6-Chloro-l,3-dimethyluracil

A kind of modification of the Polonovski-Boon synthesis is the reaction of 5,6-dihalopyrimidines with ethylenediamine derivatives. Depending on the bulkiness of the amino substituents a more or less regiospecific condensation may proceed (71CB780), as shown recently in the reaction of 5-bromo-6-chloro-l,3-dimethyluracil (279) with 2-methyl-amino- -propylamine to form l,3,5,6-tetramethyl-5,6,7,8-tetrahydrolumazine (280 equation 99) (80Ba3385). 

Photolysis of 6-chloro-l,3-dimethyluracil (150) with the 1,3,4-oxadiazole 151 afforded the pyrazolo[3,4-d]pyrimidine 152, with photoelimination of benzoyl chloride (80CB2566). 

Irradiation in water usually produces 5,6-hydrated compounds whereas in D20 dimers are the main products. 6-Chloro-l,3-dimethyluracil yields the cis-syn dimer (72) <69TL22ll>. 

Chloro-l,3-dimethyluracil (64JHC212) is a convenient compound for synthesizing fused uracils. Thus, 1,3,6-trimethyllumazine is prepared by reaction of 6-chloro-5-nitrouracil with 2,2-ethylenedioxypropylamine followed by catalytic reduction (67JHC124). 

Chloro-l,3-dimethyluracil undergoes 1,2-Addition to benzene on irradiation. A 1,3-addition path has been discounted. Other studies by the same group have demonstrated that the irradiation of the pyrimidine dione derivative (140) in acidic media (a large excess of trifluoroacetic acid) brings about its conversion into the tricyclic product (141). ... 

Imidazole ring formation of acyclo C-nucleoside 543 was made by reaction of 6-chloro-l,3-dimethyl-5-nitrouracil with o-glucopyranosylamine (541), followed by catalytic hydrogenation and concomitant cyclization of 542 (67CB492). The same C-nucleoside (543) was obtained by reacting 1-amino-l-deoxy-D-glucitol (544) with 6-chloro-l,3-dimethyluracil and subsequent nitrosation and cyclization (96S459) (Scheme 145). 

Fe(III) salts catalyse the coupling of Grignard reagents with alkenyl and aryl halides. The mechanism is not fully understood, but probably resembles the standard palladium sequence, through either an Fe(0)-Fe(II) or an Fe(I)-Fe(III) cycle. A particular feature is that chlorides are superior, in terms of yield, to bromides and iodides as substrates. Triflates also give very high yields and couple selectively in the presence of chlorides. Heterocyclic examples include 6-chloropurines, 4-chloropyrimidines, 6-chloro-l,3-dimethyluracil and 2-chloropyridines," and the dichloropyridine example below." ... 

Of preparative importance are the following methods the first, and most simple is based upon intramolecular alkylation of 8-(3-chloropropyl)purine intermediate 18b in dilute alkali. The key intermediate 18b was obtained by a four-step synthesis starting from 6-chloro-l,3-dimethyluracil and 4-(hydroxybutyl-amino)-5-nitrosouracil 16b, its cyclodehydration to 8-(3-hydroxypropyl)-purinedione 18a and reaction with thionyl chloride (85JHC105) (Scheme 5). 

This acid-catalyzed photoreaction has successfully been applied to 6-chloro-l,3-dimethyluracil (6-CIDMU). 

TABLE 105.1 Photolysis of 6-Chloro-l,3-dimethyluracil in Benzene in the Presence of Various Acids... 

Ohkura, K., Kanazashi, N., and Seki, K., Synthesis of cyclooctapyrimidine-2,4-diones by photocycloaddition of 6-chloro-l,3-dimethyluracil to benzenes in the presence of trifluoroacetic acid, Chem. Pharm. Bull, 41, 239, 1993. 

Ohkura, K., Noguchi, Y., and Seki, K., Acid-catalyzed photoreaction of 6-chloro-l,3-dimethyluracil in frozen benzene formation of novel cycloadducts, tetrahydropentaleno[l,2-e]pyrimidine-2,4-dione derivatives, Chem. Lett., 99,1997. 

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