Inhibitory Activities of 3-Thiophenecarboxylic Acid and Related Compounds on Plant Growth

Asada

2005

The application of herbicides or plant growth regulators to crop production is considered essential for the efficiency of the agricultural economy.1) For example, chloroacetamide herbicides, such as acetochlor (1), alachlor (2), and dimethenamide-P (3), are widely used for weed management in corn production to promote sustainable agriculture.2) SMetolachlor (4), which is the S-isomer of metolachlor, shows growth inhibition of seedling-shoots and root tissues soon after germination. 3)Agrochemical-related furan derivatives, 3-(furan-2-yl)-propanamides (5a) and 3-(furan-2-yl)propanoates (5b), have been synthesized and found to have moderate phytogrowthinhibitory activity.4) It has been suggested that the asymmetric carbon at the 2-position of 2-substituted propionic acids such as 2-(2,4-dichlorophenoxy)propanoic acid (2,4-DP, 6b) plays a key role in the root-withering of perennial weeds, because of its significance in translocation of herbicides within plants. 5)Recently, we developed an improved preparation of racemic 2-amino-3-(furan-2-yl)propanoic acid (furylalanine) (7a), 6) and we used the same approach for synthesis of 2-(chloroacetamido)-3-(furan-2-yl)propanoic acid [N-(chloroacetyl)furylalanine] (7b) for the evaluation of plant growthinhibitory activity. We found that 7b inhibited the root growth of rape seedlings by about 51% at the concentration of 1.0ϫ10As a continuation of that work, we have investigated the biological activity of various N-substituted 2-(2-chloroacetamido)-3-(furan-2-yl)propanamides (16-18).Here, we report the preparation of the acid amides 16, 17 and 18, and the results of examination of their root growthinhibitory activity in rape seedlings.Preparation of N-Substituted 2-(2-Chloroacetamido)-3-(furan-2-yl)propanamides (16-18) The key intermediate in this work was racemic 2-amino-3-(furan-2-yl)propanoic acid (furylalanine) (7a), which was synthesized in 77% yield by the reduction of 3-(furan-2-yl)-2-(hydroxyimino)propanoic acid with zinc dust and formic acid in the presence of a catalytic amount of iron dust at 60°C for 2 h. 6) Protection of the amino nitrogen of the furylalanine (7a) with tertbutoxycarbonyl (Boc) using di-tert-butyl dicarbonate [(Boc) 2 O], and activation of the carboxylic acid of 7a using 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide · hydrochloride (EDCI · HCl), followed by condensation with amines (9, 11, 13), provided the corresponding acid amides (16-18), as shown in Table 1.The reaction of 3-or 4-halogen-substituted anilines with 2-(tert-butoxycarbonylamido)-3-(furan-2-yl)propanoic acid (Boc-furylalanine) (8) 8) give the corresponding N-substituted Boc-furylalanine acid amides (10a, c-d, f-g, i-p) in 37-98% yield. However, when 2-fluoro-(9b), 2-chloro-(9e) or 2-bromoanilines (9h) were used as the amine component, the desired Boc-furylalanine acid amides (10b, e, h) were not obtained owing to the weaker nucleophilicity of the amines. On the other hand, alkyl substituted anilines such as 2-ethylaniline (9k), 2,6-diethylaniline (9n), 2-ethyl-6-methylaniline (9o)...

Section: Preparation Of N-substituted 2-(2-chloroacetamido)-3-(furan-mentioning

confidence: 99%

Preparation and Root Growth-Inhibitory Activity of N-Substituted 2-(2-Chloroacetamido)-3-(furan-2-yl)propanamides

Asada

2005

“…Root Growth-Inhibitory Activity This activity was assayed according to the reported procedure 22) using seeds of rape, Brassica campestris L. (Brassicaceae), as a dicotyledon. The root length (in millimeters) of the seedlings was measured and averaged for each group.…”

Section: Preparation Of 2-(haloacetylamino)-3-(2-furyl)propanoic Acidmentioning

confidence: 99%

Synthesis and Root Growth-Inhibitory Activity of 2- and 3-(Haloacetylamino)-3-(2-furyl)propanoic Acids

Nakamura

Masai

2003

Compounds of the chloroacetamide family are major preemergence herbicides for control of seedling grass in corn and soybean crops, and are among the most widely used herbicides in the world.1,2) For example, the thiophene derivative dimethenamid [2-chloro-N-(2,4-dimethyl-3-thienyl)-N-(2-methoxy-1-methylethyl)acetamide] (1) is used for control of annual grasses and certain broadleaf weeds, primarily in corn and soybeans and also in peanuts. [3][4][5][6][7] In addition, thenylchlor [2-chloro-N-(3-methoxy-2-thienyl)methyl-2Ј,6Ј-dimethylacetanilide] (2) having a chloroacetamido moiety shows high herbicidal activity for barnyard grass in paddy fields. [8][9][10][11][12] In the course of work on furan derivatives as plant growth regulators, Tamari reported that 3-(2-furyl)propanoic acid (3) has a weak plant growth-inhibitory activity.13) This stimulated Kato et al. to examine the phytogrowth-inhibitory activity of 3-(2-furyl)propanoates (4) and 3-(2-furyl)propanamides (5), though these compounds proved not to have high activity. 12)We hoped to find a new lead compound by introducing a chloroacetylamino group into 3-(2-furyl)propanoic acid (3). Thus, we set out to prepare 2-and 3-(chloroacetylamino)-3-(2-furyl)propanoic acids (6a, 7a) 14) and to examine their root growth-inhibitory activities in rape seedlings.Preparation of 2-(Haloacetylamino)-3-(2-furyl)propanoic Acids (6) We initially considered the synthesis of 2-(chloroacetylamino)-3-(2-furyl)propanoic acid (6a) by utilizing diethyl formamidomalonate (8) to prepare 2-amino-3-(2-furyl)propanoic acid 15) (12), followed by chloroacetylation of 12 using chloroacetyl chloride. However, 8 is expensive, so we decided to employ the (chloroacetylamino)propanedioic acid diethyl ester (15a) route shown in Chart 2.First of all, 15a was synthesized in 90% yield by the reaction of diethyl aminomalonate hydrochloride (14) with chloroacetyl chloride in the presence of triethylamine, according the procedure of Sheehan and Bose. 16) We found that the reaction of 14 with chloroacetic acid using 1,1Ј-oxalyldiimidazole (ODI) 17) as a condensing reagent resulted in the formation of 15a in 58% yield accompanied with a tarry material. This result suggest that 15a is unstable in the presence of basic reagents such as ODI or imidazole.Next, synthesis of 2-(chloroacetylamino)-2-(2-furylmethyl)propanedioic acid diethyl ester (16a) was successfully achieved by means of the following reaction. Treatment of 2-bromomethylfuran 18) (9) derived from 2-furylmethanol (13) with 2-(chloroacetylamino)propanedioic acid diethyl ester (15a) at 70°C for 2.5 h in the presence of sodium ethoxide as a base gave a 61% yield of 16a. This diester (16a) was hydrolyzed with 10% NaOH solution for 24 h at room temperature to give 2-(chloroacetylamino)-2-(2-furylmethyl)propanedioic acid (17a) in 76% yield.Concerning the experimental conditions for the decarboxylation of propanedioic acid derivatives to give the corresponding monoacid derivatives, the literature contains a variety of procedures, such as 1) refluxing f...

“…Found: C,42.09;H,3.71;N,9.76. N-(4-Chloro-2-benzothiazolyl)-2-acetylamino-2-ethoxycarbonyl-3-(2-furyl)propanamide (8i) 8i was prepared as above through the reaction of the half acid (3b) (2.1 g, 8 mmol) with 2-amino-4-chlorobenzothiazole (13i) (1.63 g, 8.8 mmol) 15) A DMSO solution (1.0 ml) containing an amide derivative (8a-i) or DMSO alone (1.0 ml) as a control was diluted in 100 ml of sterilized agar (0.8%, Nacalai Tesque, Inc.) to give concentrations of 5ϫ10 Ϫ5 M, 1.0ϫ10 Ϫ4 M, 5ϫ10 Ϫ4 M and 1.0ϫ10 Ϫ3 M. Agar containing a test chemical or DMSO as a control was poured into a sterilized 500 ml culture jar. Then 20 seeds of each plant species, sterilized with 70% ethanol and 1% NaClO, were put on the agar and left for seven days (A. tuberosum; ten days) at 25°C under a relative humidity of 60% and a light intensity of 127 mmol · m Ϫ2 · s Ϫ1 .…”

Section: A)mentioning

confidence: 99%

“…Root Growth-Modulating Activity This activity was assayed according to the reported procedure 15) using seeds of rape, Brassica campestris L. (Brassicaceae), as a dicotyledon and leek, Allium tuberosum ROTTLER (Lilliacea), as a monocotyledon. The root length (in millimeters) of the seedlings was measured and averaged in each group.…”

mentioning

confidence: 99%

Preparation and Root Growth-Modulatory Activity of N-Substituted 2-Acetylamino-2-ethoxycarbonyl-3-(2-furyl)propanamides.

Akiyama

Masai

2001

Herbicides and plant growth regulators are widely used in crop production to improve productivity.1) Repeated use of the same herbicide or herbicides with the same mechanism of action, however, can lead to the appearance of weed species with tolerance to the applied agrochemicals, such as sulfonylurea-resistant paddy weeds or triazine-resistant weeds.2) Therefore, the continued development of novel herbicides and plant growth regulators is essential to supplement the current limited treatment options for resistant weeds. 1)We are interested in furan-containing structures, since it has been reported that L-3-(2-furyl)alanine (1) 3) used as a 500 mg/l spray on tomatoes completely prevented infection by Phytophthora infestansa, 3a) and L-3-(3-furyl)alanine (2) has fungicidal activity.4) These compounds (1, 2) were prepared from 2-(2-furylmethyl)-and 2-(3-furylmethyl)-2-acetylaminopropanedioic acid diethyl esters (3a, 4), respectively.In addition, 3-(2-furyl)propionic acid (5) was proven to be a weak growth accelerator by Tamari. 5) On the basis of this report, Kato et al. examined the phytogrowth-inhibitory activity of 3-(2-furyl)propionates (6) and 3-(2-furyl)propionamides (7). However, they did not show a remarkable herbicidal activity. 6)In this study, we examined the possibility that 2-acetylamino-2-ethoxycarbonyl-3-(2-furyl)propanamides (8) 7) having one ester group and two amide groups at the same carbon, might have plant growth-regulatory activity. We report herein the preparation of the diamides (8), and their testing in germination assays using rape and leek seeds.Preparation of N-substituted 2-acetylamino-2-ethoxycarbonyl-3-(2-furyl)propanamides (8) The synthetic route reported here was designed to prepare a series of test diamides (8) from the half acid (3b) obtained via the diester (3a), 8) as shown in Chart 2. Compound 3a has been synthesized from the reaction of diethyl acetamidomalonate with 2-(chloromethyl)furan (10a), itself obtained from the reaction of 2-furylmethanol (9) with thionyl chloride in the presence of pyridine. 9) However, 10a is extremely unstable and decomposes during purification by distillation to give hydrogen chloride, which catalyzes polymerization of the furan ring with explosive violence.10) To avoid this difficulty, we used 3-(bromomethyl)furan (10b) 11) as an equivalent of 10a. An important consideration is that the procedure for the preparation of 10b does not require a base such as pyridine as a scavenger of hydrogen chloride. 11a)First, 2-furylmethanol (9) in THF was allowed to react with phosphorus tribromide at 0°C for 1.5 h to yield the corresponding bromo compound (10b), which could be extracted from the reaction mixture with ether, and used without further purification. Then, 10b was directly treated with diethyl acetamidomalonate at 70°C in the presence of sodium ethoxide as a base to afford the corresponding diethyl ester (3a) in 81% yield. The success of this reaction using the bromo compound (10b) in place of the chloro compound (10a) allowed us to develop a con...