The classic strategies for synthesizing alkoxy derivatives of nitrogen heterocycles are based on the nucleophilic substitution of good leaving groups. Among these are also nonoxidative methods occurring via a tele-mechanism. Hence heteroarenes with di-or trichloromethyl substituents react with alkoxide anions to give products of substitution of hydrogen in the ring by an alkoxy group [1][2][3][4].In the case of electron-deficient aza aromatic substrates a better alternative can be a direct oxidative nucleophilic substitution of hydrogen (ONSH [5]) by an alkoxy group since it does not need the preliminary introduction of good nucleofuges into the molecule. However, in the literature there are only individual examples of the successful alkoxylation of heterocycles via the ONSH process [6,7].In studying the reactivity of 1,3,7-triazapyrenes [8] relative to nucleophiles we unexpectedly found that they very readily undergo a double alkoxylation under unusual conditions. Reaction of 1,3,7-triazapyrene (1a) and its 2-methyl-substituted 1b with excess KOH and K 3 Fe(CN) 6 in aqueous methanol solution occurs at room temperature to give a high yield of the previously unknown 6,8-dimethoxy derivatives of this heterocycle (2a and 2b respectively). A similar reaction with 1a and ethyl or propyl alcohols gave the 6,8-diethoxy-(2c) and 6,8-dipropoxy-1,3,7-triazapyrene (2d). N N N R N N N R OR 1 1a,b R 1 OH, H 2 O KOH, K 3 Fe(CN) 6 2a-d R 1 O 2 a R = H, R 1 = Me (98%), b R = R 1 = Me (89%), c R = H, R 1 = Et (91%), d R = H, R 1 = Pr (69%)
The ability of the oxidative arylamination process to derivatize electron‐deficient 1,3,7‐triazapyrenes has been investigated. These triazapyrenes react with a wide range of sodium aryl(hetaryl) amides to give access to the corresponding 6‐aryl(hetaryl)amino‐1,3,7‐triazapyrenes in moderate to good yields. The reaction of 6,8‐dialkoxy‐1,3,7‐triazapyrene with sodium arylamides gives rise to 6,8‐bis(arylamino)‐1,3,7‐triazapyrenes or 6‐methoxy‐8‐arylamino‐1,3,7‐triazapyrenes, depending on the reaction conditions.
In previous work [1], we found that 1,3,7-triazapyrene undergoes double S N H alkoxylation by primary alcohols extremely readily in the ROH-H 2 O-KOH-K 3 Fe(CN) 6 system to give previously unreported 6,8-dialkoxy-1,3,7-triazapyrenes 1 at room temperature. These products may be considered as imino ethers, in which the C=N bond is located in a heteroaromatic ring. As in the case of esters of carboxylic acids, esters of imino acids undergo transesterification [2]. In the present work, we studied the feasibility of a similar reaction for dialkoxytriazapyrenes 1, which would expand the methods of synthesis of ethers of this heterocycle.We found that 6,8-dimethoxy-1,3,7-triazapyrene (1a) is readily converted at room temperature into diethoxy (1b, 77% yield) and dipropoxy derivatives (1c, 66% yield) by the action of excess sodium ethylate or sodium propylate in the corresponding absolute alcohol. However, the reconversion of 1b into 1a in the MeONa-MeOH system under the same conditions proceeds but is not complete even after 48 h. This finding is attributed to the insufficient solubility of substrate 1b in absolute methanol. Using acetonitrile as a cosolvent permits carrying out this reaction in only 4 h. As subsequently found, the use of absolute solvents is not necessary. The transalkoxylation of 6,8-dialkoxy-1,3,7-triazapyrenes proceeds readily at room temperature in the R 1 OH-MeCN-NaOH system (Table 1). N N N OR RO N N N OR 1 R 1 O R 1 OH, MeCN NaOH 1a,b,d 1a-dThus, 6,8-diethoxy-1,3,7-triazapyrene (1b) was obtained from dimethoxy derivative 1a in 85% yield. The reverse reaction proceeds to give 1a in 95% yield. 6,8-Dibutoxy-1,3,7-triazapyrene (1d) could not be obtained by the direct alkoxylation of 1,3,7-triazapyrene but was synthesized for the first time by the action of 1-butanol on 6,8-dimethoxy-1,3,7-triazapyrene (1a).
H -S N H alkoxylation.Classical strategies for the synthesis of ethers of nitrogen-containing heterocycles are based on the substitution of good leaving groups. Reactions proceeding by a tele-mechanism are among non-oxidative methods for obtaining such results. For example, heteroarenes with di-and trichloromethyl substituents react with alkoxide anions to give products of ring hydrogen substitution by an alkoxy group [1][2][3][4].In the case of electron-deficient aza-aromatic substrates, an excellent alternative may be direct oxidative nucleophilic substitution of hydrogen (ONSH [5]) by an alkoxy group, since it does not require a preliminary introduction of a good nucleofuge into the molecule. Yet we have found only two literature examples of successful heterocycle alkoxylation according to the ONSH process. Thus, the reaction of 1,3-dimethyllumazine with N-bromosuccinamide in the corresponding primary alcohol led to 6-alkoxy-and 6,7-dialkoxy derivatives of 1,3-dimethyllumazine [6]. Methoxylation of 2-nitro-5,10,15,20-tetraphenylporphyrin copper complex with sodium methoxide in DMF is reported in paper [7].Against this background, our previous observations of the easy ONSH alkoxylation [8,9], amination [10], and alkylamination [11] of 1,3,7-triazapyrenes is of great interest. Thus, the oxidative alkoxylation of 1,3,7-triazapyrene (1a) and its 2-methyl derivative 1b occurs at room temperature in the corresponding aqueous alcoholic solutions with an excess of KOH and K 3 Fe(CN) 6 [8], whereas compounds 1a and 1b remain unchanged in the conditions mentioned above [6]. With primary alcohols, the process results in the formation of previously unknown 6,8-dialkoxy derivatives of this heterocycle, 2a-d.The objective of the present work was a further investigation of this reaction, and also the possibility of hydrolytic cleavage of the ethers obtained.Allyl alcohol and ethylene glycol react with 1,3,7-triazapyrene (1a) under conditions used for the synthesis of compounds 2a-d, which allowed us to obtain also the 6,8-diallyloxy-(2e) and 6,8-bis(2-hydroxyethoxy)-1,3,7-triazapyrene (2f), respectively.
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