n -Butyl 5-Chloro-2-pyrimidoxyacetate—A Plant Growth Regulator Analog

Abstract

Since the first demonstration of plant growth stimulation by substituted phenoxyacetic acids (1), much attention has been directed toward this series of compounds in an attempt to correlate the position and type of substituent with observed growth promotion. The results of the many investigations aimed at the elucidation of the mechanism of growthregulator action have been resolved into three general theories.One of these theories (2) supposes that there is a chemical reaction between the regulator and appropriate groups, probably nucleophilic, on some plant substrate, resulting in the formation of new convalent bonds. It has been shown that the most likely point of attack on the ring is at the positions ortho to the ether oxygen. Another theory (3)Since the first demonstration of plant growth stimulation by substituted phenoxyacetic acids (1), much attention has been directed toward this series of compounds in an attempt to correlate the position and type of substituent with observed growth promotion. The results of the many investigations aimed at the elucidation of the mechanism of growthregulator action have been resolved into three general theories.One of these theories (2) supposes that there is a chemical reaction between the regulator and appropriate groups, probably nucleophilic, on some plant substrate, resulting in the formation of new convalent bonds. It has been shown that the most likely point of attack on the ring is at the positions ortho to the ether oxygen. Another theory (3) Fig. 1. Structural formulas.gives major importance to the shape of the regulator molecule and the specificity of its "fit" onto some receptor within the plant. In this case, the benzene nucleus with its substituents acts as a whole at the locus or point of attachment, and chemical reactions at the ring are considered unlikely. The third and most recent theory, unlike the other two, is not concerned with the relations of the regulator with an "active site," but suggests that the growth-regulating activity of a compound is primarily associated with its ability to chelate metal ions, such as Mg++ (4).:'In order to make a comparative test of these theories, we have prepared the butyl ester of 5-chloro-2-pyrimidoxyacetic acid (Fig. 1, II) (5). This compound is almost identical with the very active growth regulator, butyl p-chlorophenoxyacetate ( Fig. 1, I) in its size, shape, ring planarity, molecular weight, halogen and ester reactivity, and also in those physical constants which were measured. However, the pyrimidine offers no possibility of nucleophilic reaction in the positions ortho to the ether oxygen (positions 1 and 3), and an aromatic type of substitution has never been observed to occur in positions 4 or 6 of the pyrimidine nucleus.The plant growth regulatory activity of compounds I and II ( Fig. 1) was measured by use of the oat coleoptile, wheat coleoptile, oat first-internode, and slit-pea curvature bioassays. In each case, the phenoxy ester was shown to be a highly active growth stimulator, while the pyrimidoxy est...

Feasible Synthesis of the GPR40 Antagonist by Constructing 2-Thiouracil Ring via Acid Mediated Cyclization

“…Thus, nucleophilic displacement of 1 afforded 2-ethoxy-5-bromopyrimidine 2 according to modification of literature procedures 7, 8 . Our method for preparation of 2 , using freshly prepared sodium ethoxide and absolute alcohol as solvent to improve the solubility of reactant, considerably improve the yield to over 95 %.…”

Potent and Selective ET-A Antagonists. 1. Syntheses and Structure−Activity Relationships ofN-(6-(2-(Aryloxy)ethoxy)-4-pyrimidinyl)sulfonamide Derivatives

“…2-Bromopyridine, 2-chloropyrimidine, 2-chloropyrazine, 3,6-dichloropyridazine, 4-chloro-2-methylthiopyrimidine, 2-bromothiazole, 2-bromoquinoline, 2-chloroquinoxaline, and 1-chloroisoquinoline were commercially available. 2-Chloro-5-methylpyrimidine, 17 2,5-dichloro-pyrimidine, 18 5-bromo-2-chloropyrimidine, 18,19 2-chloro-5-methoxypyrimidine, 20 2-chloro-4-methylpyrimidine, 21 2-chloro-4methoxypyrimidine, 22 and 2-chloro-5-methylthiopyrimidine 23,24 were prepared by the reported methods.…”

Potent and Selective ET-A Antagonists. 2. Discovery and Evaluation of Potent and Water Soluble N-(6-(2-(Aryloxy)ethoxy)-4-pyrimidinyl)sulfonamide Derivatives

“…2-Chloropyrimidine-5-carboxylic Acid. To a solution of 5-bromo-2-chloropyrimidine 11,12 (3.00 g, 15.5 mmol) in dry THF (200 mL) was added n-BuLi (1.63 M in hexane) (10.0 mL, 16.3 mmol) dropwise over 10 min at -90 °C, and the mixture was stirred at the same temperature for 15 min. The solution was poured onto solid carbon dioxide, and the whole was allowed to warm to -20 °C, acidified with 10% aqueous HCl, and extracted three times with CHCl3.…”

“…To a suspension of 60% NaH in mineral oil dispersion (81 mg, 2.01 mmol) in THF (2 mL) was added a solution of 13 (355 mg, 0.672 mmol) in dry DMAc (1 mL)-dry THF (5 mL) dropwise over 5 min at room temperature. 5-Bromo-2-chloropyrimidine 11,12 (195 mg, 1.01 mmol) was added. The mixture was stirred at room temperature for 2.5 h, diluted with ice-saturated aqueous NH4Cl, and extracted twice with EtOAc.…”

“…The residue was purified by silica gel column chromatography (CHCl3: MeOH, 100:1-10:1, v/v) to afford 2-(4-(N-(6-(2-hydroxyethoxy)-5-(4-methylphenyl)-4-pyrimidinyl)sulfamoyl)phenyl)-2-methylpropionic acid as pale yellow crystalline powder (1.28 (2) To a suspension of 60% NaH in mineral oil dispersion (344 mg, 8.59 mmol) in dry DMAc (3 mL)-dry THF (3 mL) was added the obtained hydroxyethoxy derivative (900 mg, 1.91 mmol) in dry DMAc (5 mL)-dry THF (5 mL) dropwise over 10 min at room temperature. 5-Bromo-2-chloropyrimidine 11,12 (1.48 g, 7.63 mmol) was added. The mixture was stirred at room temperature for 3 h, diluted with ice-10% aqueous HCl, and extracted twice with EtOAc.…”