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

Abstract

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...

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

“…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 1.0ϫ10 Ϫ4 M. 7) As a continuation of that work, we have investigated the biological activity of various N-substituted 2-(2-chloroacetamido)-3-(furan-2-yl)propanamides (16)(17)(18).…”

Improved Preparation of Racemic 2-Amino-3-(heteroaryl)propanoic Acids and Related Compounds Containing a Furan or Thiophene Nucleus

“…6) We have recently reported that 2-(chloroacetylamino)-3-(furan-2-yl)propanoic acid (2) showed root growth-inhibitory activity towards rape seedlings. 7) As a continuation of that work, we have investigated a convenient route to a key intermediate, namely, racemic 3-(furan-2-yl)alanine (1a). This furan derivative (1a) has been synthesized in several ways, e.g., (i) diketopiperazine method, 8) (ii) hydantoin method, 9,10) (iii) rhodanine method, [11][12][13] and (iv) halomethylfuran-acylamidomalonate method.…”