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CN120957968A - Synthesis of cyclic ketones from cyclic amino acids - Google Patents

Synthesis of cyclic ketones from cyclic amino acids

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Publication number
CN120957968A
CN120957968A CN202480024370.0A CN202480024370A CN120957968A CN 120957968 A CN120957968 A CN 120957968A CN 202480024370 A CN202480024370 A CN 202480024370A CN 120957968 A CN120957968 A CN 120957968A
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China
Prior art keywords
formula
compound
acid
salt
iii
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Inventor
J·R·比赛迪
A·拉米亚拉贾拉姆
B·G·皮莱
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Adama Makhteshim Ltd
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Makhteshim Chemical Works Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C249/02—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of compounds containing imino groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
    • C07C251/26—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having nitrogen atoms of imino groups further bound to halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/42—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydrolysis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

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  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

A process for preparing compounds of the formula (I) in which R is hydrogen, hydroxy, C1-C10-alkyl, C1-C10-alkoxy, C1-C4-alkylamino, di-C1-C4-alkylamino, C1-C4-acylamino, COOR1, -CH2-R2 in which R1 is hydrogen or C1-C4-alkyl or R2-CH 2-and R2 is hydroxy, C1-C4-alkoxy, C1-C4-alkylamino or di-C1-C4-alkylamino, n represents the number of carbon atoms and is any integer of 0, 1,2, and m represents the number of R groups and satisfies the following relation 0≤m≤8+2n. The process comprises (a) oxidizing a compound having the formula (III) wherein R is as defined above with a salt of a hypohalous acid to give a compound having the formula (II) wherein R, n and m are as defined above and X is Cl, br or I, and (b) hydrolyzing the compound having the formula (II) in the presence of water.

Description

Synthesis of cyclic ketones from cyclic amino acids
Technical Field
The present invention relates generally to a process for preparing cyclic ketones and more particularly to a novel route to 4-methoxycyclohexanone from cyclic amino acids, more particularly 1-amino-4-methoxycyclohexane-1-carboxylic acid.
Background
The use of cyclic ketones as starting materials in the synthesis of insecticidal, acaricidal and herbicidal compounds is known. They have important significance in the synthesis of cyclic ketoenols and in particular in the synthesis of spirotetramat.
Cyclic amino acids are generally obtainable by the synthesis of Bucherer-Bergs or by the synthesis of Style (Strecker), in each case yielding different isomeric forms. Conditions for the use of the synthesis of Buch-Bolus in the preparation of substituted cyclic amino acids of the general formula (1)
The cis isomer (1-a) is predominantly obtained, while the conditions for the Style synthesis predominantly give the trans isomer (1-b)
Wherein R 1 represents OR 2,R2 represents alkyl
The boolean-bordetes reaction is generally carried out by reacting a substituted cyclic ketone having the general formula (2):
wherein R 1 is defined above.
In a solvent or solvent mixture with ammonium carbonate and alkali metal cyanide, followed by isolation of the resulting hydantoin of formula (3):
Hydantoin is obtained as a mixture of the following cis (3 a) and trans (3 b) isomers:
the method may be illustrated, for example, by the following scheme:
Wherein R 1 represents OR 2 and R 2 represents an alkyl group.
The cis-trans mixture may be separated with aqueous ammonia, as defined in (US 7148377 B2).
Furthermore, the cis-trans spiro isomer mixture can be separated using a physical separation method, such as, for example, by column chromatography or fractional crystallization, and the cis spiro isomer can be separated as disclosed in US 7897803 B2.
Furthermore, in WO 2002/02532 and US 8710238 B2, the cis-trans hydantoin isomer mixture is treated with aqueous ammonia, and since the solubility of the cis salt is significantly lower than that of the trans salt, cis hydantoin can be separated in high purity by filtration while trans hydantoin remains in solution.
Furthermore, US 8710238 B2 discloses that the cis-isomer is separated when the cis-trans hydantoin isomer mixture is stirred with an aqueous solution of an alkali metal hydroxide or an alkaline earth metal hydroxide.
However, prior art processes produce cis hydantoin from cyclic ketones while producing unwanted trans hydantoin. This results in unsatisfactory yields. Furthermore, none of those prior art uses cis-trans mixtures of hydantoin compounds to produce cyclic ketones.
Thus, there is a need to develop a process for the production of cyclic ketones from cis-trans hydantoins.
Object of the Invention
The object of the present invention is to provide a process for the synthesis of cyclic ketones from cyclic amino acids via intermediate haloimines using oxidation followed by hydrolysis.
The object of the present invention is to provide a process for the preparation of a compound having formula (I):
Wherein R is hydrogen, hydroxy, C1-C10-alkyl, C1-C10-alkoxy, C1-C4-alkylamino, di-C1-C4-alkylamino, C1-C4-acylamino, COOR1, -CH2-R2, wherein R1 is hydrogen or C1-C4-alkyl or R2-CH 2-and R2 is hydroxy, C1-C4-alkoxy, C1-C4-alkylamino or di-C1-C4-alkylamino, n represents the number of carbon atoms and is any integer of 0, 1,2, and m represents the number of R groups and satisfies the following relation 0≤m≤8+2n.
The object of the present invention is to provide a compound having formula (II):
Wherein R, n and m are as defined above, and X is Cl, br or I.
Disclosure of Invention
According to one aspect, embodiments of the present invention disclose a process for preparing a compound having formula (I)
Wherein R is hydrogen, hydroxy, C1-C10-alkyl, C1-C10-alkoxy, C1-C4-alkylamino, di-C1-C4-alkylamino, C1-C4-acylamino, COOR1, -CH2-R2, wherein R1 is hydrogen or C1-C4-alkyl or R2-CH 2-and R2 is hydroxy, C1-C4-alkoxy, C1-C4-alkylamino or di-C1-C4-alkylamino, n represents the number of carbon atoms and is any integer of 0, 1,2, and m represents the number of R groups and satisfies the following relation 0≤m≤8+2n;
The method comprises the following steps:
(a) Oxidation of compounds of formula (III) with salts of hypohalous acids
Wherein R is as defined above to give a compound of formula (II)
Wherein R, n and m are as defined above and X is Cl, br or I, and
(B) Hydrolyzing the compound having formula (II) in the presence of water.
In one embodiment, the compound having formula (III) comprises the trans isomer.
In another embodiment, the compound having formula (III) comprises 99% cis isomer and 1% trans isomer.
In another embodiment, the compound having formula (III) comprises 1% cis isomer and 99% trans isomer.
In another embodiment, the compound having formula (III) comprises various ratios of cis to trans, for example, about 35:65 to about 99:1.
According to another aspect, embodiments of the present invention disclose a compound having formula (II)
Wherein R, X and n are as defined above, m represents the number of R groups and satisfies the relationship 1≤m≤8+2n and at least one R substituent is C1-C4-alkoxy.
According to another aspect, embodiments of the present invention disclose a process for preparing a compound having formula (II)
The method comprises the following steps:
(a) Oxidation of compounds of formula (III) with salts of hypohalous acids
Wherein R, X and n are as defined above, m represents the number of R groups and satisfies the relationship 1≤m≤8+2n and at least one R substituent is C1-C4-alkoxy.
Drawings
The figures illustrate various embodiments of systems, methods, and embodiments of various other aspects of the present disclosure. Those of ordinary skill in the art will understand that an element boundary (e.g., a box, group of boxes, or other shape) illustrated in the figures represents one example of a boundary. It is possible that in some examples, one element may be designed as a plurality of elements, or a plurality of elements may be designed as one element. In some examples, an element shown as an intrinsic component of one element may be implemented as an extrinsic component of another element, and vice versa. Furthermore, elements may not be drawn to scale. Non-limiting and non-exhaustive descriptions are described with reference to the following figures. The components in the drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles.
FIG. 1 shows 1 H NMR spectra of N-chloro-4-methoxycyclohexane-1-imine according to examples.
FIG. 2 shows 13 C NMR spectra of N-chloro-4-methoxycyclohexane-1-imine according to an example.
Figures 3 and 4 show Gas Chromatography (GC) of N-chloro-4-methoxycyclohexane-1-imine according to an example.
Fig. 5-9 show gas chromatography-mass spectrometry (GC-MS) spectra of N-chloro-4-methoxycyclohexane-1-imine according to embodiments.
Detailed Description
Some embodiments of the present disclosure exhibiting all of its features will now be discussed in detail. The words "comprise", "have", "contain" and "include" and other forms thereof are intended to be equivalent in meaning and be open ended, as the term "one or more items following any of these words is not intended to be an exhaustive list of such one or more items, or is intended to be limited to only the listed one or more items. It should also be noted that, as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Although any systems and methods similar or equivalent to those described herein can be used in the practice or testing of embodiments of the present disclosure, the preferred systems and methods are now described.
Embodiments of the present disclosure will be described more fully hereinafter with reference to the accompanying drawings, in which like reference numerals refer to like elements throughout the several views, and in which example embodiments are shown. The embodiments of the claims may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. The examples set forth herein are non-limiting examples and are merely examples of other possible examples.
The present invention relates to a process for preparing a compound having formula (I)
The process comprises two steps of oxidizing a compound having the formula (III) with a salt of a hypohalous acid
To obtain a compound of formula (II)
The compound of formula (II) is then hydrolysed in the presence of water.
The method according to the invention can be illustrated, for example, by the following scheme:
In one embodiment, the process may be used to prepare various compounds having the formula (I) wherein R is hydrogen, hydroxy, C1-C10-alkyl, C1-C10-alkoxy, C1-C4-alkylamino, di-C1-C4-alkylamino, C1-C4-acylamino, COOR1, -CH2-R2, wherein R1 is hydrogen or C1-C4-alkyl or R2-CH 2-and R2 is hydroxy, C1-C4-alkoxy, C1-C4-alkylamino or di-C1-C4-alkylamino, and X is Cl, br or I. The process provides a useful method for preparing compounds that can be used in a variety of applications, including but not limited to agrochemicals.
In one embodiment, the compounds having formula (III) may comprise different combinations of cis-trans isomers, such as 100% trans, or 99% cis and 1% trans, or various cis-trans ratios from about 35:65 to about 99:1. In one embodiment, the compound having formula (III) comprises the trans isomer. In one embodiment, the R group in formula (III) is a C1-C10-alkoxy group. In another embodiment, the R group in formula (III) is C1-alkoxy and both n and m are 1.
Further, the specific structure having formula (III) is represented by formula (IIIS).
In another embodiment, the process may be used to prepare compounds having formula (I) wherein R is C1-C10-alkoxy. In embodiments, the methods provide a convenient method for preparing compounds that are commonly used in a variety of applications, including agrochemicals. Furthermore, the process can be used for preparing compounds of formula (I) wherein R is C1-alkoxy. In an embodiment, the method provides a more specific method for preparing a compound having a specific alkyl group. Furthermore, the process can be used for preparing compounds of formula (I) wherein R is C1-alkoxy, n is 1 and m is 1. The process provides a more specific process for preparing specific compounds having the formula (I) having a specific structure.
Further, the specific structure of the cyclic ketone having the formula (I) IS represented by the formula (IS).
In one embodiment, the process involves preparing a novel intermediate having formula (II) as represented above. In one embodiment, the R group in formula (II) is a C1-C10-alkoxy group. In one embodiment, the R group in formula (II) is a C1-alkoxy group and both n and m are 1. In one embodiment, X is Cl, br or I.
Further, the specific structure of the halogenated imine having the formula (II) is represented by the formula (IIs).
More specifically, the method according to the invention can be illustrated, for example, by the following scheme:
In one embodiment, the oxidizing step is performed in the presence of water. In one embodiment, the oxidizing step is performed at a temperature of about-5 ℃ to about 15 ℃. In one embodiment, the oxidation is performed at a temperature in the range of about-5 ℃ to about 0 ℃.
According to some embodiments, the oxidizing step may be performed at atmospheric pressure.
Furthermore, the oxidation step is carried out in the presence of water. This method provides a convenient method for performing the oxidation step and can be particularly useful when water is readily available.
In one embodiment, the oxidation step may be performed at a temperature in the range of about-5 ℃ to about 15 ℃. In addition, the process may be conducted at a temperature of from about 0 ℃ to about 5 ℃. In exemplary embodiments, salts of hypohalous acids derived from hypochlorous, hypobromous or hypoiodic acid may be used. These acids are commonly used in many chemical reactions, and the process provides a useful method for using these acids in the preparation of compounds having formula (I). In addition, salts of hypohalite such as sodium, potassium, lithium or calcium salts may be used.
In one embodiment, the molar ratio between the compound having formula (III) and the salt of hypohalous acid may be, but is not limited to, about 1:1 to about 1:5. In one embodiment, the molar ratio between the compound having formula (III) and the salt of hypohalous acid is in the range of about 1:2. It can be noted that the hydrolysis step is carried out in the presence of a base. In another embodiment, the base used in the hydrolysis step may be an inorganic base.
In one embodiment, the inorganic base used in the hydrolysis step may be a sulfite or thiosulfate. The sulfite used in the hydrolysis step may be sodium bisulfite, sodium metabisulfite, sodium sulfite, potassium bisulfite, potassium metabisulfite, or potassium sulfite. The thiosulfate used in the hydrolysis step may be sodium thiosulfate or potassium thiosulfate.
According to some embodiments, the hydrolysis step may be performed at atmospheric pressure.
In one embodiment, the addition of the base is performed at a temperature in the range of about-5 ℃ to about 25 ℃.
In one embodiment, the addition of the base is performed at a temperature in the range of about-5 ℃ to about 0 ℃.
In some embodiments, the molar ratio between the compound having formula (II) and the base is from about 1:1 to about 1:5. In one embodiment, the molar ratio between the compound having formula (II) and the base is about 1:2.
In one embodiment, the hydrolysis step is performed in the presence of an acid. The acid may be hydrochloric acid, hydrobromic acid, p-toluenesulfonic acid, sulfuric acid.
In one embodiment, the addition of the acid is performed at a temperature in the range of about-5 ℃ to about 25 ℃.
In one embodiment, the molar ratio between the compound having formula (II) and the acid is from about 10:1 to about 2:1.
In one embodiment, the hydrolysis step is performed in the presence of an organic solvent. The organic solvent may be methanol, acetonitrile, toluene, ethyl acetate, methylene chloride, dichloroethane, xylene, isopropyl acetate or monochlorobenzene.
In one embodiment, the ratio between water and organic solvent is in the range of about 8:2 to about 8:5. In one embodiment, the hydrolysis is performed at a temperature in the range of about 10 ℃ to about 90 ℃. In one embodiment, the hydrolysis is performed at a temperature in the range of about 20 ℃ to about 25 ℃.
In one embodiment, the compound having formula (III) may comprise different combinations of cis-trans isomers. In one embodiment, the R group in formula (III) is a C1-C10-alkoxy group. In another embodiment, the R group in formula (III) is a C1-alkoxy group.
In one embodiment, the compound having formula (I) is prepared in a one-pot process.
The invention also relates to compounds of formula (II)
(II)
Wherein R, X and n are as defined above, m represents the number of R groups and satisfies the relationship 1≤m≤8+2n and at least one R substituent is C1-C4-alkoxy. In some embodiments, n is equal to 1. In some embodiments, R is C1-alkoxy. In some embodiments, m is equal to 1. In some embodiments, n and m are equal to 1 and R is C1-alkoxy.
In some embodiments, the oxidation is performed at a temperature ranging from about-5 ℃ to about 15 ℃. In some embodiments, the oxidation is performed at a temperature ranging from about 0 ℃ to about 5 ℃.
In some embodiments, the salt of hypohalous acid is derived from hypochlorous acid, hypobromous acid, or hypoiodic acid. In some embodiments, the salt of a hypohalite is selected from the sodium, potassium, lithium, or calcium salts.
In some embodiments, the molar ratio between the compound having formula (III) and the salt of hypohalous acid is in the range of about 1:1 to about 1:5. In some embodiments, the molar ratio between the compound having formula (III) and the salt of hypohalous acid is in the range of about 1:2.
The compounds of formula (I) are important intermediates and are used in the preparation of spirotetramat, as described in WO 9805638 A2, which is incorporated herein by reference in its entirety.
In an embodiment of the present invention, a process for preparing spirotetramat comprises the step (a) of preparing a compound having formula (I) as described above. Furthermore, the method comprises the step (b) of providing reaction conditions for preparing spirotetramat.
According to an embodiment, the reaction conditions in step (b) include, but are not limited to, hydantoin formation, hydrolysis of hydantoin, esterification of amino acids, amide formation, cyclization, followed by ethoxycarbonylation to obtain spirotetramat.
In some embodiments, a method for preparing spirotetramat comprises preparing a compound having formula (I) according to the present disclosure.
In some embodiments, spirotetramat is produced according to the methods disclosed herein.
By some embodiments, the spirotetramat is cis-spirotetramat or in the form of a mixture of its cis-trans isomers.
It will be apparent to those skilled in the art that the foregoing examples have been provided for illustrative purposes only without departing from the scope of the present disclosure.
The reaction of trans-cyclic amino acids via haloimines to cyclic ketones can in any case undergo numerous modifications and variations, all of which are covered by the same innovative concept. Furthermore, all the details may be replaced by technically equivalent elements. In practice, the components used, as well as the number, shape and size of the components, may be of any form, depending on the technical requirements. Accordingly, the scope of the invention is defined by the appended claims.
Unless otherwise indicated, all numbers expressing, for example, quantities of ingredients or ratios between ingredients used in the specification are to be understood as being modified in all instances by the term "about". Thus, unless stated to the contrary, the numerical parameters set forth in this specification are approximations that may vary by up to plus or minus 10% depending upon the desired properties to be obtained by the present invention.
The subject matter of the present invention is illustrated by the following examples, which are not to be construed as limiting in any way.
A raw material preparation step of preparing a compound having the formula (IIIS) from cis-trans-8-methoxy-1, 3-diazaspiro [4.5] decane-2, 4-dione.
Example 1:
300 g [1.303 moles ] of cis-trans 8-methoxy-1, 3-diazaspiro [4.5] decane-2, 4-dione (assay: 86%), 122.32 g [2.99 moles ] of sodium hydroxide (assay: 98%) and 1500 ml [5.0 vol ] water were added to a2 liter (L) autoclave at 25℃to 30 ℃. The reaction mixture is heated to a temperature of about 130 ℃ to 135 ℃ for about 12 to 14 hours. The depletion of the reaction mixture cis-trans-8-methoxy-1, 3-diazaspiro [4.5] decane-2, 4-dione was monitored by High Performance Liquid Chromatography (HPLC). After the reaction was completed, the autoclave was cooled to about 25 ℃ to 30 ℃. The reaction mass was unloaded at 20-25 ℃ and charged into a 5.0L four-necked round bottom flask. The pH was adjusted to 5.0-5.5 by using concentrated hydrochloric acid at 25-30℃and stirred for about 30 min. The water was distilled under vacuum at 640-610 mmHg and 75-80 ℃ until a minimum stirrable or 0.5 to 1.0 vol. Water, i.e., 150-300 mL water, remained. The reaction mass was cooled to a temperature of about 20 ℃ to 25 ℃ and 600 mL [2.0 vol ] toluene was added at a temperature of about 20 ℃ to 25 ℃ and stirred for about 30 min. The solid was filtered using a Buckner funnel. The solid was blotted dry at 20-25 ℃ to about 30-60 min. A wet solid product of 432.0 g was obtained with theoretical yield 262.12 g and HPLC purity of 78.61%, corresponding to 164.8% w/w (wet solid yield).
Preparing a compound (4-methoxycyclohexanone) having formula (IS) from a compound (cis: trans 1-amino-4-methoxycyclohexane-1-carboxylic acid) having formula (IIIS) via a compound (N-chloro-4-methoxycyclohexane-1-imine compound) having formula (IIS) without isolation:
example 2:
Two four-necked round bottom flasks, flask a and flask B, equipped with a mechanical stirrer, thermometer, condenser, capacities 0.5L and 1.0L, respectively, were used. 200 mL [4.0 vol ] water, 67.4 g [0.252 moles ] cis-trans-1-amino-4-methoxycyclohexane-1-carboxylic acid were added to flask A at a temperature of about 25-30 ℃ and stirred. Flask B was charged with 395.74 g [2.0 equivalents ] sodium hypochlorite (assay: 9.5%) and cooled to a temperature of about 0-5 ℃. The solution obtained in flask a was added to flask B over a period of 2 hours while maintaining the temperature at about 0-5 ℃, followed by continued stirring at a temperature of about 0-5 ℃ for 30 min. The progress of the reaction was monitored by HPLC, which showed depletion of cis-trans-1-amino-4-methoxycyclohexane-1-carboxylic acid. 100 mL [ 2.0. 2.0 vol ] toluene was added and stirred at a temperature of about 20 ℃ to 25 ℃. The reaction mass was cooled to 0-5 ℃ and 32.47 g [1.0 eq ] sodium sulfite was added over 10-15 min and stirred for another 15 min while maintaining the temperature at about 0-5 ℃. This step was repeated again, after which the temperature of the reaction mass was raised to 20-25 ℃ and maintained at the same temperature for 30-34 hours. The progress of the reaction, i.e. the exhaustion of N-chloro-4-methoxycyclohexane-1-imine, was monitored by GC. The reaction mass was allowed to settle and the aqueous and organic layers were separated at 20-25 ℃. 100 mL [2.0 vol ] of toluene was charged into the aqueous layer of the reaction mass, and after stirring 15 min, toluene and the aqueous layer were separated at 20-25 ℃. The post-processing may be performed several times, if desired. The toluene layer was distilled off under vacuum at 550-580 mm/Hg and 45-50 ℃. The yield of 4-methoxycyclohexanone from cis, trans 8-methoxy-1, 3-diazaspiro [4.5] decane-2, 4-dione was found to be 16.64 g, which had the theoretical yield 32.32 g. The crude weight yield of 4-methoxycyclohexanone from cis-trans-8-methoxy-1, 3-diazaspiro [4.5] decane-2, 4-dione was found to be 59.68%, with a GC purity of 99.1%, an assay of 98.0%, and an assay correction yield of 58.68%.
Characterization details of N-chloro-4-methoxycyclohexane-1-imine are shown in FIGS. 1-9 ,1H NMR (CDCl3, 400 MHz)：3.53 (m, 1H), 3.37 (s, 3H), 2.84 – 2.70 (m, 1H), 2.69- 2.61 (m, 2H), 2.48 -2.41 (m, 1H), 1.98- 1.80 (m, 2H), 1.86-1.78 (m, 2H).
13C NMR (CDCl3, 125 MHz):181.90, 74.58, 56.03, 32.22, 30.28, 29.40, 28.18;
GC purity (% area normalized): 95.93%; GC-MS (M+): 161.
Example 3:
in this case, example 2 was repeated with toluene: water system (water: 4.0 vol, naOCl:2.0 eq, na 2SO3: 2.0 eq, toluene: 2.0 vol) at 20 ℃ to 25 ℃ for 24 hours. The GC area was found to be 99.57% of 4-methoxycyclohexanone and 0.04% of N-chloro-4-methoxycyclohexane-1-imine.
Example 4:
In this case, example 2 was repeated with ethyl acetate:water system (water: 4.0 vol, naOCl:2.0 eq, na 2SO3: 2.0 eq, ethyl acetate: 2.0 vol.) at 20-25 ℃. After 20 hours, 99.1% of 4-methoxycyclohexanone and 0.08% of N-chloro-4-methoxycyclohexane-1-imine were found in GC area.
Preparation of Compound (4-methoxycyclohexanone) having formula (IS) from Compound (N-chloro-4-methoxycyclohexane-1-imine) having formula (IIS):
Example 5:
Preparation of 4-methoxycyclohexanone from N-chloro-4-methoxycyclohexane-1-imine was carried out by taking 2.0 g N-chloro-4-methoxycyclohexane-1-imine and water at 20-25℃4.0 vol..toluene 2.0 vol..na 2S2O3:2.0 equivalents. After 20 hours, 29.12% of the GC area for 4-methoxycyclohexanone and 67.53% of N-chloro-4-methoxycyclohexane-1-imine were found, after 30 hours, 34.41% of the GC area for 4-methoxycyclohexanone and 62.17% of N-chloro-4-methoxycyclohexane-1-imine were found, and after 48 hours, 48.26% of the GC area for 4-methoxycyclohexanone and 48.24% of N-chloro-4-methoxycyclohexane-1-imine were found.
Example 8:
In this case, 4-methoxycyclohexanone was prepared from N-chloro-4-methoxycyclohex-1-imine by taking 3.0 g of N-chloro-4-methoxycyclohex-1-imine and water 4.0 vol, 1.5 equivalents of aqueous HCl at a temperature of about 0-5C, after 4 hours, 54.34% of 4-methoxycyclohexanone, 20.79% of N-chloro-4-methoxycyclohexane-1-imine and 18.68% of the GC area of the impurity 2-chloro-4-methoxycyclohexane-1-one were found.
Example 9:
In this case, 4-methoxycyclohexanone is prepared from N-chloro-4-methoxycyclohex-1-imine by taking 3.0 g N-chloro-4-methoxycyclohex-1-imine and water 4.0 vol, H 2SO4: 1.5 equivalent for 30min at a temperature of about 0-5 ℃ and then for 1 hour at 20-25 ℃. It was found that 43.00% of 4-methoxycyclohexanone and 29.59% of N-chloro-4-methoxycyclohexane-1-imine and 16.69% of impurity 2-chloro-4-methoxycyclohexane-1-one were GC area.
Cis-trans 8-methoxy-1, 3-diazaspiro [4.5] decane-2, 4-dione from compound (4-methoxycyclohexanone) having formula (IS):
Example 10:
Preparation of cis-trans-8-methoxy-1, 3-diazaspiro [4.5] decane-2, 4-dione from 4-methoxycyclohexanone was carried out by taking 100 g equivalents of 4-methoxycyclohexanone, 1.5 equivalents of ammonium carbonate, 1.1 equivalents of sodium cyanide and 5.0 vol. Water and reacting it at 50-55℃for 6 hours. Cis-trans 8-methoxy-1, 3-diazaspiro [4.5] decane-2, 4-dione was isolated at a cis-trans ratio 76.79:23.13.

Claims (43)

1.本发明还涉及一种用于制备具有式 (II) 的化合物的方法1. The present invention also relates to a method for preparing a compound having formula (II). (II)(II) 其中R是氢、羟基、C1-C10-烷基、C1-C10-烷氧基、C1-C4-烷基氨基、二-C1-C4-烷基氨基、C1-C4-酰氨基、COOR1、-CH2-R2，其中R1是氢或C1-C4-烷基或R2-CH2-并且R2是羟基、C1-C4-烷氧基、C1-C4-烷基氨基或二-C1-C4-烷基氨基；X是Cl、Br或I；n表示碳原子的数目并且是0、1、2的任何整数；并且m表示R基团的数目并且满足以下关系式：0 ≤ m ≤ 8 + 2n；Where R is hydrogen, hydroxyl, C1-C10-alkyl, C1-C10-alkoxy, C1-C4-alkylamino, di-C1-C4-alkylamino, C1-C4-amide, COOR1, -CH2-R2, where R1 is hydrogen or C1-C4-alkyl or R2-CH2- and R2 is hydroxyl, C1-C4-alkoxy, C1-C4-alkylamino or di-C1-C4-alkylamino; X is Cl, Br or I; n represents the number of carbon atoms and is any integer of 0, 1, or 2; and m represents the number of R groups and satisfies the following relationship: 0 ≤ m ≤ 8 + 2n; 所述方法包括：The method includes: 用次卤酸的盐氧化具有式 (III) 的化合物Oxidation of compounds having formula (III) by salts of hypohalic acids (III)(III) 其中R、n和m是如上所定义的，并且至少一个R取代基是C1-C4-烷氧基。Wherein R, n and m are as defined above, and at least one R substituent is a C1-C4-alkoxy group. 2.一种用于制备具有式 (I) 的化合物的方法2. A method for preparing a compound having formula (I). 其中R是氢、羟基、C1-C10-烷基、C1-C10-烷氧基、C1-C4-烷基氨基、二-C1-C4-烷基氨基、C1-C4-酰氨基、COOR1、-CH2-R2，其中R1是氢或C1-C4-烷基或R2-CH2-并且R2是羟基、C1-C4-烷氧基、C1-C4-烷基氨基或二-C1-C4-烷基氨基；n表示碳原子的数目并且是0、1、2的任何整数；并且m表示R基团的数目并且满足以下关系式：0 ≤ m ≤ 8 + 2n；Where R is hydrogen, hydroxyl, C1-C10-alkyl, C1-C10-alkoxy, C1-C4-alkylamino, di-C1-C4-alkylamino, C1-C4-amide, COOR1, -CH2-R2, where R1 is hydrogen or C1-C4-alkyl or R2-CH2- and R2 is hydroxyl, C1-C4-alkoxy, C1-C4-alkylamino or di-C1-C4-alkylamino; n represents the number of carbon atoms and is any integer of 0, 1, or 2; and m represents the number of R groups and satisfies the following relationship: 0 ≤ m ≤ 8 + 2n; 所述方法包括：The method includes: (a) 用次卤酸的盐氧化具有式 (III) 的化合物(a) Oxidation of compounds having formula (III) by salts of hypohalic acids ——其中R是如上所定义的，以得到具有式 (II) 的化合物—where R is as defined above, to obtain a compound having formula (II). (II)(II) 其中R、n和m是如上所定义的，并且X是Cl、Br或I；以及Where R, n, and m are as defined above, and X is Cl, Br, or I; and (b) 在水的存在下水解所述具有式 (II) 的化合物。(b) Hydrolyzing the compound having formula (II) in the presence of water. 3.根据权利要求1所述的方法，其中，所述具有式 (III) 的化合物包含反式异构体。3. The method according to claim 1, wherein the compound having formula (III) comprises a trans isomer. 4.根据权利要求1或2所述的方法，其中，R是C1-C10-烷氧基。4. The method according to claim 1 or 2, wherein R is a C1-C10-alkoxy group. 5.根据权利要求1-3中任一项所述的方法，其中，R是C1-烷氧基。5. The method according to any one of claims 1-3, wherein R is a C1-alkoxy group. 6.根据权利要求1-4中任一项所述的方法，其中，R是C1-烷氧基，n是1并且m是1。6. The method according to any one of claims 1-4, wherein R is C1-alkoxy, n is 1 and m is 1. 7.根据权利要求1-5中任一项所述的方法，其中，所述氧化在水的存在下在约-5°C至约15°C的温度范围下进行。7. The method according to any one of claims 1-5, wherein the oxidation is carried out in the presence of water at a temperature range of about -5°C to about 15°C. 8.根据权利要求6所述的方法，其中，所述氧化在水的存在下在约-5°C至约0°C的温度范围下进行。8. The method of claim 6, wherein the oxidation is carried out in the presence of water at a temperature range of about -5°C to about 0°C. 9.根据权利要求1-7中任一项所述的方法，其中，所述次卤酸的盐衍生自次氯酸、次溴酸或次碘酸。9. The method according to any one of claims 1-7, wherein the salt of the hypohalic acid is derived from hypochlorous acid, hypobromic acid, or hypoiodic acid. 10.根据权利要求1-8中任一项所述的方法，其中，所述次卤酸的盐选自钠盐、钾盐、锂盐或钙盐。10. The method according to any one of claims 1-8, wherein the salt of the hypohalic acid is selected from sodium salt, potassium salt, lithium salt or calcium salt. 11.根据权利要求1-9中任一项所述的方法，其中，具有式 (III) 的化合物与所述次卤酸的盐之间的摩尔比在约1 : 1至约1 : 5的范围内。11. The method according to any one of claims 1-9, wherein the molar ratio between the compound having formula (III) and the salt of the hypohalic acid is in the range of about 1:1 to about 1:5. 12.根据权利要求10所述的方法，其中，具有式 (III) 的化合物与所述次卤酸的盐之间的摩尔比在约1 : 2的范围内。12. The method according to claim 10, wherein the molar ratio between the compound having formula (III) and the salt of the hypohalic acid is in the range of about 1:2. 13.根据权利要求1-11中任一项所述的方法，其中，所述水解在碱的存在下进行。13. The method according to any one of claims 1-11, wherein the hydrolysis is carried out in the presence of an alkali. 14.根据权利要求12所述的方法，其中，所述碱是无机碱。14. The method according to claim 12, wherein the base is an inorganic base. 15.根据权利要求13所述的方法，其中，所述无机碱选自亚硫酸盐或硫代硫酸盐。15. The method according to claim 13, wherein the inorganic base is selected from sulfites or thiosulfates. 16.根据权利要求14所述的方法，其中，所述亚硫酸盐选自亚硫酸氢钠、焦亚硫酸钠、亚硫酸钠、亚硫酸氢钾、焦亚硫酸钾或亚硫酸钾。16. The method according to claim 14, wherein the sulfite is selected from sodium bisulfite, sodium metabisulfite, sodium sulfite, potassium bisulfite, potassium metabisulfite, or potassium sulfite. 17.根据权利要求14所述的方法，其中，所述硫代硫酸盐选自硫代硫酸钠或硫代硫酸钾。17. The method according to claim 14, wherein the thiosulfate is selected from sodium thiosulfate or potassium thiosulfate. 18.根据权利要求1-16中任一项所述的方法，其中，所述碱的添加在约-5°C至约25°C的温度范围下进行。18. The method according to any one of claims 1-16, wherein the addition of the alkali is carried out in a temperature range of about -5°C to about 25°C. 19.根据权利要求17所述的方法，其中，所述碱的添加在约-5°C至约0°C的温度范围下进行。19. The method of claim 17, wherein the addition of the alkali is carried out in a temperature range of about -5°C to about 0°C. 20.根据权利要求1-18中任一项所述的方法，其中，具有式 (II) 的化合物与所述碱之间的摩尔比在约1 : 1至约1 : 5的范围内。20. The method according to any one of claims 1-18, wherein the molar ratio between the compound having formula (II) and the base is in the range of about 1:1 to about 1:5. 21.根据权利要求19所述的方法，其中，具有式 (II) 的化合物与所述碱之间的摩尔比在约1 : 2的范围内。21. The method according to claim 19, wherein the molar ratio between the compound having formula (II) and the base is in the range of about 1:2. 22.根据权利要求1-11中任一项所述的方法，其中，所述水解在酸的存在下进行。22. The method according to any one of claims 1-11, wherein the hydrolysis is carried out in the presence of an acid. 23.根据权利要求21所述的方法，其中，所述酸选自盐酸、氢溴酸、对甲苯磺酸、硫酸。23. The method according to claim 21, wherein the acid is selected from hydrochloric acid, hydrobromic acid, p-toluenesulfonic acid, and sulfuric acid. 24.根据权利要求21或22所述的方法，其中，所述酸的添加在约-5°C至约25°C的温度范围下进行。24. The method according to claim 21 or 22, wherein the addition of the acid is carried out in a temperature range of about -5°C to about 25°C. 25.根据权利要求1-11、21-23中任一项所述的方法，其中，具有式 (II) 的化合物与所述酸之间的摩尔比在约10 : 1至约2 : 1的范围内。25. The method according to any one of claims 1-11, 21-23, wherein the molar ratio between the compound having formula (II) and the acid is in the range of about 10:1 to about 2:1. 26.根据权利要求1-24中任一项所述的方法，其中，所述水解在有机溶剂的存在下进行。26. The method according to any one of claims 1-24, wherein the hydrolysis is carried out in the presence of an organic solvent. 27.根据权利要求25所述的方法，其中，所述有机溶剂选自甲醇、乙腈、甲苯、乙酸乙酯、二氯甲烷、二氯乙烷、二甲苯、乙酸异丙酯或一氯苯。27. The method according to claim 25, wherein the organic solvent is selected from methanol, acetonitrile, toluene, ethyl acetate, dichloromethane, dichloroethane, xylene, isopropyl acetate, or monochlorobenzene. 28.根据权利要求25或26所述的方法，其中，所述水与所述有机溶剂之间的比率在约8: 2至约8 : 5的范围内。28. The method according to claim 25 or 26, wherein the ratio between the water and the organic solvent is in the range of about 8:2 to about 8:5. 29.根据权利要求1-27中任一项所述的方法，其中，所述水解在约10°C至约90°C的温度范围下进行。29. The method according to any one of claims 1-27, wherein the hydrolysis is carried out in a temperature range of about 10°C to about 90°C. 30.根据权利要求28所述的方法，其中，所述水解在约20°C至约25°C的温度范围下进行。30. The method of claim 28, wherein the hydrolysis is carried out in a temperature range of about 20°C to about 25°C. 31.根据权利要求1-29中任一项所述的方法，其中，所述具有式 (I) 的化合物以一锅法制备。31. The method according to any one of claims 1-29, wherein the compound having formula (I) is prepared by a one-pot method. 32.一种具有式 (II) 的化合物32. A compound having formula (II) (II)(II) 其中R、X和n是如上所定义的，m表示R基团的数目并且满足以下关系式：1 ≤ m ≤ 8 +2n并且至少一个R取代基是C1-C4-烷氧基。Where R, X and n are as defined above, m represents the number of R groups and satisfies the following relationship: 1 ≤ m ≤ 8 + 2n and at least one R substituent is C1-C4-alkoxy. 33.根据权利要求31所述的化合物，其中，n等于1。33. The compound according to claim 31, wherein n equals 1. 34.根据权利要求31或32所述的化合物，其中，R是C1-烷氧基。34. The compound according to claim 31 or 32, wherein R is a C1-alkoxy group. 35.一种用于制备具有式 (II) 的化合物的方法35. A method for preparing a compound having formula (II). (II)(II) 所述方法包括：The method includes: 用次卤酸的盐氧化所述具有式 (III) 的化合物The compound having formula (III) is oxidized by a salt of hypohalic acid. (III)(III) 其中R、X和n是如上所定义的，m表示R基团的数目并且满足以下关系式：1 ≤ m ≤ 8 +2n并且至少一个R取代基是C1-C4-烷氧基。Where R, X and n are as defined above, m represents the number of R groups and satisfies the following relationship: 1 ≤ m ≤ 8 + 2n and at least one R substituent is C1-C4-alkoxy. 36.根据权利要求34所述的方法，其中，所述氧化在约-5°C至约15°C的温度范围下进行。36. The method of claim 34, wherein the oxidation is carried out in a temperature range of about -5°C to about 15°C. 37.根据权利要求35所述的方法，其中，所述氧化在约0°C至约5°C的温度范围下进行。37. The method of claim 35, wherein the oxidation is carried out at a temperature range of about 0°C to about 5°C. 38.根据权利要求35或36所述的方法，其中，所述次卤酸的盐衍生自次氯酸、次溴酸或次碘酸。38. The method according to claim 35 or 36, wherein the salt of the hypohalic acid is derived from hypochlorous acid, hypobromic acid, or hypoiodic acid. 39.根据权利要求34-37中任一项所述的方法，其中，所述次卤酸的盐选自钠盐、钾盐、锂盐或钙盐。39. The method according to any one of claims 34-37, wherein the salt of the hypohalic acid is selected from sodium salt, potassium salt, lithium salt or calcium salt. 40.根据权利要求34-38中任一项所述的方法，其中，具有式 (III) 的化合物与所述次卤酸的盐之间的摩尔比在约1 : 1至约1 : 5的范围内。40. The method according to any one of claims 34-38, wherein the molar ratio between the compound having formula (III) and the salt of the hypohalic acid is in the range of about 1:1 to about 1:5. 41.根据权利要求39所述的方法，其中，具有式 (III) 的化合物与所述次卤酸的盐之间的摩尔比在约1 : 2的范围内。41. The method according to claim 39, wherein the molar ratio between the compound having formula (III) and the salt of the hypohalic acid is in the range of about 1:2. 42.一种用于制备螺虫乙酯的方法，所述方法包括：42. A method for preparing spirotetramat, the method comprising: 根据权利要求1-40中任一项所述的方法制备具有式 (I) 的化合物。Compounds having formula (I) are prepared by the method according to any one of claims 1-40. 43.一种螺虫乙酯，其根据权利要求41所述的方法生产。43. A spirotetramat produced according to the method of claim 41.
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