Pyrimidine opening

These results show that inverse Diels-Alder reactions of pyrimidines open an easy access to a number of differently substituted pyridines and especially to compounds, in which the carbocyclic ring and the heterocyclic rings are annelated on the b position of pyridine. An interesting illustrating example... 

Unexpected products also arose from the reactions of 40 with excess (6-14 equivalents) hydroxylamine hydrochloride <99JHC787>. Unless R was very small (i.e., H or Me), this reaction provided the pyrimidine-opened 42 exclusively the oxime products 41 could not be isolated. With small substituents (i.e, R = H or Me), the normal oximes 41 were the sole product. 

Refluxing, 5.6-dihydro-7H-thiazolo[3,2-a]pyrimidine-7-one (370j with isopropylamine led to 2-imino-3-[2-(isopropylaminocarbonyl)ethyl]-thiazoline (371) (108). Similarly. tetrahydrobenzothiazolo[3,2-fl][2.3-f>]-quinazoline is opened by potassium hydroxide, yielding 373 (Scheme 214)... 

In recent years most examples of ring opening of this type have been noted in the pyrido[2,3-[Pg.207]

One or two cases are reported of a ring opening involving attack on a pyridinone ring in a 7-oxotetrahydropyrido[2,3-[Pg.209]

In aqueous alkaline conditions with chloroacetic acid the pyrido[4,3- f]pyrimidinethione (80) undergoes facile ring opening, attributed to the resonance stabilization of a delocalized covalent hydrate dianion intermediate (81) (82). Pyrido[2,3- f]pyrimidine-4-thiones (and... 

An unusual reaction involving s-triazine (247) and ethyl acetoacetate with sodium ethoxide leads eventually to the pyrido[4,3-ring opening and Dimroth-type rearrangement of the intermediate (248) (80JHC389>. 

Pyrazoles can be prepared by ring opening reactions of fused systems already containing the pyrazole nucleus. Thus several [5.5], [5.6] and [5.7] fused heterocycles have been opened to substituted pyrazoles, usually in basic medium. In general, the method has little preparative interest since another pyrazole derivative has usually been used to build the ring-fused system. However, due to the unexpected structures obtained, two publications are worthy of notice. 6//-Cyclopropa[5a,6a]pyrazolo[l,5-a]pyrimidine (638) was readily obtained from the corresponding pyrazolopyrimidine by the action of diazomethane at room temperature (Scheme 59) (81H(15)265). When (638) was treated with potassium hydroxide, the pyrazole (640) was formed, probably via the diazepine (639). 

Pyrido[2,3-d]pyrimidine-4-thiones ring opening, 3, 211 Pyrido[3,2-d]pyrimidinethiones reactions, 3, 211, 213 Pyrido[3,4-d]pyrimidinethiones reactions, 3, 211 Pyrido[4,3 -djpyrimidinethiones ring opening, 3, 211... 

The parent compounds undergo facile hydrolysis to aminoaldehydes subsequent to the covalent hydration and reversible ring-opening as described above for pyrido[4,3-d]pjrrimidines (Section IV, B). 2-(3-Pyridyl)pyTido[2,3-d]pyrimidine undergoes hydrolysis to yield 2-aminonicotinaldehyde and nicotinamide when treated with N—HCl under reflux for 3 hours. This mechanism also probably involves a covalent hydrate. 2-Methylpyrido[4,3-d]pyrimidin-4(3H)-one, although much more stable than the parent compound, is readily hydrolyzed with dilute acid, whereas the isomeric compounds from the other three systems are stable under such conditions. 

E. C. Taylor and his co-workers have demonstrated an important principle in the ring-opening of pyridopyrimidines and other fused pyrimidine systems to o-aminonitriles. They have demonstrated that based-catalyzed cleavage of a 4-substituted pyrimidine will occur provided that (a) the anion formed by the attack by the base at the 2-position can be stabilized by appropriate structural features in the remainder of the molecule and (b) that the substituent attached to the 4-position is capable of departure with its bonding pair of electrons in... 

Reactions of iV -alkylated or arylated azinium compounds with nucleophiles proceed more readily than those of the parent, uncation-ized azines, and the ring tends to open. The iV -substituent may bring into play an accelerative effect from the London forces of attraction. Increased displaceability of the substituent in iV -alkyl-azinium compounds has been noted for 2-halopyridinium (87) 1-haloisoquinolinium, 4-halopyrimidinium, 4-methoxypyrid-inium (88), 4-phenoxy- and 4-acetamido-quinazolinium (89), 3-methylthiopyridazinium, and 2-car boxymethylthiopyrimidi-nium salts (90). The latter was prepared in situ from the iV -alkyl-pyrimidine-2-thione. The activation can be effectively transmitted to... 

Triazanaphthalene (449) is the most unstable of the pyrido-pyrimidines to ring-degradation at pH 2 or pH 7.7 The 4-oxo derivative was converted into the 4-thioxo compound via nucleophilic displacement of the acyloxy intermediate formed with phosphorus pentasulfide. The 4-carboxymethylthio-pyridopyrimidine underwent some substitution by hydroxide ion but primarily gave the ring-opening reaction, which is facilitated by resonance activation of the 2-position by the 6-aza moiety. 

OKO-l,3,7-triazanaphthalene (450) forms acyloxy derivatives in situ with phosphorus oxychloride and pentasulfide which undergo nucleophilic displacement with chloride ion and with a complex sulfide ion, respectively, to form the 4-chloro and 4-thioxo derivatives. The 4-carboxymethylthio compoimd failed to undergo the ring-opening reaction (see below) characteristic of more activated azino- and diazino-pyrimidines, but it did yield about 10% of the 4-0X0 displacement product. 

Simple examples of diazoalkylideneamine-l,2,3-triazole equilibria have been demonstrated for a series of l,2,3-triazolo[l,5-a]pyrimidines by variable-temperature NMR [74JCS(CC)671]. Tautomers A, B, and C interconvert rapidly at elevated temperatures the energy barrier for these ring-opening-ring closure processes was found to be AG = 76 kJ mol (for = H, Me R = CONH2) (Scheme 111). 

Flash vacuum thermolysis (FVT) of 2-substituted 4//-pyrido[l,2-n]pyrimidin-4-ones 126 above 800 °C afforded (2-pyridyl)iminopropadie-none (130) (99JCS(P2)1087). These reactions were interpreted in terms of reversible ring opening of 4//-pyrido[l,2-n]pyrimidin-4-ones to imidoyl-ketenes 127. A 1,5-H shift in 127 generated the N(l)H-tautomeric methylene ketene 128, in which facile elimination of HX took place via a six-membered cyclic transition state 129 to yield 130. In the case of 2-methoxy derivative 126 (X = OMe) another competing pathway was also identified at lower temperature, which resulted in the formation C3O2 and 2-methylaminopyr-idine via mesoionic isomer 131 (Scheme 9). The products were identified by IR spectroscopy. 

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