Kosaku Hirota

Cycloaddition reaction of pyrimidine-dienols with dienophiles. A new approach to quinazolines

Abstract A new synthetic approach to quinazolines bearing a carboxy group is described. Reaction of 5-carbonyl substituted 1,3,6-tri-methyluracils (I) with dimethyl acetylenedicarboxylate or electron-deficient olefines affords quinazoline derivatives (III-VI) via pyrimidine(Z)-dienols (II) formed by base-catalyzed isomerization.

A novel ring transformation of 5-nitrouracils into 5-carbamoyluracils via the retro-michael reaction

Abstract Treatment of 1,3-disubstituted 5-nitrouracils (5) with malonamide in ethanolic sodium ethoxide caused a ring transformation to afford 1-substituted 5-carbamoyluracils (6) in good yields.

A synthesis of ψ-cytidine

Abstract A practical, seven-step synthesis of 5-(β- d -ribofuranosyl)cytosine ( 1 , ψ-cytidine) was achieved. ψ-Uridine was converted into the 2′,3′-isopropylidene acetal 2 in 85% yield. Tosylation of 2 to the 5′-sulfonate 3 , followed by deacetonation, afforded 5′- O -tosyl-ψ-uridine ( 6 ) in good yield. Treatment of 6 with 1,1′-carbonyldiimidazole afforded the 2′,3′-cyclic carbonate 10 , which was converted into 4,5′-anhydro-2′,3′- O -carbonyl-ψ-uridine ( 11 ) by treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in N , N -dimethylformamide. 4,5′-Anhydro-ψ-uridine ( 7 ) was obtained in quantitative yield from 11 by decarbonylation in aqueous pyridine. Ammonolysis of 7 afforded ψ-cytidine ( 1 ) in good yield.

Novel C–C bond formation at the 5-position of uracils. Facile synthesis of 5-methoxycarbonylmethyluridine and 5-carbamoylmethyluridine, minor component nucleosides derived from transfer ribonuclease

5-Hydroxyuracil derivatives were treated with stable Wittig reagents to give the corresponding 5-alkyluracil derivatives such as 5-methoxycarbonylmethyl-uridine and 5-carbamoylmethyluridine.

Pyrimidine derivatives and related compounds. Part 42. Isolation of the intermediates in the ring transformation of 1,3-oxazine-2,4-diones into pyrimidines and pyrazoles, and their structure determination by 15N nuclear magnetic resonance analysis

Reaction of the 6-methyl-1,3-oxazine-2,4-diones (1) and (2) with hydrazine hydrate at room temperature gave the 6-hydroxy-5,6-dihydrouracils (7a) and (8a). The structures of the products were determined by 15N n.m.r. analysis. The mechanism of the ring transformation of 1,3-oxazines into pyrimidines and pyrazoles is discussed.

Pyrimidine derivatives and related compounds. Part 37. Novel nucleophilic substitutions of 5-bromo-6-methyluracils or 5-bromo-6-bromomethyluracils with aromatic amines

Condensation of 1-substituted or 1,3-disubstituted 5-bromo-6-methyluracils (4) and aromatic amines gave the corresponding 6-arylaminomethyluracil derivatives (5). Treatment of 5-bromo-6-bromomethyl-1,3-dimethyluracil (10) with primary aromatic amines gave the corresponding 6-arylidenemethyluracil derivatives (11). Reaction of (10) with N-methylaniline gave 5-bromo-1,3-dimethyl-6-(N-methylanilino)methyluracil (13a), which was further treated with primary aromatic amines to afford (11).

Pyrimidine derivatives and related compounds. Part 36. Nucleophilic addition reaction of a cyanide lon to 6-substituted 1,3-dimethyl-5-nitrouracils. Synthesis of 5,6-dihydrouracil and 5,6-dihydrocyclo-thymine derivatives

6-Substituted 1,3-dimethyl-5-nitrouracils (3a–c) react with potassium cyanide to give stereospecifically the 6-cyano-5-nitro-5,6-dihydrouracils (4a–c). Reaction of 6-bromomethyl-1,3-dimethyl-5-nitrouracil (7) with potassium cyanide gives 6-cyano-1,3-dimethyl-5-nitro-5,6-dihydrocyclothymine (8). The structures of the 5,6-dihydrouracils (4a–c) and the cyclothymine (8) were clarified using 1H and 13C n.m.r. spectroscopy.

Pyrimidine derivatives and related compounds. Part 41. Reactions of 1,3,6-trimethyl-5-nitrouracil and its 6-bromomethyl analogue with amines and hydrazines. Synthesis of pyrazolo[4,3-d]pyrimidine N-oxides and their ring expansion to pyrimido[5,4-d]pyrimidines

Reactions of 1,3,6-trimethyl-5-nitrouracil (1) and 6-bromomethyl-1,3-dimethyl-5-nitrouracil (4) with amines and hydrazines have been studied with the aim of synthesising fused-ring pyrimidines. Treatment of compound (4) with primary amines afforded 2-substituted pyrazolo[4.3-d]pyrimidine 1-oxides (6a–I). Of these, compounds (6h–I) were converted into pyrimido[5,4-d]pyrimidines (11) by treatment with sodium ethoxide. Although treatment of compound (1) with hydrazines caused the known ring transformation giving pyrazolones (2a and b), a new type of denitration reaction was found when compound (4) reacted with hydrazines yielding 6-hydrazonomethyl-1,3-dimethyluracils (15a and b). Treatment of the 6-(substituted methyl)-1,3-dimethyl-5-nitrouracils (13b–d) and (14)[prepared from (4)] with hydrazines also gave (15a and b). Mechanisms for the formation of compounds (6), (11), and (15) are discussed.

Studies on the Uracil Herbicides

ウラシル系除草剤S-113およびS-114の作用特性を検討した。1. 温室内の播種直後土壌処理では, S-113およびS-114いずれもマメ科作物に対して, bromacil に比べて著しく作用は小さい。ヒエおよびコマツナとマメ科作物との選択殺草性の順位は, S-113の場合はエンドウ=アズキ>ダイズ>インゲンの順であった。また, S-114ではエンドウ>アズキ>ダイズ>インゲンの順であった。2. 生育期茎葉処理でも bromacil より作用は著しく小さく, 同様に選択殺草性の順位は, S-113の場合はエンドウ>インゲン>アズキ≧ダイズの順であり、S-114ではエンドウ=インゲン=ダイズ>アズキの順であった。3. S-113およびS-114の最適処理時期を検討した結果, 選択殺草性からみて, 播種直後土壌処理が最も適切であると判断された。4. 圃場試験では, S-113の場合a当たり5gの播種直後土壌処理でラッカセイ, ダイズ, アズキならばにエンドウに対し適用性が認められた。またS-114では, 同薬量でエンドウに適用性が認められた。5. 土壌水分と作用力との関係は, 含水量が大になるほどヒエ殺草力は増大したが, 通常のマメ科作物畑での含水量65～75%では, S-113およびS-114いずれも高い選択殺草性を発現することが判明した。6. 土壌中での移行性は, 埴壌土では bromacil>S-113≧S-114の順であり, 砂壌土では bromacil>S-113=S-114の順であった。7. 土壌中での残効性は, 半減期がS-113およびS-114いずれも埴壌土で90日, 砂壌土で70～80日であった。土壌中ではきわめて安定な化合物であることが判明した。