether and then dried was mixed with 8-(dimethylaminooxy)-3,7-dimethyl-2,6-octadi ”-Second acetate 0.30? (1,2 mmol
), acetic acid 15111 and water 15d, and the two mixtures were stirred at room temperature for 24 hours. Zinc dust was separated from the resulting reaction mixture and washed successively with 40 d of water and 50 d of chloroform.

The obtained P solution and washing solution were combined, neutralized with sodium carbonate, and then extracted with chloroform. After drying the extract with sodium carbonate, the solvent was distilled off under reduced pressure to obtain 0.247F of 8-hydroxy-3,7-dimether-2,6-octazininyl acetate (yield: quantitative). target).

Example 2 N(CHs)2 N(CHs)2 (Jk) 6-(dimethylamino)-3,7-dimethyl-2 obtained in the same manner as in Example 1(a) and (b)
．． 1 of 7-octadininyl acetate. Of (4
, 2 mmol) was dissolved in 30 d of methanol. Add to this solution 0.476f of 30% hydrogen peroxide solution at room temperature while stirring.
(4.2 mmol) was gradually added dropwise, and stirring was continued for 30 minutes at room temperature even after the dropwise addition was completed. The resulting reaction mixture was poured into water, extracted with ethyl acetate, and the extract was dried over anhydrous magnesium sulfate.

The obtained dry liquid was heated at a temperature of 50° C. for 1 hour. After the heat treatment, the solution was concentrated under reduced pressure, and the resulting 9 residue was purified by silica gel column chromatography [eluent: ethyl acetate/hexane (volume ratio) = 1/9 to 2/8]. -(dimethylaminooxy)-3,7
-Simethyl-2,6-octadininyl acetate at 0.
54 P gain [using 96-(dimethylamino)-3,
7-dimethyl-2.7-oc, yield based on tadienyl acetate: 51 qh).

(b) In the same manner as in Example 1(d), 8-hydroxy-3,7- 0.25 f of dimethyl-2,6-octadininyl acetate was obtained (yield: quantitative).

Reference Examples 2 to 3 α In Reference Example 1, 3,7-dimethyl-2.
6-octazininylbenzyl ether or 3-methyl-
The same procedure was carried out except that 0.324 moL of 2-butenylbenzyl ether was used to obtain the corresponding chloroterpene alcohol represented by the general formula (1). The purity and yield of the obtained chloroterpene alcohols are shown in Table 1.

Table 1 Example 3 (a) In Example 1(a), 6-chloro-3,
6-chloro-3,7-dimethyl-2.7-octacyenylbenzyl ether 2.48 S' (90% pure 6-chloro-3,7-dimethyl-2.7-octacyenylbenzyl ether obtained in Reference Example 2) was used instead of 7-dimethyl-2,7-octadininyl acetate. 8, Ommol)i was used, and N,N-dimethyl(5-
Benzyloxy-1-isopropenyl-4-methyl-4
-hexenyl)amine 1.61f was obtained (yield near 0%).
).

“H-NMR, (Cα4/TMS)δ.

1.63 (6H, s), 1.6-2.2 (4H, m
), 2.13 (6H, s).

2.33 (IHt t+ J-6Hz)-3-92
(2H+ d+ J=6Hz)-4,38(2H,s
), 4.77 (2H, b8).

5.30 (IH, t, J-6Hz), 7.17 (5H
, 5) IR (film): 1450, 1360, 10
70,1030°900m" (b) In Example 1(C), N,N-dimethyl(6-benzyl 8-benzyloxy-1
-(dimethylaminooxy)-2,6-dimethyl-2,
6-octadiene 1.02F was obtained (yield: 80%).

IH-NMR (Cα4/TMS) δ: 1.62 (6H, s), 2.0 to 2.3 (4) I, m
), 2.47(6H,')t3.95(2H,d,J=
6Hz), 3.97 (2H, s) 4.23 (2H,
8), 5.38 (2H,t, J-6Hz).

7.30 (5H, s) IR (film): 1670, 1450, 1360.
1170 Tan (e) In Example 1 (d), 8-(
dimethylaminooxy)-3,7-dimethyl-2,6-
8-benzyloxy-1-(dimethylaminooxy)-2,6-dimethyl-2,6-octadiz70.36F (1,2 mmol) instead of octadininyl acetate
The same operation was performed except for 9 using 8-benzyloxy-2,6-dimethyl-2,6-octarenin-1-ol 0.31F (yield: quantitative).

Example 4 H3 (a) In Example 1(a), 6-chloro-3,
2-chloro-3-fif-3-butenylbenzyl ether with a purity of 86% obtained in Reference Example 3 in place of 7-dimethyl-2,7-octazininyl acetate1.
The same operation was performed except that 96 f (8, Ommol) was used to prepare N,N-dimethyl(2-benzyloxy-
1.241 of 1-isopropenylethyl)amine was obtained (
Yield near 1ch) 0 1H-NMR (Cα4/TMS) δ: 1.63 (3H, s), 2.13 (6H, s), 2
．． 65 (IH, t, J=5Hz), 3.33 (2H,
s), 3.40 (2H, dd, J=5Hz.

J'=3Hz), 4.73(2H,s), 7.07
(5H, s) I R (Fill A) $/: 1450,1
360,1110,890crR-”(b) In Example 1(C), 6-(dimethylamino)-3,7-
N,N-dimethyl(2-benzyloxy-1-impropenylethyl)amine 0.929 (4,2mrno
4-benzyloxy-1-(dimethylaminooxy)-2-methyl-
Obtained 0.92f of 2-butene (yield: 93%) 1H-NMR (Cα4/TMS) δ: 1°57 (3H, s), 2.45 (6H, s), 3
．． 90 (2H, d, J=6.5I(z), 3.92
(2H,s), 4.33(2H,S).

5.42 (IH, t, J = 6.5Hz), 7.05 (
5H, 8) IR (film): 1690, 1455,
1070,1020cy++-' (C) Example 1 (
In d), 8-(dimethylaminooxy)-3,7
0.28 f (1,2 m
The same operation was carried out except that 4-benzyloxy-2-methyl-2-buten-1-ol was used (0. mol).
23f was obtained (yield: quantitative).

Example 5 (a) 6-chloro-3,7-dimethyl 2,7-octazininyl acetate 4.09 (15,
4 mmol), pyrrolidine 6.2 f/, sodium carbonate 5.51 and acetonitrile 50 MI were mixed, and 1
The mixture was heated under reflux for 6 hours. The resulting reaction mixture was filtered under suction, and pyrrolidine and acetonitrile were distilled off from solution F under reduced pressure. A saturated aqueous sodium bicarbonate solution was added to the residual solution, followed by extraction with ether, and the extract was dried over hot magnesium sulfate. The solvent was distilled off from the dry solution under reduced pressure, and the residue was subjected to silica gel column chromatography [eluent: ethyl acetate/hexane (volume ratio) = 2/8 to 1010].
), 3,7-dimethyl-6-(
1.31 of 1-pyrrolidinyl)-2,7-octazininyl acetate was obtained (yield based on 96-chloro-3,7-dimethyl-2,7-octazininyl acetate used: 32%) .

"H-NMR (Cα4/TMS) δ: 1.67 (6H, bs), 1.5-2.2 (9H
, m), 1.95 (3H, m).

2.1-2.6 (4H, m), 4.45 (2H, d,
J=7Hz).

7.76 (2H, s), 5.23 (IH, t, J=7
Hz) IR (film): 1740, 1370, 12
40,1120 pieces-1(b) In Example 1(C), 6-(dimethylamino)-3,7-dimethyl-2,
3,7-dimethyl-6-(1-pyrrolidinyl)-2,7-octazininyl acetate 1,11 instead of 7-octazininyl acetate? (4,2 mmol) was used, and 3,7-cymethyl-8
-(1-pyrrolidinyloxy)-2,6-octazininyl acetate tl-0,78? obtained [used 3,7-
Yield based on dimethyl-6-(1-pyrrolidinyl)-2,7-octazininyl acetate: 66%] 0 11 (-NMR (Cα4/TMS) δ: 1.68 (4
H,t, J=8Hz), 1.72(6H,s),
1.8-2.2 (4H1m) + 1-98 (3H1
') 12.88 (4) i, m), 4.02 (2H, s
), 4.50 (2H, d, J=7Hz), 5.35
(2H, t.

J=7Hz) (C) In Example 1(d), 3.7-dimethyl-8-(1- The same operation was carried out except that 0.34 t (1.2 mmol) of 8-hydroxy-3,7-dimethyl-2,6-octazininyl Aceter, ) f: 0.25
2 was obtained (yield: quantitative).

〔Effect of the invention〕

According to the present invention, as is clear from the above examples, the diol derivative represented by the general formula (I) can be easily produced in high yield from inexpensive and easily available industrial raw materials.

Claims (1)

[Claims] 1. General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (II) (In the formula, R^1 represents a lower alkanoyl group or a benzyl group, and R^2 and R^3 each represent a lower alkyl group. represents a group or together represents a tetramethylene group, n
represents an integer of 0 or 1) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I) (in the formula, R^ 1 and n are as defined above). 2. The hydroxylamine derivative represented by the general formula (II) has the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (III) (In the formula, R^4 represents a hydrogen atom, a lower alkanoyl group, or a benzyl group, and n are as defined above) are represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (IV) (where R^2 and R^3 are as defined above). By reacting with the secondary amine shown and esterifying the product as necessary, the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (V) (in the formula R^1, R^2, R A product obtained by obtaining an O-substituted aminoterpene alcohol derivative represented by The manufacturing method according to claim 1, which is obtained by heat-treating.