L- -pyrimidinone

Oxodiperoxy(pyridine)(l,3-dimethyl-2,4,5,6-tetrahydro-2-l//> (pyrimidinone)molybdenum... 

As an extension of their work on the [4+ 4]-reaction of zirconacyclopentadienes and l,2-bis(bromomethyl)arenes (Section 10.13.2.4), Takahashi and co-workers reported a [5 + 4]-reaction based on the use of l,8-bis(bromomethyl)-naphthalene as the five-carbon component.85 As with the [4 + 4]-reaction, the [5 +4]-reaction works with a catalytic amount of CuCl, but higher yields and faster reactions result when stoichiometric CuCl and 1,3-dimethyl-3,4,5,6-tetrahydro-2(l//)-pyrimidinone(iV,iV -dimethylpropyleneurea) (DMPLJ) are used (Scheme 42). 

During initiation with metal ions, a solvent can play the role of a donor ligand to this metal ion and thus enforce its activity. An example from Smij chemistry is as follows In mixtures of HMPA and l,3-dimethyl-3,4,5,6-tetrahydro-2(l//)pyrimidinone with AN (but not with THF), the rate of reductive cyclization of o-allyloxyiodobenzene with Sml2 sharply increases (Hasegawa and Curran 1993). 

Palladium-catalyzed rearrangement of 2-allyloxypyrimidines gives A -allyl-2(l//)-pyrimidinones <1996CHEC-II(6)93>, but otherwise this approach has been little utilized. 

For the formation of 5-chloropyrimidines, AT-chlorosuccinimide is normally the reagent of choice, but several other electrophilic chlorine sources including chlorine gas or sulfuryl chloride can be used <1994HC(52)1>. For example, the chlorination of 4-(trifluoromethyl)-2(l//)-pyrimidinone 59 with ferric chloride and sulfuryl chloride in acetic acid gave the 5-chloro derivative 60 in 80% yield <2004EJ03714>. 

Hydrolysis of pyrimidinamines generally requires more vigorous conditions, although selective hydrolysis can often be achieved. Thus, the acid-catalyzed hydrolysis of 2,4,6-triaminopyrimidine 170 occurred in the 2-position to give 4,6-diamino-2(l//)-pyrimidinone 171 <2001JOC192>. Examples of selective diazotization of diamines are also known <2005JOC1612>. 

The pyrido[2,3-, pyrimidines 560 and 562 were prepared as analogues of the multitargeted antifolate (MTA) by the reaction of /3-keto ester 558 with either 2,4-diamino-6(l//)pyrimidinone 490 or 2,4,6-triaminopyrimidine 466, followed by saponification of the resulted glutamate products 559 and 561, respectively (Scheme 25) <1997H(45)2229>. 

After selective generation of the syn- or anH -enolate of an amide, it is usually reacted with a haloalkane, often the iodide. Allylic and benzylic bromides also react satisfactorily, and dimethyl and diethyl sulfate have also been used in some cases. A solution of the alkylating agent in an ethereal solvent, usually tetrahydrofuran, is added to the enolate, usually at low temperature. A polar, aprotic cosolvent, such as hexamethylphosphoric triamide, is frequently used as an additive in the alkylation step. The use of this suspected carcinogen is prohibited in some countries, which limits the usefulness of many of the reactions described below. However, similarly effective in many cases are some ureas, such as the commercially available 1,3-dimethyl-3,4,5,6-tetrahydro-2(l//)-pyrimidinone (DMPU)12. 

Yamaguchi, M., K. Wakasugi, R. Saito, Y. Adachi, Y. Yoshikawa, H. Sakurai, and A. Katoh. 2006. Syntheses of vanadyl and zinc(II) complexes of 1-hydroxy-4,5,6-sub-stituted 2(l//)-pyrimidinones and their insulin-mimetic activities. J. Inorg. Biochem. 100 260-9. 

In the photometric determination of copper, a coupling product formed between the diazonium salt from 2-amino-pyridine and resorcinol, or 4-(2-pyridinylazo)-l,3-benzenediol 21, has been used. Here the formed copper complex under acetate buffer exhibits an absorption peak at 520 nm, which is measured photometrically <2003KPU28>. Similarly for photometric determination of iron(ll), a coupling product formed between the diazonium salt of 2-amino-4,6-dihydroxypyrimidine and 8-hydroxyquinoline, or 6-hydroxy-2-(8-hydroxy-7-quinolinyl)azo-4(l//)-pyrimidinone 22, has been used. This reagent forms a blue complex with iron(n) ions with an absorption maximum at 625 nm that does not interfere with the presence of other metals <2003KD95>. 

Direct 5-fluorination can be effected on activated pyrimidines for example, F2 in HOAc or anhydrous HF can be used for the preparation of 5-fluoro-2(l//)-pyrimidinones <1977CCC2694>, and for 5,5-difluorination of 6-O-cyclouridines <1983TL1055>. Uracil and cytosine are 5-fluorinated by the same procedure <1980TL4605,... 

The 5,6-double bonds in activated pyrimidines such as 2-acylamino-6-acetyl-4(l//)-pyrimidinones 447 participate in DielsAlder reactions to yield, for example, hydroquinazolines 448 <1983JOC3627>. 

Cyclocondensation of asparagine with aromatic aldehydes gave 2-(substituted-phenyl)-6-carboxy-l,2,3,5,6-pcntahydro-4(l//)-pyrimidinones 55 <07MI2464>. A new approach to 3-alkyl(aryl)-2-thioxo-2,3-dihydro-1 //-benzofuro[3,2-c/]pyrimidin-4( I //)-oncs was developed,... 

Many years later, Davoll et al. reinvestigated the above experiments3,4 and ascribed the structure of 1-(2,3,4,6-tetra-0-acetyl-/9-D-glucopyranosyl)-4-methoxy-(or ethoxy-)2(l//)-pyrimidinone to the... 

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