Formation and Destruction of Diazine Ring under Conditions of the Vilsmeier–Haack Formylation of 4-Dialkylaminonaphthalic Acid Derivatives Leonid D. Patsenker, * Inna G. Yermolenko, Yevgeniya Ye. Artyukhova, Vyacheslav N. Baumer and Boris M. Krasovitskii Institute for Single Crystals, National Academy of Sciences of Ukraine, 60, Lenin Avenue, Kharkov 61001, Ukraine Received 14 April 2000; revised 29 June 2000; accepted 13 July 2000 Abstract —The quaternized 1,3-diazine ring formation qualified as a particular case of the t-amino effect has been found under conditions of the Vilsmeier–Haack formylation of 4-dialkylaminonaphthalic acid derivatives. The diazinium ring is hydrolyzed in alkaline media with dealkylation, and 3-dimethylamino-4-alkylamino derivatives are formed.  2000 Elsevier Science Ltd. All rights reserved. Introduction Naphthalic acid derivatives are of considerable interest because many effective organic dyes and luminophores have been found among these compounds. 1 In the course of our systematic studies on the structure modification of such compounds, the behavior of some 4-dialkylamino- naphthalic acid derivatives under Vilsmeier–Haack reaction conditions is studied in this paper. Using semi-empirical quantum chemical simulations an electrophilic substitution in the 4-dimethylaminonaphthalic acid derivatives has been found to occur ortho to the dimethylamino group. 2 The Vilsmeier reaction is a suitable method for formylating active aromatic and heteroaromatic substrates. However, when the reaction is directed adjacent to tert-amino groups it can lead to cyclization of the intermediate iminium salt instead of formylation. Such cyclizations—the t-amino effect processes—were previously reviewed and classified with viewpoint of the nature of the reacting XvY bond and of the size of ring formed. 3 Results and Discussion We have found that some 4-dimethylaminonaphthalic acid derivatives, namely, the anhydride (1), N-methyl- (2) and N-arylimides (3), when being heated with POCl 3 in DMF at 100–130°C, give with good yield the water-soluble quater- nary salts 4 – 6 instead of expected carboxaldehydes (Scheme 1). These compounds contain a 1,3-diazinium ring annelated to the 3,4-positions of the naphthalic nucleus. Structures of compounds 4 – 6 were determined by 1 H NMR data. Besides this, the 6a structure was confirmed using X-ray diffraction analysis (Fig. 1). The independent part of the unit cell consists of two organic cations, two chloride ions and one water molecule. The expected carboxalde- hydes were not found among reaction products. This reaction seems to be similar as described previously for 4-dimethylaminotoluene. 4 Attempts to formylate it using POCl 3 in DMF or N-formylmorpholine gave the quinazo- linium salts (Scheme 2). The Vilsmeier–Haack formylation is known to proceed via some intermediates. 5,6 So, the reaction under consideration could be associated with cyclization in the Vilsmeier adduct A (Scheme 3). Mechanistically, it can run as one- step (Pathway a) or two-step (Pathway b) process. The PM3 7 quantum chemical simulations for the 1!4 reaction show enthalpy of activation (DH # ) 33 and 5 kcal/mol for the first and second stages of the two-step transformation A!B!4 correspondingly, while the 110 kcal/mol is calculated for the one-step mechanism. At the same time, Tetrahedron 56 (2000) 7319–7323 Pergamon TETRAHEDRON 0040–4020/00/$ - see front matter  2000 Elsevier Science Ltd. All rights reserved. PII: S0040-4020(00)00642-6 Scheme 1. Keywords: diazine ring; Vilsmeier–Haack formylation; 4-dialkylamino- naphthalic acid derivatives. * Corresponding author. Tel.: +380-572-307972; fax: +380-572-32073; e-mail: patsenker@isc.kharkov.com