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Treatment of 4,5-diaminopyrimidine-2-thione (1) with freshly prepared triethyl orthopropionate–propionic anhydride gives not only the expected 8-ethylpurine-2-thione (2; R = Et) but also 8-ethyl-2-ethylthiopurine (3; R1= SEt. R2= Et). In the latter, the S- and 8-substituents are derived respectively from the alcoholic and acyl portions of the orthoester. The ratio of products depends on conditions. The same mixed reagents also cause S-ethylation of preformed purine-2(or 8)-thiones. Similar treatment of 2-thiouracil gives a separable mixture of its S- and N(1)-ethyl derivatives; 4-thiouracil yields the S- and N(3)-ethyl isomers.

4,5-Diaminopyrimidines are converted by boiling tetraethoxy-, tetrapropoxy-, and tetrakismethylthio-methane into the corresponding 8-alkoxy- or 8-methylthio-purines. By conducting the first stage of the reaction at 25° in the presence of acetic acid, the intermediate diethoxymethyleneaminopyrimidines (3) may be isolated prior to thermal cyclization. 5,6-Diaminopyrimidine-2(and 4)-thiones normally undergo S-alkylation by the orthocarbonate as well as cyclization but, under acidic conditions, the 4-thiones yield 2-alkoxy-7-aminothiazolo[5,4-d]pyrimidines (4) instead of purines. Treatment of o-phenylenediamine, 2,3-diaminonaphthalene, and 2,3-diaminopyridine with a tetra-alkoxymethane gives the appropriate 2-alkoxylated benzimidazole (5; X = CH), naphth[2,3-d]imidazole (6), or imidazo[4,5-b]pyridine (5; X = N). Ionization constants, u.v. absorption, and 1H n.m.r. data are recorded and discussed.

o-Aminobenzonitrile is converted by triethyl orthoformate–acetic anhydride into its N-ethoxymethylene derivative (2), which can undergo alkylaminolysis followed by spontaneous cyclization to 3-alkyl-3,4-dihydro-4-iminoquinazolines (3; X = CH); these rearrange in alkali to 4-alkylaminoquinazolines. The related 3,4-dihydro-4-imino-2,3-polymethylenequinazolines (8; X = NH) are also prepared from o-aminobenzonitrile, either by condensation with appropriate cyclic imino-ethers or by cyclodehydration with lactams; when the 2,3-polymethylene chain is longer than five CH2 units, Dimroth rearrangement occurs in alkali to give the isomeric β-bridged 2,N(4)-polymethylene-4-aminoquinazolines (9; X = CH). Aza-analogues of the above systems are prepared by analogous routes. Rates of rearrangement are discussed.

A new primary synthesis of 1,6-dihydro-6-imino-1-methylpyrimidine (3a) and its 2-,4-, and/or 5-alkylated derivatives (3c–o) is described: a 3-aminoacrylonitrile (1) is converted by an orthoester into its 3-ethoxyalkylidene-amino-analogue (2) which undergoes methylaminolysis and subsequent cyclization to the required imine (3); a similar route gives the bicyclic imines (6; n= 3 or 4). All the imines rearrange in alkaline media to the corresponding 6(4)-methylaminopyrimidines [(4) or (7)], but at widely differing rates which depend on the position, type, and number of C-alkyl substituents. The rearrangement rates, ionization constants, and some mass spectra are discussed.

2-Fluoropyrimidine and its 4-methyl and 4,6-dimethyl derivatives are made by diazotization of the corresponding aminopyrimidines in fluoroboric acid. 4-Fluoro-2-methylpyrimidine, its 6-methyl isomer, and 4-fluoro-2,6-di-methylpyrimidine result from treatment of appropriate trimethylpyrimidin-4-ylammonium chlorides with aqueous potassium hydrogen difluoride. Second-order rate constants for piperidinolyses of the fluoropyrimidines and of 2-bromo-, 2-iodo-, 4-chloro-5-methyl-pyrimidine indicate that the fluoropyrimidines react 60–200 times faster than other (corresponding) halogenopyrimidines at the same temperature. The u.v. and 1H n.m.r. spectra are recorded and discussed.

In view of the high amplifying activity shown by 6,9-dimethyl-2-methylthiopurine (1 : R = SMe), a number of analogues have been synthesised. These include derivatives having the C- or N-methyl group replaced by an ethyl group, homologues containing an additional 8-methyl or -ethyl group, and derivatives lacking the C- or the N-methyl group. Some related 2-ethylthio- and 2-dimethylamino-purines are also described, together with the 2-carbamoylmethylthiopurine (1; R = S·CH2·CO·NH2) and the oxidation product (1; R = SO2Me) from (1; R = SMe). From the S-methylation of 6-ethyl-9-methylpurine-2(3H)-thione (3; R1= Et, R2= Me), bis-(6-ethyl-9-methylpurin-2-yl) sulphide (4) was isolated as the major product.