3‐Methylthio‐5‐trifluormethyl‐1,2,4‐triazin als Edukt zur Synthese heteroanellierter Pyridine durch intramolekulare Diels‐Alder‐Cycloaddition mit inversem Elektronenbedarf

Abstract

Wir beschreiben eine Synthese von 3-Methylthio-5-trifluormethyl-1,2,4-triazin (4) aus Trifluorpyruvaldehyd (2) und S-Methyl-thiosemicarbazid. Nuclwphile Substitution der Thiomethylfunktion durch die Alkoxide von 6a-c, 11 und 14 bzw. durch die @Amino-1-aUdne 17a-c fuhrt zu den Triazinen 7, 12 und 15 bzw. 18, die u k r eine Sauerstoff-oder NH-Briicke mit dern Seitenkettendienophil verknupft sind. Diese Ragieren beim Erhitzen in Chlorbzw. Nitrobenzol glatt zu den neuen heteroanellierten Pyridinen 8-10,13,16, 19-21. 3-Methylthio-5-trifluoromethyl-l,2,4-b'iazine as Starting Material for the Synthesis of Hetero-Annulaled Pyridines via Intramolecular DielsAlder-Cycloaddition with Inverse Electron DemandWe describe a synthesis of 3-methylthio-5-trifluoromethyl-1,2,4-triazine (4) using trifluoropyruvaldehyde (2) and S-methylthiosemicarbazide as starting materials. Nucleophilic displacement of the thiomethylgroup in 4 by the alkoxides of 6a-c, 11 and 14, or with the @amino-1-alkynes 17ac leads to the triazines 7,12 and 15 or 18 with oxygen-or nitrogen-linked side chains. On heating in chloro-or nitrobenzene these undergo remarkably facile intramolecular Diels-Alder-reactions to yield the novel hetero-annulated pyridines 8-

Diels–Alder Reaction in the Synthesis of Fluorinated (Hetero)Aromatic Compounds

“…Additional examples were published by John and Seitz, who synthesized triazine 99 from trifluorodibromoacetone in two steps and reacted it with ω‐hydroxyalkynes giving products 100 . These triazines underwent intramolecular Diels–Alder reactions to yield fused pyridines 101 on heating.…”

Fluorinated Triazines

“…The synthesis of 3-methylthio-6-trifl uoromethyl-1,2,4-triazine 31 was achieved by using trifl uoropyruvaldehyde 28 and S-methylthiosemicarbazide 27 as starting materials (Scheme 15 ) [ 24 ]. 3-Aminotriazine 33 was prepared by the condensation of aminoguanidine 32 with dibromoketone 29 , this condensation was non-selective, and 6-trifl uoromethyl-isomer as by-product was formed (Scheme 15 ) [ 25 ].…”

Novel [3+2] and [3+3] 4-quinolone annulations by tandem Claisen-Cope amidoalkylation reaction

“…4-(Allyloxy)quinolines 11 and 13 and 4-(propargyloxy)quinoline 12 were prepared as substrates for the tandem Claisen-Cope rearrangement as shown in Scheme . The chloroimidate derived from treatment of 3,4-difluoroacetanilide (8) with PCI5 was condensed with diethyl sodiomalonate to give an intermediate enamino diester, which was cyclized thermally in Dowtherm to afford a regioisomeric mixture of difluoroquinolones 9 and 10, with the desired 6,7-difluoro isomer 9 predominating by «3.3:1. Alkylation of the mixture of 9 and 10 under standard conditions with allyl bromide, propargyl bromide, and (/S-chloromethyl)allyl chloride, respectively, provided quinolines 11-13.…”

“…The toluene layer was separated, and the aqueous layer was extracted with EtOAc (4 X 200 mL). The EtOAc extracts were combined with the original toluene layer and were washed with brine, dried (11) Finger, G. C.; Kruse, C. W. J. Am.…”

“…6.7-Difluoro-2-methyl-4-(2-propenyloxy)-3-quinolinecarboxylic Acid Ethyl Ester (11). Alkylating agent, allyl bromide: yield 52%; mp 51-53 °C; R¡ = 0.6,1:1 EtOAc-hexanes;…”