H. Antaki, The Reaction of α-Ethoxymethylenecarboxylic Esters with Some Cyclic Amidines,
J. Am. Chem. Soc. 1958, 80, 3066–3069.
DOI: 10.1021/ja01545a041
H. Antaki, Some Pyrido[1,2-a]pyrimidones,
J. Org. Chem. 1962, 27, 1371–1374.
DOI: 10.1021/jo01051a058
Last updated: 4 October 2026
H. B. F. Antaki's published ultraviolet investigation of pyrido[1,2-a]pyrimidin-4-ones developed from structural work already documented in his 1950 doctoral thesis. The thesis used ultraviolet spectral comparison as supporting evidence for structural identity; the 1958 Journal of the American Chemical Society paper, received 15 October 1957 (DOI: 10.1021/ja01545a041), extended the work systematically across the fused pyrido[1,2-a]pyrimidine class; and the 1962 Journal of Organic Chemistry paper (DOI: 10.1021/jo01051a058) tested and refined the chromophore interpretation by altering molecular structure and observing the corresponding spectral changes. The work combined synthesis, structural interpretation and ultraviolet absorption spectroscopy, while the published papers also document a parallel programme of antischistosomal investigation.
The first UV spectra in this record appear not in a published paper but in Antaki's 1950 doctoral thesis. Two hand-drawn curves (Fig. I, Fig. II) are compared directly and described as "nearly identical," used as confirming evidence that two differently obtained bases shared the same ring system.
![Doctoral thesis, 1950: Fig. I and Fig. II, hand-drawn UV absorption curves for the two pyrido[1,2-a]pyrimidinone-type bases compared as 'nearly identical'](/thesis-uv-figs-1-2.jpg)
In the thesis, the decisive constitutional evidence was chemical. An independent synthesis was described as providing "unequivocal proof" for 2-methyl-4-keto-1-aza-4-quinolizine. The ultraviolet comparison supplied additional structural evidence: Antaki wrote that the nearly identical spectra "indicates the presence of identical nuclei in the two compounds" and, together with their chemical behaviour, provided "further evidence for the correctness of the structures assigned."
The corresponding published structural correction appeared in 1951 in H. Antaki and V. Petrow, Extended pyrido[1,2-a]pyrimidine ring systems, J. Chem. Soc. 1951, 551–555 (DOI: 10.1039/JR9510000551). The published paper established the 4-oxo structure by independent synthesis; the thesis preserves the additional UV reasoning.
In 1952, Roger Adams and Irwin J. Pachter independently demonstrated that ultraviolet spectra could distinguish the 2-one and 4-one pyrido[1,2-a]pyrimidinone isomers in Ultraviolet Spectra and Structures of the Pyrido[1,2-a]pyrimidones, J. Am. Chem. Soc. 1952, 74, 5491–5497 (DOI: 10.1021/ja01141a079).
The link between the thesis and the later published record is documented by Antaki himself. In Some Pyrido[1,2-a]pyrimidones (1962; DOI: 10.1021/jo01051a058), he cites his 1950 thesis in connection with the observation that the spectrum displays two bands. The paper also records that spectra shown there had been determined in his laboratory in 1958 "in conjunction with work carried out on the ultraviolet spectra of pyrido[1,2-a]pyrimidones," documenting continuity of the programme.
In Antaki's 1958 paper (DOI: 10.1021/ja01545a041), ultraviolet spectroscopy was used at several levels: spectral similarity supported structural assignments of open-chain intermediates; comparison with independently constrained products was used to establish an unexpected mode of cyclisation; and the spectra of the fused products were then interpreted as a class.
"A constant feature in the spectra of this class of compounds is the presence of a band with intense absorption in the region 330–390 mμ."
In modern units, the quoted range is 330–390 nm.
For the long-wave absorption, Antaki related the fused compounds to the N-substituted pyridone-2-imine chromophore. The comparison drew on Leigh C. Anderson and Nelson V. Seeger, The Absorption Spectra of the Aminopyridines, J. Am. Chem. Soc. 1949, 71, 340–342 (DOI: 10.1021/ja01169a097). Antaki attributed the shift and intensification in the fused compounds to conjugative interaction with the β-amino-α,β-unsaturated ketone or nitrile system.
Antaki also placed this interpretation in the context of earlier work. Referring to H. R. Snyder and Michael M. Robison, Structure and Reactions of Malonyl-α-aminopyridine. I, J. Am. Chem. Soc. 1952, 74, 4910–4916 (DOI: 10.1021/ja01139a052), Antaki wrote:
"Such a view has previously been advanced solely on the basis of chemical and infrared spectral evidence."
Snyder and Robison had previously proposed the zwitterionic formulation on chemical and infrared grounds. Antaki explicitly acknowledged that work and supplied an independent ultraviolet line of evidence, concluding that the fully aromatic zwitterionic structures made a major contribution to the resonance state of the pyrido[1,2-a]pyrimidinone system.
"This may be considered as evidence for the major contribution of zwitterionic fully aromatic structures such as VIII to the resonance state of the molecule."
In Antaki's 1962 paper (DOI: 10.1021/jo01051a058), the shorter-wave band near 245 mμ was assigned to the –C=C–C=O chromophore of the pyrimidine moiety. The importance of the paper lies not only in assigning this second band, but in experimentally testing the chromophore rules established for the class.
Antaki altered the molecular structure and examined whether the ultraviolet spectrum changed in the predicted direction. Introduction of an unsaturated substituent shifted the shorter-wave absorption. A carboxamido derivative substantially increased the intensity of that band while leaving the longer-wave N-substituted pyridone-2-imine absorption chiefly unaffected. Dihydro-oxo derivatives supplied further comparative evidence. The spectra were therefore being used not simply as fingerprints, but to separate experimentally the contributions of different chromophores within the fused molecule.
The comparative method was extended to 7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one and 5-methyl-s-triazolo[2,3-a]pyrimidin-7-one in the same 1962 paper. This allowed the common –C=C–C=O absorption of the pyrimidine moiety to be distinguished from the second absorption associated with the chromophore contributed by the fused cyclic amidine.
The use of ultraviolet comparison continued beyond the 1958–1962 pyridopyrimidinone programme. In H. Antaki, Some Derivatives of Decahydro-1,8-dioxoacridine, J. Chem. Soc. 1965, 2263–2264, comparative ultraviolet absorption spectra were reported for the deca- and octahydro-9-p-nitrophenyl-1,8-dioxoacridines. This documents continued structural use of ultraviolet spectroscopy in Antaki's later fused-ring chemistry.
Antaki's earlier structural work had already demonstrated that chemical behaviour alone could leave competing constitutional possibilities unresolved. In the 1951 structural study (DOI: 10.1039/JR9510000551), oxidation by itself could not distinguish between the competing constitutional structures. The decisive solution was independent synthesis.
At a time before routine modern NMR structure elucidation, ultraviolet absorption supplied an additional physical means of testing structural assignments when conventional chemical behaviour could be ambiguous. In Antaki's work the progression can be followed directly: spectral identity as supporting structural evidence in the 1950 thesis; diagnostic and class-wide spectral behaviour in 1958; and chromophore assignment tested through controlled structural modification in 1962.
The spectroscopy was carried out alongside biological work at the Research Institute for Tropical Medicine. In the 1958 paper, certain pyrido[1,2-a]pyrimidine esters were reported to produce a "hepatic shift on oral administration to Gerbils experimentally infected with Schistosoma mansoni."
The 1962 paper explicitly continued this line, referring to "previous work on the schistosomicidal activity in the pyrido[1,2-a]pyrimidine series" when considering the synthesis of basic derivatives. The papers therefore document spectroscopy, synthesis and antischistosomal screening proceeding within the same research programme.
M. Shur and S. S. Israelstam, The Reaction of Aminoheterocycles with Reactive Esters. I. Aminopyridines, J. Org. Chem. 1968, 33, 3015–3020 (DOI: 10.1021/jo01272a002), described 4H-pyrido[1,2-a]pyrimidin-4-ones as showing a characteristic two-band ultraviolet spectrum. Their paper cites Antaki's 1958 work for the approximately 350 mμ N-substituted pyridone-2-imine assignment and his 1962 work for the approximately 245 mμ –C=C–C=O assignment.
In their 1983 specialist review, István Hermecz and Zoltán Mészáros, Chemistry of Pyrido[1,2-a]pyrimidines, Advances in Heterocyclic Chemistry 1983, 33, 241–330 (DOI: 10.1016/S0065-2725(08)60055-0), summarized Antaki's interpretation as follows:
"Antaki concluded that the absorption band for the 2-oxo-2H- and 4-oxo-4H-pyrido[1,2-a]pyrimidines in the range 300–400 nm can be ascribed to the 2-imino-1-substituted-1,2-dihydropyridine chromophore, and the band in the interval 250–270 nm to the C=C–C=O chromophore of the molecules."
This later specialist account identifies Antaki's contribution specifically as the assignment of characteristic absorption regions to structural chromophores. In this sense, the later literature preserves the chromophore rules established by Antaki: the longer-wave absorption associated with the N-substituted pyridone-2-imine chromophore and the shorter-wave absorption associated with the C=C–C=O chromophore of the pyrimidine portion of the molecule.
Ultraviolet absorption spectroscopy was already an established structural technique before Antaki's work, and earlier ultraviolet studies existed for aminopyridines and related pyrido[1,2-a]pyrimidinones. The contribution documented here is more specific.
Beginning with spectral comparison as supporting structural evidence in his 1950 doctoral thesis, Antaki developed a continuous programme in which ultraviolet absorption was used first to support structural identity, then to identify characteristic behaviour across a fused heterocyclic class, and finally to assign and experimentally distinguish the structural chromophores responsible for its principal absorption bands.
The sequence can therefore be stated precisely: 1950 — structural evidence; 1958 — systematic class-level absorption behaviour; 1962 — experimental separation and interpretation of the underlying chromophores. Later specialist literature retained these assignments and attributed them to Antaki.