Studies of the New Herbicide KIH-6127. Part II. Synthesis and Herbicidal Activity of 6-Acyl Pyrimidin-2-yl Salicylates and Analogues against Barnyard Grass

Abstract

The method reported previously (Part I) was employed to prepare a variety of novel 6-acylsalicylates as key intermediates. 6-Acylpyrimidin-2-yl salicylates (2-acyl-6-[(4,6-disubstituted pyrimidin-2-y1)oxylbenzoate derivatives: Type l), the closely related phthalide compounds (3-alkyl-7-[(4,6-dimethoxypyrimidin-2-yl)oxy]phthalide derivatives : Type 2) and the ketal derivatives of 2-acyl-6-[(4,6-dimethoxypyrimidin-2-yl)oxy]benzoates (Type 3) were synthesized and their herbicidal activities measured. Methyl 2-acetyl-6-[(4,6-dimethoxypyrimidin-2-yl)oxy]benzoate gave excellent control of barnyard grass with a promising profile as a prototype rice herbicide.

7‐(4,6‐Dimethoxypyrimidinyl)oxy‐ and ‐thiophthalides as novel herbicides: Part 1. CGA 279 233: a new grass‐killer for rice

“…We observed that, in general, all the ketal esters II , IIb , IIc and IA (R 4 = OR) are far less sensitive to acid‐ or base‐catalysed hydrolysis than the corresponding ortho ‐acetyl salicylates IX, IXa and their 6‐acyl‐pyrimidin‐2‐ylthiosalicylate derivatives A ′ that can undergo self‐catalysed rearrangement merely on standing to give the corresponding phthalide forms II , IIb , IIc and IA (R 4 = alkoxy) 8. 9, 27 The 6‐acylsalicylic acids IX (R = H) and the free acid derivatives A ′ (Figs 1 and 3; R = H) are generally isolated as the corresponding 3‐hydroxyphthalide forms IVb , IVc , II (R 4 = OH) and IA (R 4 = OH), as was shown by Finkelstein et al 29 for 3,7‐dihydroxy‐3‐methylphthalide II (R 3 = Me, R 4 = OH).…”

“…These were then coupled with the pyrimidines IIIa at moderate temperatures (45–65 °C) to give the pyrimidinylmercaptophthalides IA (Figs 1 and 4; X = S, R 1 = R 2 = OMe), for example CGA 279 233 ( 37 ) and its 3‐hydroxy analogue 42 . The 3‐hydroxyphthalides IA (X = S, R 4 = OH), such as 42 , could then be transformed into further phthalide compounds IA (R 4 ≠ OH), such as 37, 43–47 , or into the alkylidenephthalides IB (X = S), or into known or still novel compounds of the type A ′ (X = S)7, 9, 32 (Figs 1, 4 and Table 1). The compounds IA (X = S) may be oxidized into the corresponding sulfoxides or sulfones IA (X = S(O), S(O) 2 ) 33…”

“…Following known procedures, the 2‐acetyl‐6‐nitrobenzoic acid ( XIX ) was first reduced to 7‐amino‐3‐hydroxy‐3‐methylphthalide ( XXb ; 5% Pd/C or Na 2 S),40 which was then diazotized by adding, at room temperature, the diazonium salt of XXb to a freshly prepared alkaline solution of sodium disulfide (Na 2 S 2 ), to give the 3‐hydroxy‐7‐mercapto‐3‐methylphthalide ( Xb ; Fig 7). 7, 9 Under these reaction conditions Xb was obtained together with larger amounts of its disulfide Xb ′. The latter was then (if not required for other purposes, as for example for the synthesis of 42 , Fig 4) directly reduced with sodium borohydride to the desired 7‐mercapto‐3‐methylphthalide ( Xc ).…”

“…7‐(4,6‐Dimethoxypyrimidin‐2‐yl)thio‐3‐hydroxy‐3‐methylphthalide ( 42 ; 35.1 g, 0.1 mol) was alkylated as in Section 2.2.19 using a mixture of dimethyl sulfate (10.5 ml, 0.11 mol) and acetone (200 ml) in the presence of potassium carbonate (17.4 g, 0.13 mol), yielding, after crystallisation from dichloromethane and hexane, product A ′ 2 ( A ′; X = S, R 3 = R = Me); yield 32.5 g, 89% m p : 125–126 °C (Literature9 149–151 °C). [ 1 H]NMR (CDCl 3 ): 7.93 (d 1H); 7.88 (d, 1H); 7.53 (t, 1H); 5.73 (s, 1H); 3.92 (s, 3H); 3.72 (s, 6H); 2.62 (s, 3H).…”

“…A class of novel (4,6‐dimethoxypyrimidin‐2‐yl)oxysalicylates1–3 and their corresponding thiosalicylic acid analogues4 of the general structure A (Fig 1)5 were reported by Kumiai, leading to the development of KIH‐2031 (Q = Cl, X = S, R = Na) for use in cotton,6 KIH‐2023 (Q = 2‐(4,6‐dimethoxypyrimindinyl)oxy, X = O, R = Na)3 and later of KIH‐6127 (Q = C(Me)NOMe, X = O, R = Me),7, 8 a pro‐pesticidal oxime‐ether derivative of the acyl compound A ′ (X = O, R 3 = R = Me),7–9 for use in rice. Common to this new class of highly active (4,6‐dimethoxypyrimidinyl)oxybenzoate and ‐thiobenzoate herbicides is the existence of an easily hydrolysable carboxylic ester function COOR in the ortho ‐position to the 4,6‐dimethoxypyrimidinyl moiety.…”