Amination of pyrimidines

These pyridazines are subject to direct deactivation of the leaving group. It would appear from the conditions used in its reactions with ammonia (115°) and methylamine (50°) that 4-chloro-2-ethylthiopyrimidine (225) is somewhat deactivated (indirect). In various aminations of pyrimidines, the effect of an alkylthio group seems to be very mildly deactivating, like that of methyl groups. However, these surmises from the conditions used are not as reliable as the direct qualitative comparison described above and the kinetic data. 

Unfortunately, the two fuU papers on the silylation-amination of pyrimidine [49] and purine nucleosides [64] as discussed in Sections 4.2.3 and 4.2.4, were pubhshed in German and are thus not readily accessible, although a few detailed procedures from Sections 4.2.3 and 4.2.4 were subsequently published in English [65]. The third paper on the silylation-amination of aromatic hydroxy-N-hetero-cycles, however, as discussed in Section 4.2.5 was, fortunately, pubhshed in English [27]. 

While aminations of pyrimidines typically exploit SnAt substitutions, direct lithiation of pyrmidine derivatives 45 with LDA or sec-BuLi, and in situ quenching with the nitroso electrophile MNP led to the formation of the new C-N bond in the products 46 <01JOC3513>. These hydroxyl amines were subsequently oxidized to aminoxyl radical spin labels. Analogous chemistry on purine nucleosides was also reported. 

It has been established by experimental data that the Chichibabin amination of pyrimidine proceeds either by an Sn(AE) or Sn(ANRORC) mechanism. Each mechanism is favored according to substituents, substitution pattern and reaction conditions. In turn, the region-chemical outcome for the reaction depends on the mechanism course the reaction follows. 2-bromo-4-phenylpyrimidine (21) reaction with KNH2-NH3... 

Alkylation of pyrimidin-2(or 4)-amine on a ring-nitrogen gives an imine, e.g. (8), of quite high basic strength (pjSTa 10.7) because its cation, e.g. (13 R = Me), has typical and effective resonance stabilization indeed, methylation of pyrimidine-2,4-diamine gives a still stronger base (pjSTa> 13) due to an even more resonance-stabilized cation (14). 

The aminolysis of esters of pyrimidine occurs normally to yield amides. The reagent is commonly alcoholic ammonia or alcoholic amine, usually at room temperature for 20-24 hours, but occasionally under refiux aqueous amine or even undiluted amine are used sometimes. The process is exemplified in the conversion of methyl pyrimidine-5-carboxylate (193 R = Me) or its 4-isomer by methanolic ammonia at 25 °C into the amide (196) or pyrimidine-4-carboxamide, respectively (60MI21300), and in the butylaminolysis of butyl ttracil-6-carboxylate (butyl orotate) by ethanolic butylamine to give A-butyluracil-5-carboxamide (187) (60JOC1950). Hydrazides are made similarly from esters with ethanolic hydrazine hydrate. 

Primary synthesis of arylazopyrimidines is used (52JCS3448). It is exemplified in the condensation of phenylazomalondiamidine with diethyl oxalate to give the azopyrimidine (833) (66JCS(C)226). Finally, 5-phenylazopyrimidine may be made by the condensation of pyrimidin-5-amine with nitrosobenzene (5UCS1565) but the reaction seems to have been overlooked for many years. 

The first pyrimidine analogues of sulfanilamide were introduced in 1942, some five years after the start of the bacterial chemotherapy revolution. Sulfadiazine (1018 R = R = H) and sulfamerazine (1018 R = Me, R = H) may be made by treatment of pyrimidin-2-amine or its 4-methyl derivative, either with p-acetamidobenzenesulfonyl chloride followed by... 

Note Traces of ammonia left by the mobile phase should be completely removed from the chromatograms before the reagent is applied in order to avoid strong background coloration. The dipping solutions may also be applied as spray solutions. Secondary amines, amides, pyrimidines and purines do not react with the reagent [1]. In the case of benzodiazepines only those substances react which... 

Alkylthio, arylthio, and thioxo. The thioxo group in pyrimidine-2,4-dithione can be displaced by amines, ammonia, and amine acetates, and this amination is specific for the 4-position in pyrimidines and quinazolines. 2-Substitution fails even when a 5-substituent (cf. 134) sterically prevents reaction of a secondary amine at the 4-position. Acid hydrolysis of pyrimidine-2,4-dithione is selective at the 4-position. 2-Amination of 2-thiobarbituric acid and its /S-methyl derivative has been reported. Under more basic conditions, anionization of thioxo compounds decreases the reactivity 2-thiouracil is less reactive toward hot alkali than is the iS-methyl analog. Hydrazine has been reported to replace (95°, 6 hr, 65% 3deld) the 2-thioxo group in 5-hexyl-6-methyl-2-thiouracil. Ortho and para mercapto- or thio- azines are actually in the thione form. ... 

Sulfonate and sulfamoyl. A nitrile group is introduced into the 3- or 4-position of pyridine and into the 2- or 4-position of pyrimidine by displacement of a sulfonate group with potassium cyanide. Amines, water, or hydrazine displace 2- or 4-sulfonate groups from pyridine derivatives. 4-Quinolinylsulfonates (139)... 

The catalytic effect of protons, of bifunctional catalysts, and of base is demonstrated in the amination of chloro derivatives of pyridazine, pyrimidine, and s-triazine (Tables V and VI). Anilino-s-triazines containing NH groups act as catalysts in their own formation. The catalytic action of protons on anhino-dechlorination of 2-chloro-4,6-diamino-s-triazine and of 2-amino-4-chloropyrimidine was reported in the classic paper by Banks. ... 

After silylation-amination in situ transsilylation (cf Section 2.3) of the intermediate persilylated cytidines 5 with excess boiling methanol for 3-5 h gives the desired free cytidines 6 and methoxytrimethylsilane 13a (b.p. 57°C) [13]. Thus protection of the alcohohc hydroxyl groups of the ribose moiety and silylation-activation of the 4-position in the pyrimidine moiety in persilylated uridine 3, and the concomitant amination of 3, aU in one reaction step, to 5 is followed finally by in situ transsilylation (cf. Section 2.3) with excess boihng methanol in one reaction vessel. 

The advantages of the one-step silylation-amination of hydroxy-N-heterocycles are demonstrated by the amination of 2-methylpyrido[3,4-d]pyrimidin-4-one 261. Whereas silylation-amination of 261 with three equivalents of benzylamine-... 

Analogous photoadditions have been observed on irradiation of pyrimidine and purine bases in ethers and amines. Irradiation of 1,3-dimethylur-acil (314) in tetrahydrofuran leads to the formation of 5- and 6-(tetrahydro-furan-2-yl)-5,6-dihydrouracils 315 and 316.261 Similarly, solvent adducts arising by way of initial hydrogen abstraction have been obtained on irradiation of pyrazine derivatives in diethyl ether or tetrahydrofuran.262 The... 

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