4- Aminopyrimidine, conversion

Aminopyrimidine [591-55-9] M 95.1, m 171-172 (with sublimation), pK 2.52. Purified by conversion to the MgCl2 complex in a small vol of H2O. The complex ( 5g) is dissolved in the minimum vol of hot H2O, passed through a column of activated AI2O3 (200g) and the column washed with EtOH. Evapn of the EtOH gives a colorless residue of the aminopyrimidine which is recrystd from CgH6 (toluene could also be used) which forms needles at first then prisms. It melts with sublimation. Acetylation yields 5-acetamidopyrimidine which crysts from C H6, m 148-149°. [Whittaker 7 CAem Soc 1565 1951.]... 

A related agent, g1 icetanile sodium (42), is made b / a variant of this process. Methyl phenyl acetate is reacted with chlorosulfonic acid to give 38, which itself readily reacts with aminopyrimidine derivative 39 to give sulfonamide Saponification to acid 4 is followed by conversion to the acid chloride and amide formation with 5-chloro-2-methoxyaniline to complete the synthesis of the hypoglycemic agent glicetanile (42). ... 

The diazotization of amino derivatives of six-membered heteroaromatic ring systems, particularly that of aminopyridines and aminopyridine oxides, was studied in detail by Kalatzis and coworkers. Diazotization of 3-aminopyridine and its derivatives is similar to that of aromatic amines because of the formation of rather stable diazonium ions. 2- and 4-aminopyridines were considered to resist diazotization or to form mainly the corresponding hydroxy compounds. However, Kalatzis (1967 a) showed that true diazotization of these compounds proceeds in a similar way to that of the aromatic amines in 0,5-4.0 m hydrochloric, sulfuric, or perchloric acid, by mixing the solutions with aqueous sodium nitrite at 0 °C. However, the rapidly formed diazonium ion is hydrolyzed very easily within a few minutes (hydroxy-de-diazonia-tion). The diazonium ion must be used immediately after formation, e. g., for a diazo coupling reaction, or must be stabilized as the diazoate by prompt neutralization (after 45 s) to pH 10-11 with sodium hydroxide-borax buffer. All isomeric aminopyridine-1-oxides can be diazotized in the usual way (Kalatzis and Mastrokalos, 1977). The diazotization of 5-aminopyrimidines results in a complex ring opening and conversion into other heterocyclic systems (see Nemeryuk et al., 1985). 

The Dimroth rearrangement has been utilized for the conversion of (108) to the 2,N-polymethylene-bridged 6-aminopyrimidine (109) (75AJC119). Photochemical rearrangements of isoxazolophanes (110) into oxazolophanes (111) have been demonstrated to go through an azirine intermediate (112) (79TL1875). Chemical modification of these... 

The most important route is the conversion of pyrimidines into 1,3,5-triazines. The first one-step transformation was effected by Taylor and Jefford (62JA3744) by heating the pyrimidine (179) with benzenesulfonyl chloride in pyridine (equation 106). The reaction may be considered as an example of an abnormal Beckmann rearrangement. The mechanism of the reaction of the 4-aminopyrimidine (180) is probably dependent on the nature of the 2-substituent (180, R). If R is an electron-releasing moiety, pathway B seems more likely (Scheme 109). The 4-hydroxypyrimidine (179 R = OH) behaves similarly. Many 2-cyano-1,3,5-triazines may be synthesized by this method. 

A diazabicyclohexadiene (145), however, is considered to be an intermediate in the photochemical conversion of 2,6-dimethyl-4-aminopyrimidine (146) into the nitrile (147).134... 

Conversion of diazonium halides into chloropyrimidines has employed excess chloride ion or copper(I) chloride. These reactions have been mainly used to make 2- and 4-chloropyrimidines although the 5-chloro derivatives are also available in this way. One drawback is the substantial amount of oxo product formed, especially when 2-aminopyrimidines are... 

It must, nonetheless, be emphasized that the products of reduction of pyrimidine have not been unequivocally identified, largely due to their instability in the presence of air (oxygen). Furthermore, the UV absorption spectra of the reduction products of waves I and II (kmax284 nm, smax 1.5 x 103) are suggestive of rapid conversion (proton-catalyzed hydration ) of the products, since both the dimer and the dihydro derivative possess a reduced system of aromatic bonds relative to the parent pyrimidine, as a result of which the UV absorption maximum should be shifted to the violet, whereas it is, in fact, shifted 44 nm to the red (from 240 nm to 284 nm) for both products. Of possible relevance to this is the fact that the reduced rings of 4-aminopyrimidine 102) and nicotinamide 103) undergo acidic hydration to form products absorbing at 280 to 290 nm. 

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