TW387876B - A process for preparing 2-(substituted benzoyl)-1,3-cyclohexanedione compounds of formula (I) - Google Patents

Description

A7 -------------- B7 _ V. Description of the invention (1) The present invention relates to the preparation of 2- (substituted benzyl alcohol) _ 丨, 3 cyclohexanedione compounds . 2-(Substituted benzyl) _, 3-cyclohexanedione is known as a herbicide 'from, for example, U.S. Patent No. 4,780,127, U.S. Patent No. 4,806,146, U.S. Patent No. 4,946,981, U.S. Patent No. 5 No. 06158, WO 9408988 and WO 94 < M524. One way to prepare these compounds is by rearrangement of the acetol esters. This method is disclosed in U.S. Patent No. 4,780,127 and U.S. Patent No. 4,695,673. It is necessary in the presence of hydrogen cyanide or cyanide anion in such rearrangement reactions (usually in an amount of 1 to 10 molar ratio, equivalent to marginal alcohol esters). It is desirable to avoid the use of these substances in industrial scale processes. Surprisingly it was found that in some solvents it can be rearranged in the absence of hydrogen cyanide or the anion anion. Printed by Shellfish Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs

According to the present invention, there is provided a method for preparing a compound of formula (I), wherein R1, R2, R3, R4, r5 * r6 are independently hydrogen or ci 6 alkyl; r7 is halogen, cyano, NO], (^ -4 alkane) Alkyl; ¢ ^ .4 alkoxy or RaS where Ra is (^ bu azepto); r8, r9 and Rio are independently hydrogen, halogen, Cm alkoxy, Cw alkoxy, Cw haloalkyl, Cw Haloalkoxy, CN, No2, phenoxy or substituted phenoxy; Rbs (0) n 0m where m is 0 or 1, η is 0, 1 or 2 and Rb is C 1-4 alkyl, C haloalkyl, phenyl or benzyl, NHCORc where 1 ^ is (: 1-4 alkyl 'NRdRe where Rd and Re are independently hydrogen or c 丨 _4 alkyl; RfC (O)-where Rf is hydrogen, Ci_4 alkyl, Cb4 haloalkyl, or Cl4 alkoxy; So2NRgRh, where Rg and Rh are each independently hydrogen or Ci_4 tiger; or any two of R8, R9, and R10 together with the carbon atom to which they are attached form a group containing Up to three selected from 0, N or S -4-This paper size applies the Chinese Standard (CNS) Congji (21GX297 mm) 印 Printed by the Employee Consumer Cooperative of the Central Government Bureau of the Ministry of Economic Affairs Α7 Β7 V. Description of the invention (2) a 5 or 6 member heterocyclic ring of a hetero atom, and optionally Substituted by (3 ^ 4 alkyl, c 1-4 haloalkyl, oxy, = NOC alkyl or halogen; this method includes compounds of formula (II) where R1, R2, R3, r4, r5, R6, R7, R8, R9 and R10. As defined in formula (I), the rearrangement in the detection and polar aprotic solvents is characterized in that the method is performed on a medium without ammonia hydrogen or cyanide anions The term " alkyl " as used herein refers to a straight or branched chain. The term " southern group " refers to an alkyl group substituted with at least one southern element. Similarly, the term " from alkoxy " Refers to an alkoxy group substituted with at least one southern element. The term "halogen" as used herein refers to fluorine, gas, bromine, and iodine. Phenoxy R8, R9, and R1 (> suitable optional substituents R Examples include halogens such as fluorine and chlorine and c1-4 haloalkyl. Preferred compounds of formula (I) are those wherein R1, R2, R3, R4, R5, and R6 are independently hydrogen or CU6 pit group; R7 is halogen , Cyano, NO ,, C, or 1-4 alkyl; Cw haloalkyl, Cw alkoxy, or RaS where Ra is Cw alkyl; R8, R9, and Rio are independently hydrogen, halogen, (^ _4alkyl) , C ^ _4 pit oxygen C1-4_alkyl, Ci-4 halohaloxy, CN, No2, phenoxy or substituted phenoxy; RbS (〇) n Om where m is 0 or 1, and n is 0, 1 or 2 and Rb are 0; Bu 4 alkyl, Ci-4 haloalkyl, phenyl or benzyl, NHCORc where Rc is Cw alkyl 'NRdRe where Rd and Re are independently hydrogen or Cl_4 alkyl; RFC (O)- Where Rf is hydrogen, Cl_4 alkyl, (^ _4 southern alkyl, or Cl-4 alkoxy; or SC ^ NRgRh where Rg and Rh are independently hydrogen or Cl_4 alkyl. Preferably R1, R2, R3, R4, R5 * R6 are independently hydrogen or 4-alkyl. More preferably, R1, R2, ruler 5 and ruler 6 are hydrogen, and ruler 3 and ruler 4 are independently hydrogen or methyl. -5- This paper XJL is applicable to Chinese National Standard (CNS) Α4ίΙ (210X297 mm) C Please read the precautions on the back before filling out this page} --- Ί: ---: --- ------一 laJ-I _ m _--· Printed by A7 B7 of the Consumer Cooperatives of the Central Sample Bureau of the Ministry of Economics (R7 is preferably halogen or No. R8 is preferably valuable and R is hydrogen. R 9 is preferably hydrogen Or Cl · * alkoxy, especially ethoxy. Optimal r9 is hydrogen 0, preferably R 10 is Rb S (0) n0m where Rb, η and m are as defined above. More preferably m is zero , Η is 2 and Rb is CH3 or C2H5. The best R10 is the group attached to the 4-position CH3SO2 of the benzyl group. Suitable bases include organic bases such as trialkylamine and inorganic bases such as alkali metal carbonates and phosphoric acid. Both salts. The trialkylamine is preferably a tri (lower alkyl) amine with i to 6 ', preferably 1 to 4 carbon atoms per alkyl group. A particularly preferred amine is triethylamine. A suitable inorganic The base includes sodium carbonate, potassium carbonate, and trisodium tribasic acid. When used in combination with a dipolar aprotic solvent such as dimethylformamide, even bicarbonates such as potassium bicarbonate will be effective in this reaction. Preferred bases Sodium acid and potassium carbonate. Alkali is used at about 1 to about 4 moles per mole enol ester, preferably 2 moles per mole enol ester. Used herein " is substantially free of hydrogen cyanide or cyanide The word anion, means that these moieties have not been added to the reaction medium. Preferred solvents for using this method are acetonitrile, dimethylformamide, tetrahydrofuran, and these solvents with non-polar solvents such as toluene or xylene. In general, depending on the nature of the reactants and the source of cyanide, the rearrangement can be carried out at a temperature of 0 ° C, up to about 100 ° C. The preferred temperature is about 80 ° C maximum. Best The temperature is about 20 ° C to about 70 ° C. In some cases, such as possible problems when an excessive by-product is formed (for example, when using o-nitrobenzyl halide) Should be kept at about 4 〇 maximum -6 This paper size applies Chinese National Standard (CNS) A4 specification (21〇297mm) {Please read the precautions on the back before filling this page)

387876

5. Description of the invention (i. This method can use the enol ester as the starting material, or carry out in situ the enol ester produced, for example, a compound of formula (111) where r1, r2, r3, chi 4, R5 and R6 is defined in the related formula (i) and r7, R8, and R% R1 in the compound of formula (iv). It is the definition of the related formula (i) and z is a southern element, preferably the reverse of the gas. When the enol ester is taken as As the starting material, it can be prepared by any of a number of known methods, including the tritiated action of a compound of formula (III) and a compound of formula (IV). Printed by the Consumer Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs · 1-! · ' , I — 1--II: II (please read the legal notices on the back before filling this page) According to the preparation of the compound of formula (I) according to the present invention, it is advantageous to start with the compounds of formula (111) and (IV) With and without isolation of the intermediate product enol ester (2). When carried out in two steps, the compound of formula (II) and the compound of formula (IV) are reacted in the presence of test or alkaline earth carbonate. From The enol ester obtained from the resulting product mixture is isolated by known techniques, such as by acid The resulting solution is washed with sodium chloride solution and dried. This technique is advantageous when different ashing agents are preferred for the first step-rearrangement of the dilute alcohol to the compound of formula (I). For example, acetonitrile, 2-dioxane, or toluene is mixed with an appropriate ning agent and contacted with an appropriate amount of a source of cyanide, a phase transfer catalyst, in the presence of sodium carbonate and water, and heated to a temperature to produce The final product. Alternatively, 'the vinegar can be retained, retained in the reaction product and if necessary to produce a compound of formula (I), the second stage can be performed by adding another base (using the same solvent). Comparable production can be obtained with or without isolation of the enol ester. The compound of formula (I) can be obtained from the reaction in its salt form. The required formula (I)

.I -I 1 II-I -7- This paper is suitable for t 囷 home rubbing standard (CNS) A4 size (2 丨 0X297 mm) 387876 A7 B7__ 5. Description of the invention (5) The tritiated compound can be acidified and treated with Obtained by appropriate solvent extraction. The method of the present invention is illustrated by the following examples. Example 1 Acetonitrile (25 g) was fed into a 250 ml 4-necked round-bottomed flask which was flame-dried first with N2 and sealed into a Drierite protective tube and an oil bubbler. Feed 1,3-cyclohexanedione (5.0 g) and sodium carbonate powder (12.0 g) to produce a red mud slurry. The mass was heated to 55-57 ° C and fixed for 20 minutes. Gasified 2-Ga-4- (methylsulfonyl) benzylhydrazine (11.0 g) was added to acetonitrile (25 g) and gradually heated to obtain a complete solution. This solution was added dropwise to the block at 5 5-5 7 ° C, and passed a hot dropping funnel for 20 minutes to produce a pale yellow mud. The agglomerates are held at 55-57 ° C for 17 hours. The desired compound of formula (I) as a sodium salt was prepared in 82% yield. Example 2 In the second example, acetonitrile was replaced by dimethylamidamine and sodium carbonate was replaced by an equal amount of potassium carbonate. Following the same procedure, the reaction yielded 54% of the desired compound of formula (I) in a complete and bell salt form 20 minutes after the termination of the base gas addition. Example 3 The procedure of Example 1 was repeated, and triethylamine was used in place of sodium carbonate and DMF to replace acetonitrile *. After 4 hours of reaction, the yield was 45%. ____ _ 8 _ I Paper Approved Household Standards (CNS) (Training Director) 387876 V. Description of Invention (6) A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Chemical Formula (in the manual)

8 R

ο, (, ° (Please read the notes on the back before filling out this page) —Order. -Good, -9- This paper size applies to China National Standard (CNS) A4 (210X297 mm) /

Claims (1)

387876 No. 8510 Chinese Patent Application No. 0966 (Patent Reparation) A8 Sep. 88) gg Amendment 丨-Detective 1 VI, Application 1 ¾ Example 8 ^. -IffJ Tti 1. A Preparation Formula (I) of 2- (Substituted benzamidine) -1,3-cyclohexanone compound method: R 'corpse: .〇 / 〇_ {! R3' J0 • Rs (I) -------- install— (Please read the precautions on the back before filling this page) The Central Standards Bureau of the Ministry of Economic Affairs, Shellfish Consumer Cooperative, printed that R1, R2, R5 and R6 are hydrogen R3 and R4 are hydrogen or methyl respectively; R7 is halogen, N02, alkyl, (3 ^ 4 halogen); and R8, R9, and R10 are independently hydrogen, halogen, Ci_4 alkyl, alkoxy, C i_4 haloalkyl or RbS (0) n0m, where m is 0 or 1, η is 0, 1 or 2, and Rb is Cb4 alkyl or (: b 4 haloalkyl; the method includes a compound of formula (II) Rearrangement reaction This paper uses the Chinese National Standard (CNS) A4 specification (210X297 mm) 387876 No. 8510 Chinese Application No. 0966 Patent Application (Patent Reparation A8 September 1988) gg Amendment 1¾ 范 8 ^. -IffJ Tti 1. A method for preparing 2- (substituted benzamyl) -1,3-cyclohexanone compound of formula (I): R 'corpse: .〇 / 〇_ {! R3 ' J0 • Rs (I) -------- install— (Please read the precautions on the back before filling this page) The Central Standards Bureau of the Ministry of Economic Affairs, Shellfish Consumer Cooperative, printed that R1, R2, R5 and R6 are hydrogen R3 and R4 are hydrogen or methyl respectively; R7 is halogen, N02, alkyl, (3 ^ 4 halogen); and R8, R9, and R10 are independently hydrogen, halogen, Ci_4 alkyl, alkoxy, C i_4 haloalkyl or RbS (0) n0m, where m is 0 or 1, η is 0, 1 or 2, and Rb is Cb4 alkyl or (: b 4 haloalkyl; the method includes a compound of formula (II) Rearrangement reaction This paper uses China National Standards (CNS) A4 specifications (210X297 mm) ό 387876 AS Β8 C8 D8 R7, R8, R9, and Rl0 are selected from the scope of patent applications for triethylamine and carbonic acid, among which Rl, R2, R3, R4 , R5, r6 are as defined in formula (I), which is based on the test of sodium or carbonic acid-selected from acetonitrile, dimethyl formamidine '= four', or these solvents with toluene or xylene It is performed in the presence of a polar aprotic agent, and is characterized in that the method is performed in a reaction medium that is substantially free of cyanide anions. Hydrogen cyanide or 2. The method according to item 1 of the scope of patent application, wherein R7 is Nansu or 3. The method according to item 1 of the scope of patent application, wherein R8 is gas. 4. Method according to item i of the scope of patent application, = oxy. Where R is hydrogen or Cy 垸 5, according to the patent application Fanyuan! Method, in which r 1〇 is connected to the 4th position of the benzylidene group (: 113502 bases. (Please read the note on the back before filling in this page). Printed by the Industrial and Consumer Cooperatives, this paper is scaled up and out of use (CNS) Α4 size (210 × 297 mm)