WO2010055042A1

WO2010055042A1 - 2-[(1-cyanopropyl)carbamoyl]-5-methoxymethyl nicotinic acids and the use thereof in manufacturing herbicidal imidazolinones

Info

Publication number: WO2010055042A1
Application number: PCT/EP2009/064950
Authority: WO
Inventors: David Cortes
Original assignee: Basf Se
Priority date: 2008-11-13
Filing date: 2009-11-11
Publication date: 2010-05-20
Also published as: AR074329A1; TW201021702A; UY32242A

Abstract

2-[(1 -cyanopropyl)carbamoyl]-5-methoxymethyl nicotinic acids of formula (I) where Z is hydrogen or halogen; Z¹ is hydrogen, halogen, cyano or nitro; R¹ is C₁C₄ alkyl; R₂ is C₁C₄ alkyl, C₃-C₆ cycloalkyl or R¹ and R², when taken together with the atom to which they are attached, represent a C₃-C₆ cycloalkyl group optionally substituted with methyl, and R³ is hydrogen or a cation preferably selected from the group consisting of alkali metals, alkaline earth metals, manganese, copper, iron, zinc, cobalt, lead, silver, nickel, ammonium and organic ammonium; are useful intermediates for the synthesis of herbicidal imidazolinones.

Description

2-[(1 -cyanopropyl)carbamoyl]-5-methoxymethyl nicotinic acids and the use thereof in manufacturing herbicidal imidazolinones

Description

The invention relates to 2-[(1-cyanopropyl)carbamoyl]-5-methoxymethyl nicotinic acids, the preparation of these compounds and their use in manufacturing herbicidal imidazolinones, such as imazamox.

Derivatives of 2-(2-imidazolin-2-yl) nicotinic acids, like imazamox (2-[(RS)-4-isopropyl-4- methyl-5-oxo-2-imidazolin-2-yl]-5-methoxymethyl nicotinic acid),

are useful selective herbicides which act as ALS-inhibitors and can be used in pre- and post-emergence applications.

Various processes for the synthesis of these compounds are known from the literature, see e.g. EP-A 0 322 616, EP-A 0 747 360, EP-A 0 933 362 or Q. Bi et al, Modern Agrochemi- cals 6(2)(2007) 10-14.

Although synthesis on an industrial scale is carried out by these methods there is still room for improvement, specifically in view of economical and ecological aspects, such as overall yield improvement or the avoidance of certain solvents or reagents.

EP-A 0 322 616 discloses the synthesis of 2-[(1-carbamoyl-1 ,2-dimethylpropyl)carbamoyl]- 5-chloromethyl nicotinic acid by reaction of 5-chloromethyl-2,3-pyridine dicarboxylic acid anhydride with α-amino-α-methylvaleramide and further conversion of this compound to imazamox by reaction with NaOCH₃ and subsequent acidification.

One task of the invention is to provide new useful intermediates for the synthesis of herbicidal imidazolinones, and a process for their preparation. A further task of the invention is to provide an improved process for manufacturing herbicidal imidazolinones, like imazamox. It has been found that 2-[(1-cyanopropyl)carbamoyl]-5-methoxymethyl nicotinic acids are useful intermediates in the manufacture of herbicidal imidazolinones.

EP-A 0184027 and EP-A 0142718 describe the reaction of pyridine-2,3-dicarboxylic acid anhydrides with 2-amino-2,3-dimethyl-butyronitrile and further conversion to herbicidal imidazolinones, however, no examples for 5-methoxymethyl substituted compounds are disclosed.

Accordingly, in one aspect of the invention there is provided a 2-[(1- cyanopropyl)carbamoyl]-5-methoxymethyl nicotinic acid of formula (I),

where

Z is hydrogen or halogen; Z¹ is hydrogen, halogen, cyano or nitro; R¹ is CrC₄ alkyl; R² is CrC₄ alkyl, C₃-C₆ cycloalkyl or R¹ and R², when taken together with the atom to which they are attached, represent a C₃-C₆ cycloalkyl group optionally substituted with methyl, and

R³ is hydrogen or a cation preferably selected from the group consisting of alkali metals, alkaline earth metals, manganese, copper, iron, zinc, cobalt, lead, silver, nickel, ammonium and organic ammonium.

In another aspect of the invention there is provided a process for preparing a 2-[(1- cyanopropyl)carbamoyl]-5-chloromethyl nicotinic acid of formula (I), comprising the step of

(i) reacting a 5-methoxymethyl-pyridine-2,3-dicarboxylic acid anhydride of formula (H).

where Z, Z¹ are as in formula (I), with a 2-aminoalkane carbonitrile (III), H₂N-CR¹R²-CN (III) where R¹ and R² are as in formula (I).

In a further aspect of the invention there is provided the use of a compound of formula (I) for preparing a herbicidal imidazolinone of formula (IV),

wherein

Z, Z¹, R¹, R², R³ are as defined in formula (I).

In a further aspect of the invention there is provided a process for preparing a herbicidal imidazolinone compound of formula (IV),

comprising the steps of:

(i) hydrolyzing the nitrile of formula (I) to obtain an amide of formula (V),

where

Z, Z¹, R¹, R², R³ are as defined in formula (I); and

(ii) reacting compound (V) with MOH/CH₃OH (where M is alkali metal, preferably

Na or K), optionally followed by acidification to form the herbicidal imidazolinone (IV).

The use of the novel intermediate (I) in the synthesis of herbicidal imidazolinones leads to an improved yield in preparing amide (V) and, thus, in the overall yield of the synthetic process. The regioselectivity of the opening of the anhydride is excellent even without the addition of the nitrogen bases recommended in EP-A 0 144 595. Surprisingly, the meth- oxymethyl group is stable in the further synthesis of the herbicidal imidazolinones.

In formula (I) the symbols preferably have the following meanings:

Z is preferably hydrogen. Z¹ is preferably hydrogen. R¹ is preferably CrC₄ alkyl. R² is preferably Ci-C₄ alkyl. R³ is preferably hydrogen, alkali metal or NR⁴R⁵ ₃, where R⁴ is hydrogen or R⁵, and

R⁵ is CrC₄ alkyl; more preferred hydrogen.

Preferred are compounds of formula (I) where all symbols have the preferred meanings.

A particularly preferred compound of formula (I) is compound (Ia):

and salts thereof.

Compound (I) can be prepared by reaction of anhydride (II) with aminonitrile (III) as exemplified by the synthesis of preferred compound (Ia), where R¹ and R² are defined as in formula (III):

(Ha) (Ilia)

Aminonitriles (III) are commercially available or can be prepared by methods known in the art (see e.g. EP-A 0 095 105). Generally 0.8 to 1.2 equivalents aminonitrile (III) per equivalent of compound (II) are used, preferably 0.95 to 1.1.

The reaction is carried out in a solvent, which is preferably selected from aromatic hydrocarbons, preferably toluene, mesitylenes, chlorinated aromatic hydrocarbons, such as chlorobenzene, dichlorobenzenes, chlorinated aliphatic hydrocarbons, such as 1 ,2- dichloroethane and dichloromethane, acetic acid, and mixtures thereof.

If acetic acid is not used as the main solvent, addition of 0.5 to 10 equivalents, preferably 1 to 3 equivalents (based on compound (II)), is advantageous.

Further advantageous additives that improve the selectivity of the ring-opening reaction (2 versus 3 position) are listed in US 4,562,257, and comprise pyridine, 4-picoline, 2-picoline and quinoline. However, although these additives can be used, according to the invention it is not necessary to employ such additives, and in one embodiment, the listed additives are not present in the reaction mixture. The reaction is generally carried out at a temperature range of from about 40 to about 120⁰C, preferably of from about 60 to about 100⁰C. The reaction time is generally from about 1 to about 3 h.

In a preferred embodiment compound (II) is dissolved in the solvent and brought to the reaction temperature, and aminonitrile (III) is gradually added. After completion of the reaction and cooling, nitrile compound (I) can be isolated by standard methods.

In a further preferred embodiment, however, compound (I) is not isolated but the reaction mixture is directly used for the following hydrolysis of the nitrile.

In a preferred embodiment of the invention the anhydride (II) that is used in the preparation of compound (I) is obtained by a process comprising the steps of

(i) reacting a compound of formula (Vl),

where

Z is H or halogen; Z¹ is H, halogen, CN or NO₂,

with a dehydrating agent in the presence of a base.

The dehydrating agent is preferably acetic anhydride.

The molar ratio of diacid (Vl) to acetic anhydride is generally 1.0 to 1.05.

The synthesis of diacid (Vl) is disclosed, e.g., in EP-A 0 747 360.

In a preferred embodiment, diacid (Vl) is prepared by

(i) reacting a compound of formula (VII)

where

Q is a tertiary aliphatic or cyclic, saturated, partially unsaturated or aromatic amine;

Z is H or halogen;

Z¹ is H, halogen, CN or NO₂;

Y¹ and Y² are each independently OR⁴, NR⁴R⁵, or, when taken together, Y¹Y² is -O-,

-S- or -N R⁶-; R⁴ and R⁵ are each independently H;

CrC₄ alkyl optionally substituted with d-C₄ alkoxy or phenyl optionally substituted with one to three CrC₄ alkyl groups, CrC₄ alkoxy groups or halogen atoms; or phenyl optionally substituted with one to three CrC₄ alkyl groups, CrC₄ alkoxy groups or halogen atoms;

R⁶ is H or CrC₄ alkyl,

in a methanol/H₂O mixture, comprising at least 20% by weight H₂O (based on the sum of water and bromide (VII)), with a base comprising MOCH₃ and/or MOH, where M is alkali metal or alkaline earth metal, under pressure in a closed vessel at a temperature of from about 75 to 110⁰C.

Compound (VII) can be prepared, e.g. as disclosed in EP-A 0 548 532.

The reaction is carried out in a solvent mixture comprising methanol and at least 20 % by weight of water (based on the sum of water and bromide (II)). Preferably the amount of water is from about 25 to about 75%, more preferably 30 to 70%, in particular from about 40 to about 50%. The remainder of the solvent mixture is methanol and up to about 50%, preferably up to about 20% of further solvents, preferably selected from toluene, chloro- benzene and ethanol.

The weight ratio of methanol to bromide (II) is generally in the range of from 0.5-25:1 , preferably 1-20:1 , more preferred 1-10:1 , in particular 2-3:1. The base comprises MeOM, MOH or a mixture of MeOM and MOH where M is alkali metal or alkaline earth metal, preferably Na or K, in particular Na. In cases of mixtures MeOM/MOH M can be the same or different, preferably it is the same.

If MeOM is present, the molar ratio of MeOM, preferably MeONa, to bromide (VII) is generally in the range of 1-10:1 , preferably 1-7.5:1 , more preferably 1.25-7:1 , in particular 1.25- 2:1.

If MOH is present, the molar ratio of MOH, preferably NaOH, to bromide (VII) is generally in the range of 0.5-10:1 , preferably 1-7:1 , more preferably 3-5:1 . If a mixture of MeOM and

MOH is used as base the molar ratio of MOH to bromide (VII) is generally in the range of

0.5-7.5:1 , preferably 1-5:1 , more preferably 3-5:1. In one preferred embodiment no MOH is added to the reaction mixture. For economical reasons it is advantageous to use an excess of MOH with respect to MeOM. In another preferred embodiment, only MOH is used in a ratio of 3-10, more preferred 4-7, more preferred 4.5-6.

The molar ratio of total base added/bromide (VII) is generally from about 2.5-10:1 , preferably from about 3-7:1 , particularly preferred from about 4.5-6:1 . MeOM is typically added dissolved in methanol. MOH is typically added dissolved in water.

The reaction is carried out at a temperature in the range of from about 75 to 110⁰C, preferably in the range of from about 80 to 105⁰C, more preferably in the range of from about 80 to 100°C.

The reaction is carried out in a closed vessel, e.g. in a Parr pressure reactor, at an elevated pressure which is generally in the range of from about 1.01 to 5.00 bar, preferably of from about 1.02 to 4.00 bar, in particular of from about 1.03 to 3.50 bar. In a preferred embodiment no external pressure is applied, and the reaction is carried out at the pressure building up from the solvents at the reaction temperature in the closed vessel.

The reaction time is generally in the range of from about 5 to 20 h, preferably in the range of from about 6 to 9 h, in particular about 8 h.

In a preferred embodiment bromide (VII), containing from about 25 to 75 % by weightwater (based on the sum of water and bromide (VII)), is taken up in methanol, aqueous NaOH is slowly added at a temperature in the range of from about 25 to 40⁰C, followed by NaOCH₃ in methanol which is slowly added at a temperature in the range of from about 40 to 50⁰C. The reaction mixture is then heated to the reaction temperature (typically 80 to 100°C) in a pressure reactor, which is closed, whereupon pressure builds up as the reaction temperature is reached.

After completion of the reaction the mixture is cooled down and can be worked up accord- ing to known procedures, e.g. by cooling, treatment with an acid, such as sulfuric acid, until compound (Vl) precipitates and can be filtered off.

Compound (Vl) prepared as described above is particularly useful for the synthesis of the inventive intermediate (I) because of its purity. Therefore, in a preferred embodiment the process for preparing compound (I) comprises the steps of

(i-1 ) reacting a compound of formula (VII),

where

Z is H or halogen; Z¹ is H, halogen, CN or NO₂;

Y¹ and Y² are each independently OR¹, NR¹R², or, when taken together, Y¹Y² is -O-, -S- or -NR³-;

R¹ and R² are each independently H;

C₁-C₄ alkyl optionally substituted with C₁-C₄ alkoxy or phenyl optionally substi- tuted with one to three C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups or halogen atoms; or phenyl optionally substituted with one to three CrC₄ alkyl groups, CrC₄ alkoxy groups or halogen atoms;

R³ is H or Ci-C₄ alkyl,

in a methanol/H₂O mixture, comprising at least 20% by weight H₂O (based on the sum of water and bromide (VII)), with a base comprising MOCH₃ and/or MOH, where M is alkali metal or alkaline earth metal, under pressure in a closed vessel at a temperature of from about 75 to 110⁰C; (i-2) reacting compound (Vl) formed in step (i-1 ) with a dehydrating agent in the presence of a base, and a solvent selected from methyl tert. -butyl ether, diiso- propylether, cyclopentyl methyl ether, and mixtures thereof, to obtain anhydride (II), and

(i-3) reacting anhydride (II) with a 2-aminoalkane carbonitrile (III),

H₂N-CR¹R²-CN (III), where R¹ and R² are as in formula (I).

The compounds of formula (I) are useful intermediates in the synthesis of herbicidal imida- zolinones (IV).

In a first step the nitrile function is hydrolyzed to yield the respective amide (V) as exempli- fied with preferred compounds (Ia) and (Va):

In a typical procedure 0.8 to 1.2 equivalents (based on (I)) of a strong mineral acid, pref- erably sulfuric acid (preferably in a concentration of 30 to 98%) and water (e.g. 2 to 10 equivalents) are added at a temperature which is generally in the range of about 30⁰C to 120⁰C, preferably 50⁰C to 90⁰C. The mixture is further stirred until complete conversion. The reaction time is generally from 1 to 8 h, preferably 1 to 5 h.

Workup and isolation can be achieved by standard methods, such as precipitation from an aqueous solution (e.g. as its ammonium salt). In a preferred embodiment the reaction mixture is directly used in the following reaction step.

In a further process of the invention a herbicidal imidazolinone compound (IV) is prepared by a process comprising the steps of (i) preparing an amido compound of formula (V); and (ϋ) reacting compound (V) with CH₃OM or MOH/CH₃OH (where M is alkali metal, preferably Na or K) followed by acidification to form the herbicidal imidazolinone

(IV).

In a further preferred embodiment, in step (ii) the reaction mixture from step (i) is reacted with methanol (generally 2 to 100 equivalents based on (V)) in the presence of an aqueous base (generally 3 to 100 equivalents based on (V)), the base being preferably selected from MOH, where M is an alkali metal, preferably Na or K, particularly Na.

The reaction is carried out at a temperature in the range of from 20 to 120⁰C, preferably 40 to 90⁰C. The reaction can be carried out at atmospheric pressure or at elevated pressure, preferably the pressure forming at the desired reaction temperature. The reaction time is generally from 1 to 8 h, preferably from 1 to 5 h.

Isolation of imidazolinone product (IV) can be achieved by standard methods. In a preferred embodiment water is added and organic solvents are distilled off. The residue can be taken up in water and acidified, whereupon compound (IV) precipitates. After filtration the crude product can be further purified, e.g. by stirring with water or re-crystallization.

In a further embodiment of the invention there is provided a process for preparing herbicidal imidazolinones of formula (IV) comprising the step of

(i) reacting compound (I) with a base selected from MOH and MOCH₃, where M is alkali metal, and (aqueous) H₂O₂ in methanol, optionally followed by acidification.

The reaction may be carried out in analogy to the procedures described in EP-A 0 144 595.

The invention is illustrated by the following examples without limiting it thereby. Examples

Example 1

Synthesis of 2-[(1-cyano-1 ,2-dimethylpropyl)carbamoyl]-5-methoxymethyl nicotinic acid (Ia)

a) Synthesis of 5-methoxymethyl-pyridine-2,3-dicarboxylic acid anhydride (Na)

1937 g toluene, 7.3 g (0.08 mol) picoline and 412 g (4.03 mol) acetic anhydride were charged to a reactor. 833 g (3.95 mol) 5-methoxymethyl-pyridine-2,3-dicarboxylic acid (Via) were added and the reaction mixture was heated to 40-60⁰C for 2 h. After completion of the reaction the mixture was used without isolation of the product in the following condensation step. Yield: 99% (determined by HPLC assay)

b) Synthesis of (la)-sodium salt

3215 g of the reaction mixture from step (a) containing 755.80 g (3.91 mol) (Na) were charged to a reactor and kept at 15 to 20⁰C. 584 g (4,14 mol) 2-amino-2,3-dimethyl- butyronitrile in 5400 g toluene were added with cooling and the mixture was maintained at 15 to 20⁰C for additional 30 minutes for complete conversion.

The mixture was used without further isolation of the product (Ia) for hydrolysis and further conversion to imazamox (IVa)

Yield: 89% (determined by HPLC assay), isomer ratio (2:3 adduct) 11 :1.

Example 2

Synthesis of imazamox (IVa)

(a) Synthesis of 2-[(1-carbamoyl-1 ,2-dimethylpropyl)carbamoyl]-5-methoxymethyl nicotinic acid (Va)

9199 g of the reaction mixture from example 1 containing 1074.66 g (3.52 mol) (Ia) was treated with 278 g (15.5 mol) H₂O and, subsequently, 346 g (3.45 mol) sulfuric acid (98%) at a rate to allow for a temperature rise to 50 to 60⁰C. After stirring for 2 h at 50 to 60⁰C 3138 g of water were added, followed by 1 185 g (14.8 mol) 50% aqueous NaOH to adjust the pH-value to 5.5. The resulting mixture contained the hydrolysis product (Va).

After settling the lower aqueous product layer containing (Va) and used in the following step was removed.

(b) Synthesis of imazamox (IVa)-Na

1327 g (16.6 mol) 50% aqueous NaOH were added to the aqueous layer of step (d) containing (Va), and the mixture was stirred for 30 minutes at 80⁰C.

At pH 7 toluene residues were stripped by lowering the pressure to 300 mm Hg. After completion of the cyclization reaction the mixture containing the sodium salt of imazamox was cooled to 60°C.

The reaction mixture was used without further purification the following acidification step. Yield 3.22 mol (IVa)-Na, determined by HPLC-assay, 84% (based on (VIa))

c) Synthesis of imazamox (IVa)

9616 g of the mixture from step (b) were charged into a vessel at room temperature. 3700 g H₂O and 1698 g sulfuric acid (98%) were added to the mixture at a temperature of 89°C resulting in a pH value of 3.2. The resulting slurry was cooled to 65°C and filtered.

The filter cake was washed with 3698 g of water at 60 to 65°C and the product wet cake was dried.

Yield: 1000 g (3.28 mol) (IVa) 83% (based on (VIa)).

Example 3

Synthesis of imazamox (IVa) from 5-methoxymethyl-2,3-pyridinedicarboxylic acid (Vla)-one pot procedure

2.1 1 g (10 mmole) of 5-methoxymethyl-2,3-pyridinedicarboxylic acid, 20 mL of toluene, 1.1 g (10.6 mmole) of acetic anhydride, and 0.14 g (1 .5 mmole) of 4-methylpyridine were charged at 25°C to a 100 mL three neck flask fitted with a mechanical stirrer, thermometer, and a reflux condenser. The slurry was heated to 50⁰C and held at that temperature for one hour. The reaction was then cooled to 25°C and 1.75 g of a 67% solution in toluene of 2-amino-2,3-dimethylbutyronitrile (10.6 mmole) was added over one minute. The reaction was held at 25 - 31⁰C for one hour. A solution of 0.54 g of water (30 mmole) with 0.41 g of 96% sulfuric acid (4 mmole) was added all at once and the mixture was heated to 50-55⁰C for two hours and then 65-70⁰C for two hours. 2.0 g of water was then added, followed by 5.6 g of 50% sodium hydroxide (70 mmole) and the reaction was heated to 65-70⁰C for 30 minutes. The reaction was then cooled to 50⁰C and 10 mL of water is added. The reaction was cooled to 22°C and the organic phase was removed from the aqueous phase. 96% sulfuric acid was added between 30 and 40⁰C to lower the pH to 3-4. An additional 5 mL of water was added. The resulting precipitate was filtered and washed with 3 x 10 mL water to afford 4.2 g of wet imazamox. The product was dried to provide 2.1 g (67% yield) of ma- terial. The structure was confirmed by NMR and MS.

Example 4 Preparation of 5-(methoxymethyl)-2,3-pyridinedicarboxylic acid (Via)

a) Synthesis of dimethyl 5-(bromomethyl)-2,3-pyridinedicarboxylate (Va) (50% conver- sion)

(IVa) (Va)

218.4 g (1 .0 mol) compound (Va) were dissolved in 1 139.0 g 1 ,2-dichloroethane (EDC) and 160.0 g water were charged and heated to 72°C (about 1-2°C below reflux). 14.4 g (0.075 mol) 2,2'-azobis(2-methylbutyronitrile) (Vazo 67) in 160.0 g EDC were added over 2 h at 72°C. After 30 minutes 143.8 g (0.9 mol) bromine were added over 2 h, under pH control (pH 5-7) by dosage of about 375.0 g aqueous NaOH (15%). The mixture was stirred over 1 h for reaction completion (HPLC assay). After cooling to 40⁰C the phases were separated.

b) Synthesis of [(5,6-dicarboxy-3-pyridyl)methyl] trimethylammonium bromide, di- methylether (Vlla)

288.1 g (1.0 mol)compound (Ilia) in mixture with di- and tribromination byproducts) in 3359.0 g EDC (organic phase from step a, including unreacted compound (Na) and higher brominated byproducts) were charged. The mixture was heated to 30⁰C and the vessel evacuated to 200 mbar. 70.9 g (1.2 mol) Trimethylamine (TMA) was added to the gas phase during 2 h at 40°C (closed system). The mixture was stirred 1 additional hour (HPLC conversion check: compound (Ilia) in solution < 0.1 %).

Excess TMA was distilled off together with EDC (mass: 40% of the EDC mass transferred to step 2 (1344 g) at 50-55⁰C (370-250 mbar). The pH of the distillate was < 9. 630.0 g water was sprayed to the wall so that the solid is dissolved and the mixture was transferred to the next vessel. The mixture was then stirred 0.25 h, and the lower organic phase was separated at 40⁰C. 320.4 g EDC were added. The mixture was stirred and the lower organic phase was separated at 40⁰C. The back extraction was repeated (40°C) with 320.4 g EDC. The 2 organic back extraction phase were combined with the first organic phase and recycled to the next bromination batch (af- ter addition of 50% fresh compound (Na) for a further cycle.

Steps a) and b) were repeated six times. In the last cycle no compound (Na) was added in step a) and 0.8 mol TMA were added in step b).

The overall conversion rate of compound (Ma) was 96.6 %. The yield of compound (Ia) (over 7 cycles) is 77.4 % at a purity of > 95 % (as determined by HPLC).

Bromide (Na), (0.41 mol) containing about 40% by weight of water, was taken up in methanol. Aqueous NaOH was added over 30 min at 35°C, and the mixture was stirred for an additional 15 min. NaOCH₃ in methanol was added over 20 min at 45°C.

The reaction mixture was moved to a Parr pressure reactor and heated to the reaction temperature (80 to 100⁰C). At about 60⁰C the reactor was closed, whereupon pressure built up reaching about 40 to 45 Psi at the reaction temperature. No external pressure was applied.

After 6 to 8 h, the reaction mixture was cooled to room temperature, treated with sulfuric acid to adjust the pH to a value from 1.5 to 2 and filtered to obtain a solid. The solid was washed with water and dried in a vacuum oven to obtain the title product as a white solid (mp 161 to 162°C) which was greater than 99% pure by HPLC analysis.

c) Synthesis of diacid (Vl)

(Via)

(Vila)

[5,6-Dicarboxy-3-pyridiyl)methyl] trimethyl ammonium bromide dimethyl ester (0.41 mol) containing about 40% by weight of water, was taken up in methanol. Aqueous NaOH was added over 30 min at 35°C, and the mixture was stirred for an additional 15 min. NaOCH3 in methanol was added over 20 min at 45°C.

Claims

1. A 2-[(1-cyanopropyl)carbamoyl]-5-methoxymethyl nicotinic acid of formula (I)

where

R³ is hydrogen or a cation.

2. The compound as claimed in claim 1 , where Z and Z¹ are H.

3. The compound as claimed in claim 1 or 2, where R¹ is CH(CHs)₂ and

R² is CH₃.

4. The compound as claimed in any one of claims 1 to 3, where

Z and Z¹ are H;

R¹ is CH(CH₃)₂;

R² is CH₃ and

R³ is H.

5. A process for preparing a 2-[(1 -cyanopropyl)carbamoyl]-5-methoxymethyl nico- tinic acid of formula (I) as claimed in any one of claims 1 to 4, comprising the step of (i) reacting a 5-methoxymethyl pyridine-2,3-dicarboxylic acid anhydride of formula (II),

wherein Z, Z¹ are as in formula (I),

with a 2-aminoalkane carbonitrile (III),

H₂N-CR¹R²-CN (III) where R¹ and R² are as in formula (I) in any one of claims 1 to 4.

The process as claimed in claim 5, where the ratio of anhydride (II) to aminonitrile (III) is 1 :0.

8-1.2.

The process as claimed in claim 5 or 6, which is carried out in a solvent selected from aromatic hydrocarbons, chlorinated aromatic hydrocarbons, chlorinated aliphatic hydrocarbons, acetic acid, and mixtures thereof.

The process as claimed in any one of claims 5 to 7, where either acetic acid is the solvent or 0.5 to 10 equivalents of acetic acid (based on (II)) are added to the solvent.

9. The process as claimed in any one of claims 5 to 8, where the reaction is carried out at a temperature in the range of from 40 to 120⁰C.

10. The process as claimed in any one of claims 5 to 8, where the reaction mixture is essentially free of pyridine, picolines and quinoline.

1 1. The process as claimed in any one of claims 5 to 10, comprising the steps of

(i-1 ) reacting a compound of formula (VII),

where

Z is H or halogen;

Z¹ is H, halogen, CN or NO₂;

Y¹ and Y² are each independently OR¹, NR¹R², or, when taken together, Y¹Y² is -O-,

-S- or -NR³-;

R¹ and R² are each independently H;

C₁-C₄ alkyl optionally substituted with C₁-C₄ alkoxy or phenyl optionally substituted with one to three C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups or halogen atoms; or phenyl optionally substituted with one to three CrC₄ alkyl groups, CrC₄ alkoxy groups or halogen atoms; and

R³ is H or Ci-C₄ alkyl,

in a methanol/H₂O mixture, comprising at least 20% by weight H₂O (based on the sum of water and bromide (VII)), with a base comprising MOCH₃ and/or MOH, where M is alkali metal or alkaline earth metal, under pressure in a closed vessel at a temperature of from about 75 to 1 10⁰C;

(i-2) reacting compound (Vl),

where Z is H or halogen;

Z¹ is H, halogen, CN or NO₂,

formed in step (i-1 ) with a dehydrating agent in the presence of a base, and a solvent selected from methyl tert. -butyl ether, diisopro- pylether, cyclopentyl methyl ether and mixtures thereof, to obtain anhydride (II), and

(i-3) reacting anhydride (II) with a 2-aminoalkane carbonitrile (III),

H₂N-CR¹R²-CN (III), where R¹ and R² are as in formula (I).

12. The use of a compound of formula (I) as claimed in any one of claims 1 to 4 for preparing a herbicidal imidazolinone of formula (IV),

wherein

Z, Z , R , R , R are as defined in formula (I) in any one of claims 1 to 4.

13. A process for manufacturing an amide of formula (V),

where Z, Z , R , R , R are as defined in formula (I) in any one of claims 1 to 4,

comprising the step of

(i) hydrolyzing the nitrile of formula (I) to obtain an amide of formula (V).

14. A process for preparing a herbicidal imidazolinone compound of formula (IV),

where Z, Z¹, R¹, R², R³ are as defined in formula (I) in any one of claims 1 to 4,

comprising the steps of

(i) hydrolyzing a nitrile of formula (I) according to any one of claims 1 to

4 to obtain an amide of formula (V) according to claim 13 and

(ii) reacting compound (V) with MOH/CH₃OH (where M is alkali metal, preferably Na or K) optionally followed by acidification to form the herbicidal imidazolinone (IV).

15. The process as claimed in claim 14, comprising the steps of

(i-1 ) preparing a compound of formula (I), as claimed in any one of claims

1 to 4 by reacting an anhydride of formula (II) according to claim 5 with an aminonitrile (III) according to claim 5, and

(i-2) hydrolyzing the compound of formula (I) thus obtained to yield an amido compound of formula (V) according to claim 13.