DE1518411C3 - N-Disubstituted aminoamic acids, processes for their preparation and use of these compounds - Google Patents

Description

I! c-

NH-N

IO

(D

C-OH

Il ο

A Ν —N

C-NH-N
^S C -OH

Il ο

Il

R,

Ν —Ν

(II)

(Π)

C.
O

R,

wherein Ri and R2 each represent an alkyl group with 1 to 12 Carbon atoms are or, together with nitrogen, a morpholinyl, pyrrolidyl or piperidyl radical form, and A

where Ri and R _{2 are} each an alkyl group having 1 to 12 carbon atoms or together with the nitrogen form a morpholinyl, pyrrolidyl or piperidyl radical, and A |

R ₃

CH-CH ₂

CH CH-> "

or

or

C = CH

I. R4

means in which R4 is hydrogen or a methyl group, R3 is hydrogen, a methyl group, a dodecenyl group, a phenyl group, an acetoxy group, a methylthio group, a dodecylthio group, a tolylthio group or a phenylthio group is.

2. Process for the preparation of the aminoamic acids of the general formula I, their salts and their Imides of the general formula II according to claim 1, characterized in that in per se as is known, the anhydride of the corresponding substituted or unsubstituted dicarboxylic acid with the corresponding 1,1-disubstituted hydrazine or the corresponding monosubstituted Reacts amine and the substituted acid obtained, optionally in a salt transferred or for imide formation with acetic anhydride treated.

40

45

The invention relates to new N-disubstituted aminoamic acids of the general formula I, their salts and C = CH- R4

means in which R4 is hydrogen or a methyl group, R3 is hydrogen, a methyl group, a dodecenyl group, a phenyl group, an acetoxy group, a Methylthio group, a dodecylthio group, a tolylthio group or a phenylthio group.

The invention also relates to a process for the preparation of these compounds. This procedure is characterized in that the anhydride of the corresponding substituted in a conventional manner or unsubstituted dicarboxylic acid with the corresponding 1,1-disubstituted hydrazine or the corresponding monosubstituted amine reacts, and the substituted acid obtained is optionally in transferred to a salt or reacted with acetic anhydride for the production of imides. In the case of manufacture of the N-disubstituted <x-aryl or alkylthiosuccinimides is the corresponding N-disubstituted one which is free in the α-position Acid imide treated with thiophenol, thiotoluene or methyl or dodecyl mercaptan. The corresponding Alkali, ammonium or amine salts, e.g. B.

the sodium, potassium, ammonium, methylammonium, dimethylammonium, trimethylammonium, ethylammonium, Ethanolammonium, diethanolammonium or triethanolammonium salts can easily be added directly from the acid and a selected base such as an alkali hydroxide, carbonate, ammonia or a Amine.

The course of the reaction in the formation of N-dimethylaminomaleamic acid and the N-dimethylamino

1Ö 1Ö411

maleinimids is represented by the following formein:

H-C

Il

H-C

O + H ₇ NN

Il ο

CH ₃

CH ₃

N-N

CH,

CH,

aromatic ring is. In the chemical compounds of the present invention, the intervening group containing two carbon atoms is part of a functional aliphatic moiety.
Examples of substances according to the invention are:

1. N-Dimethylaminomaleamic acid

2. N-dioctylaminomaleamic acid

3 .. N-Didodecylaminomalein-

amic acid
4. H- (4-MorphoIinyl) -male-

amic acid
5. N-dimethylaminomaleimide

6. N- (4-Morpholinyl) maleimide

7. Sodium N-dimethylaminomaleinamate

8. Dimethylaminosuccinamic acid

9. N-Dimethylamino-1-dodecenyl succinamic acid

10. N-dimethylamino-1-acetoxy-

succinamic acid

11. N-Dimethylamino-1-phenylsuccinamic acid

12. N-dimethylaminomethyl maleamic acid

13. N-dimethylaminosuccinimide

14. N-Dimethylamino-1-phenylthiosuccinimide

15. Diethanolammonium N-dimethylaminosuccinamate

16. Sodium N-dimethylamino-1-phenylthiosuccinamate

The products prepared by the above process are used as growth regulators and Fungicides useful.

By examining a number of N-substituted amino acids and their imides and salts was found that the essential structural arrangement for effectiveness as growth regulators is in which the carboxyl group of the acid is replaced by two carbon atoms from the group

OH

C — Ν — Ν

R,

R ₂

is removed and the intervening group containing two carbon atoms is not part of a F = 124 to 126 ° C viscous oil
viscous oil

F = 165 to 167 ° C

(Decomp.)

F = 83 to 84 ° C

F = 101 to 103 ⁰ C

aqueous solution

F = 154-156 ° C viscous oil
viscous oil
F = 130 to 32 ° C. CF = 125 to 126 ° C

F = 35 to 40 ° C

(Wax)

F = 70 to 71 ° C

aqueous solution
aqueous solution

The following list shows the good fungicidal activity of a number of compounds according to the invention, which was tested against Alternaria solani on tomato plants (using 2000 ppm), specified:

1. N-Dimethylaminomaleamic acid

4. N- (4-Morpholinyl) maleamic acid

6. N- (4-Morpholinyl) maleimide

11. N-Dimethylamino-1-phenylsuccinamic acid
14. N-Dimethylamine-1-phenylthiosuccinimide

Annihilation,%

75

90

63

90

94

The preparation of the substances according to the invention are explained in more detail in the following examples.

example 1
Manufacture of N-dimethylaminomaleamic acid

A 3 liter three neck flask containing a solution of Containing 294 g (3.0 mol) of maleic anhydride in 300 g of acetonitrile is immersed in an ice bath. In the course of '/ 2 hours is a solution of 180 g (3.0 mol) of 1,1-dimethylhydrazine in 100 g of acetonitrile from a Adding a dropping funnel, the reaction mixture being stirred very vigorously. During this encore

the temperature of the reaction mixture does not exceed 30 ⁰ C. Shortly before the end of the addition, a large amount of cream-colored crystals separate from the solution. After the addition is complete, stirring is continued for a further 20 minutes, and then 700 ml of ether are added in order to achieve further excretion of the reaction product from the solution. Filtering this reaction mixture gives a filter cake which, after washing three times with 100 ml of ether each time, gives an amount of 428 g (90% yield) of N-dimethylaminomaleamic acid with a melting point of 121 to 124 ° C.

After recrystallization from acetone, a sample of this substance had a melting point of 123 to 125 ° C.

Analysis: Calculated for C ₆ H ₁₀ N ₂ O ₃ , 45.6% C, 6.3% H, 17.7% N; found 45.9% C, 6.5% H, 17.7% N.

Example 2

Preparation of N- (4-morpholinyl) maleamic acid

The N- (4-morpholinyl) -maleamic acid is produced by reacting N-aminomorpholine with maleic anhydride obtained by following the procedure of Example 1. The compound produces colorless crystals with a F. 172 bis 174 ° C.

Analysis: Calculated for C ₈ H ₁₂ N ₂ O ₄ , 48.0% C, 6.0% H, 14.0% N! Found 48.3% C, 6.1% H, 13.5% N.

The N- (1-pyrrolidyl) maleamic acid and N- (1-piperidyl) maleamic acid can be prepared in the same way from N-aminopyrrolidine or N-aminopiperidine and maleic anhydride getting produced.

Example 3
Preparation of N-dimethylaminomaleimide

255 g (2.5 mol) of acetic anhydride are added to 316 g (2.0 mol) of N-dimethylaminomaleamic acid with a melting point of 121 to 124 ° C. (prepared according to Example 1) in a 1-1 Erlenmeyer flask. In half an hour this mixture is gradually heated to 75 ° C on a steam bath. When the temperature reaches 65 to 70 ° C, all of the solid components dissolve into a clear amber solution. After this solution was maintained for half an hour at 75 to 8O ⁰ C, allowed to cool within about one hour to 45 to 50 ° C.

The solution is then vacuum distilled using a short (8 ") distillation column. After distilling off in acetic acid and acetic anhydride, the dark liquid residue is under brought to a pressure of 2 to 3 mm to a temperature of 70 ° C. The yellow-orange liquid distillate in an amount of 200 g is then used at a temperature of the distillation column in the range of 68 up to 84 ° C and a pressure of 2 to 3 mm. When the distillate has cooled, it solidifies a yellow-orange crystalline mass. The residue in the distillation flask consists of 30 to 40 g a black brittle resin that is easily soluble in water.

The distillate obtained is then successively heated to 65 to 70 ° C. with several times 500 ml of cyclohexane while stirring. This results in a two-phase system in which the cyclohexane layer has a clear golden yellow color. The lower layer consists of dark brown viscous oil. After stirring has been stopped and the layers have separated cleanly, the hot cyclohexane layer is decanted. After extracting four times in the same way, the combined cyclohexane solutions (approx. 2.51) are cooled in an ice bath and give a precipitate of 133 g (48% yield) of N-dimethylaminomaleimide in the form of long, bright yellow needles with a melting point of 81 to 83 ° C. By recrystallizing a sample of this substance from cyclohexane, an analytical sample with a ^{temperature of 83 to 84 °} C. is obtained, which gives the following elemental analysis: Calculated for C ₆ H ₈ N ₂ O ₂ , 51.4% C, 5.7% H, 20.0% N; found 51.7% C, 5.9% H, 19.5% N.

■ 5 Example 4

Production of N-dimethylaminosuccinamic acid

A solution of 30 g (0.50 mol) 1,1-dimethylhydrazine in 50 g acetonitrile is added to a solution of 50 g (0.5 mol) of succinic anhydride in 150 g of acetonitrile. After the exothermic reaction has subsided, the mixture is cooled in an ice bath and the precipitate collected by filtration. It ^; a yield of 74 g (92%) of N-dimethylaminosuccinamic acid in the form of colorless crystals with a melting point of 154 ° to 156 ° C. is obtained. After recrystallization from ethanol, a sample of this substance gives colorless crystals with a F. 154 to 155 ^° C.

35

Example 5

Production of N-dimethylaminosuccinimide

To 64 g (0.40 mol) of N-dimethylaminosuccinamic acid (prepared according to Example 4) 80 g (0.80 Mol) acetic anhydride given. If this mixture is heated to 90 to 100 ° C for 15 to 20 minutes, a clear yellow solution is obtained. This is held for 30 minutes at 100 to 110 ° C, then slowly Cooled (within 30 to 40 minutes) to 50 to 55 ° C. Acetic acid and acetic anhydride are then removed by distillation at a pressure of 5 to 10 mm. The remaining liquid ( is then held at 80 to 85 ° C for 15 minutes under a pressure of 3 to 4 mm. There will be 53 g of one Clear light amber colored liquid which, after cooling in an ice bath, turns into a crystalline Solidified mass. After this substance has been recrystallized from ether, 32 g of N-dimethylaminosuccinimide are obtained Obtained as colorless needles with a melting point of 53 to 55 ° C.

Example 6

Production of N-dimethylaminoa-dodecenylsuccinamic acid

Dodecenylsuccinic anhydride, which is traded as “tetrapropenylsuccinic anhydride” _{and contains a Ci 2} H23 group in the α position, was reacted with the equimolar amount of 1,1-dimethylhydrazine in acetonitrile. A clear yellow solution is obtained as the reaction product. After the acetonitrile has been removed from this solution by vacuum distillation, the N-dimethylamino-α-dodecenylsuccinamic acid is obtained as a clear, yellow, viscous liquid.

Example 7

Production of N-dimethylaminooc-acetoxysuccinamic acid

To a solution of 15 g (0.10 mol) of oc-acetoxysuccinic anhydride with a melting point of 56 to 57 ° C. in 20 g of acetonitrile, 6.0 g (0.10 mol) of 1,1-dimethylhydrazine are added in small portions. An ice bath was used during mixing in order to avoid the temperature of the reaction mixture exceeding ^{35 ° C.} After this mixture has been allowed to stand for one hour, the acetonitrile is removed by vacuum distillation. By keeping the residue for two hours at a pressure of 2 to 3 mm at a temperature of 40 to 45 ° C, 21 g of a viscous light brown liquid are obtained, which partially crystallizes when left to stand for several hours.

Example 8

Production of N-dimethylaminoa-phenylthiosuccinimide

To a solution of 14 g (0.10 mol) of N-dimethylaminomaleimide (prepared as in Example 3) in 20 g of benzene, 11 g (0.10 mol) of thiophenol (phenyl mercaptan) given.

After this mixture is heated to 60 to 65 ° C, a few crystals of benzoyl peroxide are added and the mixture is left to stand for IV2 hours. After the benzene is removed by distillation, the residue becomes 1/2 hour at a pressure of 2 to 3 mm held at 65 to 70 ° C. The remaining yellow liquid (24 g) is dissolved in 70 ml of warm ethanol solved. After cooling this solution in an ice bath, the solid precipitate obtained is filtered off collected.

There are 17 g N-dimethylamino-.alpha.-phenylthiosuccinimid obtained as colorless crystals with the F. 70-71 ⁰ C. The sodium salt of N-dimethylamino-aphenylthiosuccinamic acid can be prepared from the N-dimethylamino-a-phenylthiosuccinimide by reaction with sodium hydroxide, and the free acid can be prepared from the sodium salt by treatment with a strong inorganic acid, e.g. B. hydrochloric acid can be obtained.

The compounds according to the invention can be used in various ways as growth regulators in plants be applied, e.g. B. in seeds, flowers, fruits, vegetables, roots and foliage. The seeds can directly with the compound before sowing or the seeds can be treated with the substance can be treated by incorporating them into the soil before or after sowing the seeds. On the Plants can use the compounds e.g. B. be applied as dust with an indifferent carrier, z. B. with powdered mica, talc, pyrophyllite and clays, or in an aqueous preparation, optionally with small amounts of surface-active anionic, nonionic or cationic wetting agents mixed.

The compounds can also be dissolved in organic solvents, such as acetone, benzene, Kerosene, and the solutions of the substances can be in water with the help of surface-active agents such. B. according to US Patent 25 47 724, columns 3 and 4 are emulsified. The effectiveness of the invention Substances as growth regulators for plants and especially as agents for inhibiting the Growth (achievement of dwarfism) is shown in the following examples.

Example A.

This example shows the treatment of growing plants with the substances according to the invention.

Aqueous solutions or dispersions of the substances are produced which contain 5000 parts per million (ppm) of the various substances according to the invention and a small amount of surfactant (Polyoxyethylene sorbitol monolaurate), which is known to be inactive in these experiments.

Peanut plants in the 2 to 3 leaf stage were sprayed with aqueous compositions so that they drained off. The aqueous formulations contained 5000 ppm

N-dimethylamino maleamic acid,
N-di-n-octylaminomaleamic acid,
N-dimethylaminomethylmaleamic acid,
N-dimethylaminomaleimide,

N- (4-morpholinyl) maleamic acid,
N- (4-morpholiny l) -maleimide,
N-dimethylaminosuccinamic acid,
N-dimethylaminosuccinimide,

N-dimethylamino-a-dodecenylsuccinamic acid,
N-dimethylamino-a-phenylsuccinamic acid and
N-dimethylamino-a-phenylthiosuccinimide.
The treated plants and untreated control plants were then placed in a room with 100% humidity and a temperature of 24 ° C. After 24 hours they were taken out and placed in a greenhouse. The plants were then examined 2 to 4 weeks after application of the substances. The intermediate nodes of the peanut plants treated with the substances were found to be dwarfed or shortened in comparison with the untreated control plants.

Other crops, such as soybeans, beans (pinto beans), and pumpkin (curcurpitaccae maxima) show similar dwarfism on treatment with the substances according to the invention.

Example B.

This example shows the direct treatment of seeds with the substances according to the invention. Bean seeds (Pinto beans) is immersed in 100 ml of an aqueous composition containing 1000 parts per million of the following compounds which are similar to the compositions of Example A were manufactured:

N-dimethylaminomaleamic acid,
N-di-n-dodecylaminomaleamic acid,
N-dimethylaminomaleimide,
N- (4-morpholinyl) maleamic acid,

N-dimethylaminosuccinamic acid,
N-dimethylamino-a-dodecenylsuccinamic acid,
N-dimethylamino-a-acetoxysuccinamic acid,
N-dimethylaminosuccinimide,
N-dimethylamino-a-phenylthiosuccinimide.

After 4 hours the seeds were removed, washed well with water for several minutes and placed in Soil planted in 4 "pots. Untreated

■ Seeds were planted in a similar way. Observations 2 to 4 weeks after planting indicated decisive Dwarfism of the plants treated with the substances compared with untreated ones Control plants.

709 619/7

Example C

This example shows the treatment of seeds with the substances by adding the substances to the soil be incorporated.

2/10 g of each of the following dry substances were evenly mixed with 110 g of dry sand mixed:

N-dimethylaminomaleamic acid,

N-dimethylaminomaleimide, N-dimethylaminosuccinamic acid,

N-dimethylaminosuccinimide and

N-dimethylamino-oc-phenylthiosuccinimide.
The sand and chemical mixes were then added to 2038 g each of a 4: 1 soil and sand mix and rolled for 5 minutes. After this time the substances were evenly distributed throughout the soil and sand mixture in a ratio of 100 parts of the substance per million parts of other soil or sand Bean seeds (pinto beans) have been potted. Bean seeds were also placed in pots containing untreated control soil with sand. Observations after 2 to 4 weeks showed clear dwarfism of the plants from seeds which were planted in the soil with the

10

ßen treated substances was in comparison with the plants from seed, which in untreated Control floor was inserted.

Example D

A number of compounds according to the invention have been found on peanut plants (Arachis hypogaea L.) sprayed and with a spray test carried out under the same conditions with bis-maleamic acid according to British Patent 790646. The test carried out corresponds to example 1 and was carried out as follows:

Water solutions or dispersions each containing 4000, 2000, 1000 and 500 ppm of the active ingredient were prepared and treated with a small amount of the surfactant Triton X-100 (isooctylphenyl polyethoxyethanol) offset. Peanut plants of the same size (140 to 165 mm), each with about 6 to 9 leaves, were sprayed with the aqueous solutions until they ran off. The plants were immediately after Spray returned to the greenhouse. The observations and measurements were made 4 weeks after of the treatment and can be seen in the table below. From the data are the technical advantages of the agents according to the invention over the control and the known Bis-maleamic acid clearly visible.

Chemicals

crowd
ppm

Average height Fifth intermediate node distance *)
mm

Growth inhibition **)

Phytotoxicity

Controls

320 46

N-dimethylaminosuccinamide 4000 - not tested - - acid 2000 225 3.2 60 0 1000 225 10 60 0 500 225 16 60 0 N-dimethylaminomaleimide 4000 240 11 ,: i 50 ■ little 2000 225 26th 60 small amount 1000 250 18.7 40 small amount 500 265 18th 30th in traces N-dimethylaminosuccinimide 4000 not tested 0 2000 255 23.5 40 0 1000 255 25th 40 0 500 280 40 25th 0 N-dimethylaminophenylthio- 4000 not tested succinimide 2000 280 36.7 ■ 25th 0 1000 305 50 10 0 500 305 50 10 0 Bis-maleamic acid 4000 315 50 5 small amount 2000 315 54 5 0 1000 315 52.5 5 0 500 315 49 5 0

*) The intermediate nodes were counted up from the base of the plants, the 5th intermediate node is between

the 4th and 5th leaves above the cotyledons.
**) The growth inhibition is based on the difference in length of the new one obtained after spraying the plant

Growth compared to that of the untreated controls.

Example E.

Furthermore, the effect of N-Dimethy! - aminosuccinamic acid (hereinafter referred to as B 995) having the effect of maleic hydrazide (hereinafter referred to as MH-30) on various Plants compared.

B 995 reduces the growth of chrysanthemum stems. MH-30 prevents the vegetative Growth too, but it disrupts flower development, causing late blooming with poor quality shaped flowers is produced. So this substance cannot be used for just that To reduce the growth in length of the stems.

The growth of apple trees can be controlled by spraying with B 995 at the beginning of the season

to prevent the rapid growth of wood saplings in early summer.

The application of MH-30 interrupts the growth the branches of the trees, but also prevents the formation of buds, from which a results in deteriorated harvest. In contrast, B 995 favors the formation of flowers and the Fruit sets and thereby increases the harvest.

But there is also a difference in the quality of the apples, because the storage quality of the apples is indicated by the firmness of the fruit at harvest.

Both substances, MH-30 and B 995, increase the firmness of apples when they are in midsummer be applied. However, the fruits treated with MH-30 have an early climacteric, namely an increase in breathing at maturity, reducing the

Fruits become very susceptible to putrefactive organisms, while on the other hand B 995 delays the climacteric thus extending the shelf life of the fruit.

Alfalfa, Medicago sativa and other forage crops are beneficial when treated with B 995 Increase result in the ratio of leaf to stem, thereby giving rise in the ratio of leaf to stalk, which increases the nutritional value of the hay

ίο will. The application of MH-30 is unsuccessful here.

Example F

The table below provides information on the action of further compounds according to the invention compared to the effect of 2-chloroethyltrimethylammonium chloride (CCC = Cycocel).

connection

concentration
in parts per
million

Stunted growth
for peanut plants in%

(2-chloroethyl) trimethylammonium chloride

N-dioctylaminomaleamic acid

N-Didodecylaminomaleamic acid

N- (4-Morpholinyl) maleamic acid

N-dimethylaminomaleimide

N-dimethylaminosuccinamic acid

N-dimethylamino-1-acetoxysuccinamic acid

N-dimethylaminocitraconamic acid

N-dimethylaminosuccinimide

N-dimethylaminophenylthiosuccinimide

2000 0 2000 40 2000 46 2000 82 2000 60 2000 80 2000 61 2000 52 2000 40 2000 25th

Example G

The effects of N-dimethylaminosuccinamic acid and, for comparison, of (2-chloroethyl) trimethylammonium chloride and N-dimethylaminohexahydrophthalamic acid, which are used as sprays on peanut plants were carried out in concurrent greenhouse experiments.

The test compounds were run in water at a concentration of 5000 parts / million Weigh in 0.5 g of compound to which one drop of surfactant (about 30 mg) is added and then made a suspension in 100 ml of water. Done by adding water Dilutions to 2000 parts / million and 500 parts / million.

The aqueous preparations were placed on multiple pots of Virginia Runner peanut seedlings sprayed on. The sprays were applied by means of a spray atomizer, the 15 ml of spray solution in 15 Seconds at a distance of 30 cm from the plants. This spray was sufficient to get that To wet leaves.

The treated plants were immediately placed in a at 24 ° C and 90 to 99% relative humidity held chamber brought to the ideal conditions for a period of 20 hours to result in rapid absorption of the materials by the plant leaves. The plants were then placed in a 24 brought to a greenhouse kept at 27 ° C for a period of 25 days. After this During this period, the studies were carried out to determine the amount of new growth during this period determine. The percent growth retardation was calculated in the following way:

% Inhibition = 100

1-new growth of the treated plants
new growth of comparative flanges.

Chemical name Spray con At first End growth Hem centering height height increase mung Parts / million cm cm cm % (25 days)

(2-chloroethyl) trimethylammonium chloride

N-dimethylaminosujcinamic acid

control

5000

2000

500

5000

2000

500

60 110 50 12th 60 117 57 0 60 147 87 (0) 60 70 10 82 60, 72 12th 79 60 65 5 91 60 117 57 0

continuation

N-dimethylaminohexahydrophthalamic acid

N-dimethylaminosuccinamic acid

control

Chemical designation Spray con At first End growth Hem centering height height increase mung Parts / million cm cm cm % (25 days)

5000

2000

500

5000

2000

500

50 107 57.5 26th 50 100 50 35 47 97 50 35 45 55 10 87 47 60 13th 83 50 65 15th 81

50

130

77.5

These tests show the lack of effectiveness of the comparison compounds on peanut plants, where, however, the compound of the invention is effective.

Claims (1)

Patent claims: 1. N-disubstituted aminoamic acids of the general Formula I, its salts and its imides of the general formula II their imides of the general formula II,
OR ₁