Synthesis of cyclic ketones from cyclic amino acids

Abstract

A process for the preparation of a compound of formula (I) wherein R is hydrogen, hydroxyl, 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-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, 2; and m represents the number of R groups and satisfies the following relational expression: 0 < = m < = 8 + 2n. The present invention relates to a process for the preparation of a compound of formula (I), comprising: (a) oxidizing a compound of formula (III) with a salt of a hypohalous acid, where R is as defined above, to obtain a compound of formula (II), where R, n and m are as defined above, and X is Cl, Br or I; and (b) hydrolyzing the compound of formula (II) in the presence of water.

Description

Technical Field

[0001] The present invention generally relates to a method for preparing cyclic ketones, and more particularly to a novel route for synthesizing 4-methoxycyclohexanone from cyclic amino acids, and more particularly 1-amino-4-methoxycyclohexane-1-carboxylic acid. Background Technology

[0002] The use of cyclic ketones as starting materials in the synthesis of insecticides, acaricides, and herbicides is well-known. They are particularly important in the synthesis of cyclic ketone enol insecticides, and especially in the synthesis of spirotetramat.

[0003] Cyclic amino acids can typically be obtained via Bucherer-Bergs synthesis or Strecker synthesis, each yielding different isomer forms. The conditions for using Bucherer-Bergs synthesis in the preparation of substituted cyclic amino acids having the general formula (1) are described below.

[0004]

[0005] The cis isomer (1-a) is mainly obtained, while the conditions of the Streck synthesis mainly yield the trans isomer (1-b).

[0006] Where R 1 OR 2 R 2 Indicates alkyl

[0007]

[0008] The Buchner-Borgs reaction is typically carried out by reacting a substituted cyclic ketone with the general formula (2):

[0009]

[0010] Where R 1 It is as defined above.

[0011] Hydantoin having the general formula (3) is subsequently separated in a solvent or solvent mixture of ammonium carbonate and alkali metal cyanide:

[0012]

[0013] Hydantoin is obtained as a mixture of the following cis isomers (3a) and trans isomers (3b):

[0014]

[0015] This method can be illustrated, for example, by the following scheme:

[0016]

[0017] Among them, R 1 OR 2 And R 2 Indicates alkyl group.

[0018] The cis:trans mixture can be separated with ammonia, as defined in (US 7148377 B2).

[0019] In addition, physical separation methods, such as column chromatography or fractional crystallization, can be used to separate mixtures of cis:trans spirocyclic isomers, and cis spirocyclic isomers can be separated, as disclosed in US 7897803 B2.

[0020] Furthermore, in WO 2002 / 02532 and US 8710238 B2, a mixture of cis:trans hydantoin isomers is treated with ammonia, and because the solubility of the cis salt is significantly lower than that of the trans salt, cis hydantoin can be separated with high purity by filtration, while the trans hydantoin remains in the solution.

[0021] In addition, US 8710238 B2 discloses the separation of the cis isomer when a mixture of cis:trans hydantoin isomers is stirred together with an aqueous solution of an alkali metal hydroxide or an alkaline earth metal hydroxide.

[0022] However, existing techniques for producing cis-hydantoin from cyclic ketones simultaneously produce the undesirable trans-hydantoin. This results in unsatisfactory yields. Furthermore, none of these existing techniques utilize a cis:trans mixture of hydantoin compounds to produce cyclic ketones.

[0023] Therefore, there is a need to develop a method for producing cyclic ketones from cis:trans hydantoin.

[0024] Purpose of the invention

[0025] The object of this invention is to provide a method for synthesizing cyclic ketones from cyclic amino acids via intermediate haloimine using oxidation followed by hydrolysis.

[0026] The object of this invention is to provide a method for preparing compounds having formula (I):

[0027]

[0028] 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.

[0029] The object of this invention is to provide a compound having formula (II):

[0030]

[0031] Where R, n, and m are as defined above, and X is Cl, Br, or I. Summary of the Invention

[0032] According to one aspect, embodiments of the present invention disclose a method for preparing a compound having formula (I).

[0033]

[0034] 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;

[0035] The method includes:

[0036] (a) Oxidation of compounds having formula (III) by salts of hypohalous acids

[0037]

[0038] —where R is as defined above, to obtain a compound having formula (II).

[0039]

[0040] Where R, n, and m are as defined above, and X is Cl, Br, or I; and

[0041] (b) Hydrolyzing the compound having formula (II) in the presence of water.

[0042] In one embodiment, the compound having formula (III) comprises a trans isomer.

[0043] In another embodiment, the compound having formula (III) comprises 99% cis isomer and 1% trans isomer.

[0044] In another embodiment, the compound having formula (III) comprises 1% cis isomer and 99% trans isomer.

[0045] In another embodiment, the compound having formula (III) comprises various ratios of cis:trans, for example about 35:65 to about 99:1.

[0046] According to another aspect, embodiments of the present invention disclose a compound having formula (II).

[0047]

[0048] 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 a C1-C4-alkoxy group.

[0049] According to another aspect, embodiments of the present invention disclose a method for preparing a compound having formula (II).

[0050]

[0051] The method includes:

[0052] (a) Oxidation of compounds having formula (III) by salts of hypohalous acids

[0053]

[0054] 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 a C1-C4-alkoxy group. Attached Figure Description

[0055] The accompanying drawings illustrate various embodiments of the system, method, and other aspects of this disclosure. Those skilled in the art will understand that the element boundaries (e.g., boxes, groups of boxes, or other shapes) shown in the drawings represent one instance of a boundary. It is possible that in some instances, one element may be designed as multiple elements, or multiple elements may be designed as one element. In some instances, 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. A non-limiting and non-exhaustive description is described with reference to the following drawings. The components in the drawings are not necessarily drawn to scale, but are intended to illustrate principles.

[0056] Figure 1 The N-chloro-4-methoxycyclohexane-1-imine according to the examples is shown. 1 H NMR spectrum.

[0057] Figure 2 The N-chloro-4-methoxycyclohexane-1-imine according to the examples is shown. 13 C NMR spectrum.

[0058] Figure 3 and Figure 4 Gas chromatography (GC) of N-chloro-4-methoxycyclohexane-1-imine according to an example is shown.

[0059] Figures 5-9 The gas chromatography-mass spectra of N-chloro-4-methoxycyclohexane-1-imine according to an example are shown. Detailed Implementation

[0060] Some embodiments of this disclosure, showcasing all its features, will now be discussed in detail. The terms “comprising,” “having,” “containing,” and “including,” and other forms thereof, are intended to be semantically equivalent and are open-ended, as one or more items following any of these terms do not imply an exhaustive list of such one or more items, or imply limitation 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” and “the” include plural references unless the context clearly indicates otherwise. While any systems and methods similar to or equivalent to those described herein may be used in the practice or testing of embodiments of this disclosure, preferred systems and methods are described hereafter.

[0061] Embodiments of this disclosure will be described more fully below with reference to the accompanying drawings, in which the same reference numerals denote the same elements throughout the drawings, and exemplary embodiments are illustrated. However, the embodiments of the claims may be implemented 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 among other possible examples.

[0062] This invention relates to a method for preparing compounds having formula (I).

[0063]

[0064] The method comprises two steps: oxidation of a compound having formula (III) with a salt of hypohalic acid.

[0065]

[0066] To obtain compounds having formula (II)

[0067]

[0068] The compound having formula (II) was then hydrolyzed in the presence of water.

[0069] The method according to the invention can be described, for example, through the following scheme:

[0070]

[0071] In one embodiment, the method can be used to prepare various compounds having formula (I), wherein R is hydrogen, hydroxyl, C1-C10-alkyl, C1-C10-alkoxy, C1-C4-alkylamino, di-C1-C4-alkylamino, C1-C4-amide, COOR1, -CH2-R2, wherein 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, and X is Cl, Br or I. This method provides a useful approach for preparing compounds that can be used in a variety of applications, including but not limited to agrochemicals.

[0072] In one embodiment, a compound 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 of about 35:65 to about 99:1. In one embodiment, a compound having formula (III) comprises a 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 a C1-alkoxy group and both n and m are 1.

[0073] Furthermore, a specific structure having equation (III) is represented by equation (IIIS).

[0074]

[0075] In another embodiment, the method can be used to prepare compounds having formula (I), wherein R is a C1-C10-alkoxy group. In the embodiments, the method provides a convenient method for preparing compounds commonly used in various applications, including agrochemicals. Furthermore, the method can be used to prepare compounds having formula (I), wherein R is a C1-alkoxy group. In the embodiments, the method provides a more specific method for preparing compounds having a specific alkyl group. Furthermore, the method can be used to prepare compounds having formula (I), wherein R is a C1-alkoxy group, n is 1, and m is 1. The method provides a more specific method for preparing specific compounds having formula (I) with a specific structure.

[0076] Furthermore, the specific structure of the cyclic ketone having formula (I) is represented by formula (IS).

[0077]

[0078] In one embodiment, the method involves preparing a novel intermediate having formula (II) as shown 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.

[0079] Furthermore, the specific structure of the haloimine having formula (II) is represented by formula (IIS).

[0080]

[0081] More specifically, the method according to the invention can be described, for example, through the following scheme:

[0082]

[0083] In one embodiment, the oxidation step is carried out in the presence of water. In one embodiment, the oxidation step is carried out at a temperature of about -5°C to about 15°C. In one embodiment, the oxidation is carried out in a temperature range of about -5°C to about 0°C.

[0084] According to some embodiments, the oxidation step can be carried out at atmospheric pressure.

[0085] Furthermore, the oxidation step is carried out in the presence of water. This method provides a convenient way to perform the oxidation step and can be particularly useful when water is readily available.

[0086] In one embodiment, the oxidation step can be carried out at a temperature range of about -5°C to about 15°C. Alternatively, the method can be carried out at a temperature of about 0°C to about 5°C. In an exemplary embodiment, salts of hypohalous acids derived from hypochlorous acid, hypobromoic acid, or hypoiodic acid can be used. These acids are commonly used in many chemical reactions, and this method provides a useful approach for using these acids in the preparation of compounds having formula (I). Furthermore, salts of hypohalous acids, such as sodium, potassium, lithium, or calcium salts, can be used.

[0087] In one embodiment, the molar ratio between the compound having formula (III) and the salt of the hypohalous acid can 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 the 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 can be an inorganic base.

[0088] In one embodiment, the inorganic base used in the hydrolysis step can be a sulfite or a thiosulfate. The sulfite used in the hydrolysis step can be sodium bisulfite, sodium metabisulfite, sodium sulfite, potassium bisulfite, potassium metabisulfite, or potassium sulfite. The thiosulfate used in the hydrolysis step can be sodium thiosulfate or potassium thiosulfate.

[0089] According to some embodiments, the hydrolysis step can be carried out at atmospheric pressure.

[0090] In one embodiment, the addition of the alkali is carried out at a temperature range of about -5°C to about 25°C.

[0091] In one embodiment, the addition of the alkali is carried out at a temperature range of about -5°C to about 0°C.

[0092] In some embodiments, the molar ratio between the compound having formula (II) and the base is 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.

[0093] In one embodiment, the hydrolysis step is carried out in the presence of an acid. The acid may be hydrochloric acid, hydrobromic acid, p-toluenesulfonic acid, or sulfuric acid.

[0094] In one embodiment, the acid is added at a temperature range of about -5°C to about 25°C.

[0095] In one embodiment, the molar ratio between the compound having formula (II) and the acid is about 10:1 to about 2:1.

[0096] In one embodiment, the hydrolysis step is carried out in the presence of an organic solvent. The organic solvent may be methanol, acetonitrile, toluene, ethyl acetate, dichloromethane, dichloroethane, xylene, isopropyl acetate, or monochlorobenzene.

[0097] In one embodiment, the ratio of water to organic solvent is in the range of about 8:2 to about 8:5. In one embodiment, hydrolysis is carried out at a temperature range of about 10°C to about 90°C. In one embodiment, hydrolysis is carried out at a temperature range of about 20°C to about 25°C.

[0098] In one embodiment, a 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.

[0099] In one embodiment, the compound having formula (I) is prepared by a one-pot method.

[0100] The present invention also relates to compounds having formula (II).

[0101]

[0102] (II)

[0103] 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 a C1-C4-alkoxy group. In some embodiments, n equals 1. In some embodiments, R is a C1-alkoxy group. In some embodiments, m equals 1. In some embodiments, n and m equal 1 and R is a C1-alkoxy group.

[0104] In some embodiments, oxidation is carried out at a temperature range of about -5°C to about 15°C. In some embodiments, oxidation is carried out at a temperature range of about 0°C to about 5°C.

[0105] In some embodiments, the salts of hypohalic acids are derived from hypochlorous acid, hypobromoic acid, or hypoiodic acid. In some embodiments, the salts of hypohalic acids are selected from sodium, potassium, lithium, or calcium salts.

[0106] In some embodiments, the molar ratio between the compound having formula (III) and the salt of the 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 the hypohalous acid is in the range of about 1:2.

[0107] Compounds having 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.

[0108] In embodiments of the present invention, a method for preparing spirotetramat includes step (a): preparing a compound having formula (I) as described above. Furthermore, the method includes step (b): providing reaction conditions for the preparation of spirotetramat.

[0109] According to the examples, the reaction conditions in step (b) include, but are not limited to, hydantoin formation, hydantoin hydrolysis, amino acid esterification, amide formation, cyclization, followed by ethoxycarbonylation to obtain spirotetramat.

[0110] In some embodiments, a method for preparing spirotetramat includes preparing a compound having formula (I) according to this disclosure.

[0111] In some embodiments, spirotetramat is produced according to the methods disclosed herein.

[0112] In some embodiments, spirotetramat is in the form of cis-spirotetramat or a mixture of its cis:trans isomers.

[0113] It will be apparent to those skilled in the art that the above examples are provided for illustrative purposes only without departing from the scope of this disclosure.

[0114] The reaction of cis:trans cyclic amino acids via haloimins to cyclic ketones can undergo numerous modifications and variations in any case, all of which are encompassed by the same innovative concept. Furthermore, all details can be replaced by technically equivalent elements. In practice, the components used, as well as the quantity, shape, and size of the components, can be of any form, depending on the technical requirements. Therefore, the scope of protection of this invention is defined by the appended claims.

[0115] Unless otherwise stated, all figures used in this specification that represent, for example, the number of components or the ratio between components, should be understood to be modified by the term "about" in all cases. Therefore, unless stated to the contrary, the numerical parameters presented in this specification are approximate values ​​and can vary by up to plus or minus 10% according to the desired properties to be obtained according to the invention.

[0116] The subject matter of this invention is illustrated by the following examples, but is not intended to be limited in any way.

[0117] The raw material preparation step involves preparing a compound having formula (IIIS) from cis:trans-8-methoxy-1,3-diazaspiro[4.5]decane-2,4-dione.

[0118] Example 1:

[0119]

[0120] Add 300 g [1.303 mol] of cis:trans-8-methoxy-1,3-diazaspiro[4.5]decane-2,4-dione (as determined: 86%), 122.32 g [2.99 mol] of sodium hydroxide (as determined: 98%), and 1500 ml [5.0 vol.] of water to a 2 L autoclave at 25°C–30°C. Heat the reaction mixture to approximately 130°C–135°C and maintain this temperature for approximately 12–14 hours. Monitor the depletion of the cis:trans-8-methoxy-1,3-diazaspiro[4.5]decane-2,4-dione reaction mixture by high-performance liquid chromatography (HPLC). After the reaction is complete, cool the autoclave to approximately 25°C–30°C. Unload the reaction mixture at 20°C–25°C and transfer it to a 5.0 L four-necked round-bottom flask. Adjust the pH to 5.0–5.5 at 25°C–30°C using concentrated hydrochloric acid and stir for approximately 30 min. Distill the water under vacuum at 640–610 mmHg and 75°C–80°C until a minimum stirable volume of 0.5–1.0 vol. (150–300 mL) of water remains. Cool the reaction mixture to approximately 20°C–25°C and add 600 mL of [2.0 vol.] toluene at approximately 20°C–25°C, stirring for approximately 30 min. Filter the solid using a Buckner funnel. Blot the solid dry at 20°C–25°C for approximately 30–60 min. 432.0 g of wet solid product is obtained, with a theoretical yield of 262.12 g and an HPLC purity of 78.61%, corresponding to 164.8% w / w (wet solids yield).

[0121] A compound having the formula (IIIS) (4-methoxycyclohexanone) is prepared from a compound having the formula (IIIS) (cis:trans-1-amino-4-methoxycyclohexane-1-carboxylic acid) via a compound having the formula (IIS) (N-chloro-4-methoxycyclohexane-1-imine compound):

[0122] Example 2:

[0123]

[0124] Two four-necked round-bottom flasks, A and B, equipped with mechanical stirrers, thermometers, condensers, and capacities of 0.5 L and 1.0 L respectively, were used. 200 mL [4.0 vol.] of water and 67.4 g [0.252 mol] of cis:trans-1-amino-4-methoxycyclohexane-1-carboxylic acid were added to flask A at approximately 25°C–30°C and stirred. 395.74 g [2.0 equivalent] of sodium hypochlorite (as determined: 9.5%) was added to flask B and cooled to approximately 0°C–5°C. The solution obtained in flask A was added to flask B over a 2-hour period while maintaining the temperature at approximately 0°C–5°C, followed by stirring at approximately 0°C–5°C for another 30 min. The progress of the reaction was monitored by HPLC, which showed depletion of cis:trans-1-amino-4-methoxycyclohexane-1-carboxylic acid. Add 100 mL [2.0 vol.] toluene at approximately 20°C–25°C and stir. Cool the reaction mixture to 0°C–5°C and add 32.47 g [1.0 equivalent] sodium sulfite over 10–15 min, stirring for another 15 min while maintaining the temperature at approximately 0°C–5°C. Repeat this step again, then raise the temperature of the reaction mixture to 20°C–25°C and maintain the same temperature for 30–34 hours. Monitor the reaction progress by GC until the depletion of N-chloro-4-methoxycyclohexane-1-imine. Allow the reaction mixture to settle and separate the aqueous and organic layers at 20°C–25°C. Add 100 mL [2.0 vol.] toluene to the aqueous layer of the reaction mixture and, after stirring for 15 min, separate the toluene and aqueous layers at 20°C–25°C. Several post-treatments may be performed if necessary. The toluene layer was distilled off under vacuum at 550–580 mm / Hg and 45°C–50°C. A 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, with a theoretical yield of 32.32 g. A 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% (98.0% determined) and a corrected yield of 58.68%.

[0125] Characterization details of N-chloro-4-methoxycyclohexane-1-imine, such as Figures 1-9 As shown, 1H NMR (CDCl3, 400MHz): 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).

[0126] 13 C NMR (CDCl3, 125 MHz): 181.90, 74.58, 56.03, 32.22, 30.28, 29.40,28.18;

[0127] GC purity (% area normalized): 95.93%; GC-MS (M+): 161.

[0128] Example 3:

[0129] In this case, Example 2 was repeated for 24 hours at 20°C–25°C using a toluene:water system (water: 4.0 vol., NaOCl: 2.0 equivalent, Na2SO3: 2.0 equivalent, toluene: 2.0 vol.). GC area of ​​99.57% 4-methoxycyclohexanone and 0.04% N-chloro-4-methoxycyclohexane-1-imine was found.

[0130] Example 4:

[0131] In this case, Example 2 was repeated at 20°C–25°C using an ethyl acetate:water system (water: 4.0 vol., NaOCl: 2.0 equivalent, Na₂SO₃: 2.0 equivalent, ethyl acetate: 2.0 vol.). After 20 hours, GC areas of 99.1% 4-methoxycyclohexanone and 0.08% N-chloro-4-methoxycyclohexane-1-imine were observed.

[0132] Compound (4-methoxycyclohexanone) with formula (IS) was prepared from a compound (N-chloro-4-methoxycyclohexane-1-imine) having formula (IIS):

[0133] Example 5:

[0134]

[0135] The preparation of 4-methoxycyclohexanone from N-chloro-4-methoxycyclohexane-1-imine was carried out as follows: 2.0 g of N-chloro-4-methoxycyclohexane-1-imine and water (4.0 vol.), toluene (2.0 vol.), and Na₂S₂O₃ (2.0 equivalent) were taken at 20°C–25°C. After 20 hours, a GC area of ​​29.12% 4-methoxycyclohexanone and 67.53% N-chloro-4-methoxycyclohexane-1-imine was found; after 30 hours, a GC area of ​​34.41% 4-methoxycyclohexanone and 62.17% N-chloro-4-methoxycyclohexane-1-imine was found; and after 48 hours, a GC area of ​​48.26% 4-methoxycyclohexanone and 48.24% N-chloro-4-methoxycyclohexane-1-imine was found.

[0136] Example 8:

[0137]

[0138] In this case, the preparation of 4-methoxycyclohexanone from N-chloro-4-methoxycyclohexane-1-imine was carried out as follows: 3.0 g of N-chloro-4-methoxycyclohexane-1-imine and water: 4.0 vol., aqueous HCl solution: 1.5 equivalents were taken at a temperature of about 0°C-5°C; after 4 hours, the GC area of ​​54.34% 4-methoxycyclohexanone, 20.79% N-chloro-4-methoxycyclohexane-1-imine and 18.68% impurity 2-chloro-4-methoxycyclohexane-1-one was found.

[0139] Example 9:

[0140] In this case, the preparation of 4-methoxycyclohexanone from N-chloro-4-methoxycyclohexane-1-imine was carried out as follows: 3.0 g of N-chloro-4-methoxycyclohexane-1-imine and water: 4.0 vol., H2SO4: 1.5 equivalents were taken and heated at a temperature of about 0°C–5°C for 30 min, followed by heating at 20°C–25°C for 1 hour. The GC area was found to be 43.00% 4-methoxycyclohexanone, 29.59% N-chloro-4-methoxycyclohexane-1-imine, and 16.69% impurity 2-chloro-4-methoxycyclohexane-1-one.

[0141] Cis:trans-8-methoxy-1,3-diazaspiro[4.5]decane-2,4-dione from a compound having the formula (IS) (4-methoxycyclohexanone):

[0142] Example 10:

[0143]

[0144] The 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 of 4-methoxycyclohexanone, 1.5 equivalents of ammonium carbonate, 1.1 equivalents of sodium cyanide, and 5.0 vol. of water and reacting at 50°C–55°C for 6 hours. The cis:trans-8-methoxy-1,3-diazaspiro[4.5]decane-2,4-dione was separated at a cis:trans ratio of 76.79:23.13.

Claims

1. The present invention also relates to a method for preparing compounds having formula (II). (II) 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; The method includes: Oxidation of compounds having formula (III) by salts of hypohalic acids (III) Wherein R, n and m are as defined above, and at least one R substituent is a C1-C4-alkoxy group.

2. A method for preparing a compound having formula (I). 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; The method includes: (a) Oxidation of compounds having formula (III) by salts of hypohalous acids —where R is as defined above, to obtain a compound having formula (II). (II) Where 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.

3. The method according to claim 1, wherein, The compound having formula (III) contains a trans isomer.

4. The method according to claim 1 or 2, wherein, R is a C1-C10-alkoxy group.

5. The method according to any one of claims 1-3, wherein, R is a C1-alkoxy group.

6. The method according to any one of claims 1-4, wherein, R is a C1-alkoxy group, n is 1 and m is 1.

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. The method according to 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. The method according to any one of claims 1-7, wherein, The salts of the hypohaloic acid are derived from hypochlorous acid, hypobromoic acid, or hypoiodic acid.

10. The method according to any one of claims 1-8, wherein, The salt of the hypohalic acid is selected from sodium, potassium, lithium, or calcium salts.

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. 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. The method according to any one of claims 1-11, wherein, The hydrolysis is carried out in the presence of an alkali.

14. The method according to claim 12, wherein, The base is an inorganic base.

15. The method according to claim 13, wherein, The inorganic base is selected from sulfites or thiosulfates.

16. The method of claim 14, wherein, The sulfite is selected from sodium bisulfite, sodium metabisulfite, sodium sulfite, potassium bisulfite, potassium metabisulfite, or potassium sulfite.

17. The method of claim 14, wherein, The thiosulfate is selected from sodium thiosulfate or potassium thiosulfate.

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. 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. 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. 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. The method according to any one of claims 1-11, wherein, The hydrolysis is carried out in the presence of acid.

23. The method according to claim 21, wherein, The acid is selected from hydrochloric acid, hydrobromic acid, p-toluenesulfonic acid, and sulfuric acid.

24. The method according to claim 21 or 22, wherein, The acid is added at a temperature range of about -5°C to about 25°C.

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. The method according to any one of claims 1-24, wherein, The hydrolysis is carried out in the presence of an organic solvent.

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. The method according to claim 25 or 26, wherein, The ratio of water to organic solvent is in the range of about 8:2 to about 8:

5.

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. The method according to claim 28, wherein, The hydrolysis is carried out at a temperature range of about 20°C to about 25°C.

31. The method according to any one of claims 1-29, wherein, The compound having formula (I) was prepared by a one-pot method.

32. A compound having formula (II) (II) 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. The compound according to claim 31, wherein, n equals 1.

34. The compound according to claim 31 or 32, wherein, R is a C1-alkoxy group.

35. A method for preparing a compound having formula (II). (II) The method includes: The compound having formula (III) is oxidized by a salt of hypohalic acid. (III) 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. The method according to claim 34, wherein, The oxidation is carried out in a temperature range of about -5°C to about 15°C.

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. The method according to claim 35 or 36, wherein, The salts of the hypohaloic acid are derived from hypochlorous acid, hypobromoic acid, or hypoiodic acid.

39. The method according to any one of claims 34-37, wherein, The salt of the hypohalic acid is selected from sodium, potassium, lithium, or calcium salts.

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. 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. A method for preparing spirotetramat, the method comprising: The method according to any one of claims 1-40 is used to prepare a compound having formula (I).

43. A spirotetramat produced according to the method of claim 41.

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