Z. Naturforsch. 2020; 75(3)b: 317–326 Jan Szabo and Gerhard Maas* Derivatives of the triaminoguanidinium ion, 6. Aminal-forming reactions with aldehydes and ketones https://doi.org/10.1515/znb-2019-0216 [9]. Some years ago, we started to study the chemistry of Received December 5, 2019; accepted January 19, 2020 salts 3, which in particular were expected to undergo mul- tiple functionalization based on the nucleophilicity of the Abstract: Cyclic aminals (N,N-acetals) could be prepared benzyl-NH nitrogen atom. Thus, 3-Cl was found to undergo by the reaction of N,N′,N″-triaminoguanidinium sul- threefold N-carbamoylation with various arylisocyanates fate, N,N′,N″-tris(benzylamino)guanidinium chloride or and thiocarbamoylation (leading to thiourea derivatives) N,N′,N″-tris(benzylamino)guanidine with formaldehyde with arylisothiocyanates [10]. In a similar manner, triple or acetone. In all cases, 1,2,4,5-tetrazinane derivatives N-acylation with acid chlorides produced N,N′,N″-tris(N- were obtained, which were structurally confirmed by X-ray acyl-N-benzylamino)guanidines, which under the action crystal structure determinations. In two cases, 1:1 cocrys- of aqueous NaOH could be transformed into mesoionic tals of two different tetrazinane products were isolated. On 1,2,4-triazolium-3-aminides [11]. Reactions of salts 3 with the other hand, the reaction of N,N′,N″-tris(benzylamino) aldehydes or ketones have not been reported so far. guanidinium chloride with benzaldehyde yielded a The presence of three amino groups in the cations of 3-(2-benzylidenehydrazin-1-yl)-1H-1,2,4-triazole. salts 1–3 suggests, that cyclic aminals (N,N-acetals) could Keywords: 1,2,4,5-tetrazinane derivatives; aminal forma- result from their reactions with aldehydes or ketones. We tion; cyclic guanidinium salt; N,N′,N″-tris(benzylamino) report in this paper on so far unknown aminal forming guanidinium salt; triaminoguanidinium salt. reactions using formaldehyde, benzaldehyde and acetone as the carbonyl component. 1 Introduction 2 Results and discussion N,N′,N″-Triaminoguanidinium salts 1 (Fig. 1) are readily accessible, simple building blocks for organic synthesis, 2.1 Reaction of the triaminoguanidinium ion which due to their C3-symmetric topology and functional group presence offer diverse opportunities for the prepa- with acetone ration of other ionic or neutral guanidine derivatives and In an earlier paper, we have reported the synthesis of of nitrogen heterocycles [1, 2]. By reaction with aldehydes N,N′,N″-tris(propan-2-iminyl)guanidine 4 from 1 (X=Cl) or ketones, the three NH groups in 1 allow the straight- 2 and acetone [6]. A threefold condensation reaction prob- forward conversion into tris(imines) (or (tris(hydrazones)) ably gave rise to guanidinium salt 2, which, however, was 2 [2–6], some of which were employed as ligands with not isolated as a pure product. Rather, the solid residue multiple coordination sites in transition metal complexes obtained after evaporation of the solvent was treated showing remarkable three-dimensional architectures [2, with aqueous NaOH to furnish the neutral guanidine 4 5, 7, 8]. (Scheme 1). We report now, that under modified conditions N,N′,N″-Tris(benzylidenamino)guanidinium salts 3 two novel species could be isolated, which are likely inter- are easily prepared by catalytic C=N hydrogenation of mediates in the conversion of triaminoguanidinium ion 1 tris(benzylidenimino)guanidinium salts 2 (R1 = Ph, R2 = H) into N,N′,N″-tris(propan-2-ylidenamino)guanidinium ion 2. To this end, an anion exchange 1-Cl → 1-SO4 was per- *Corresponding author: Gerhard Maas, Institute of Organic formed by passing an aqueous solution of the former over Chemistry I, Ulm University, Albert-Einstein-Allee 11, an ion-exchange resin loaded with sulfate ions. When the 89081 Ulm, Germany, Fax: +49 (0)731 5022803, E-mail: [email protected] aqueous solution of 1-SO4 was exposed to acetone vapor, a Jan Szabo: Institute of Organic Chemistry I, Ulm University, Albert- crystalline precipitate was formed which was identified as Einstein-Allee 11, 89081 Ulm, Germany the double salt (5a, 5b) SO4 · 2H2O (30% yield after 3 days) 318 Jan Szabo and Gerhard Maas: Derivatives of the triaminoguanidinium ion, 6 the tetrazinane ring with axial benzyl substituents and trans-positioned vicinal triazole rings (Fig. 3); for a tetrazi- nane with analogous conformation, see ref. [16]. In contrast to formaldehyde, the reaction of benz- aldehyde with 3-Cl required harsher conditions and only Fig. 1: N,N′,N″-Triaminoguanidinium salts 1 and derivatives thereof. the 3-(2-benzylidenehydrazin-1-yl)-1H-1,2,4-triazole 7 was Scheme 1: Reaction of the N,N′,N″-triaminoguanidinium ion 1 with acetone. aAcetone as solvent, 4 days, r.t.; see ref. [6]. by an X-ray crystal structure determination (Fig. 2). We assume that a network of hydrogen bonds between NH groups, sulfate ions and water molecules accounts for the low solubility in the water-acetone reaction medium. Evidently, the two 2,3,4,5-tetrahydro-1,2,4,5-tetrazin- 1-ium ions 5a and 5b result from a cyclic aminal (N,N- acetal) formation involving two branches of 1 and the Fig. 2: Solid-state structure of the co-crystal of 5a (lower part of picture) and 5b with one SO 2− anion and two H O molecules in carbonyl compound. This process is similar to the forma- 4 2 the asymmetric unit (Mercury). Hydrogen bonds are shown as tion of five- or six-membered cyclic aminals from second- blue-violet dashed bonds. N–HLO hydrogen bonds connect both = 2− ary 1,n-diamines (n 1, 2) and aldehydes [12–14] or ketones cations with sulfate anions (one of the two SO4 ions shown does [13, 14] in aqueous reaction media. These preparations not belong to the asymmetric unit), and O–HLO hydrogen bonds have been shown to be equilibrium reactions [13, 14]. between sulfate anions and water molecules are also present. For the sake of clarity, not all short intermolecular contacts are shown. Moreover, evidence for the reversibility of the aminal syn- Selected bond lengths in 5a (Å): C1–N1 1.322, C1–N3 1.323, C1–N5 thesis from imines and primary amines comes from trans- 1.348, N1–N2 1.426, N3–N4 1.425, N5–N6 1.417, C2–N2 1.480, imination reactions in organic solvents [15]. By analogy it C2–N4 1.479. Selected bond lengths in 5b (Å): C5–N7 1.322, C5–N9 was not unexpected that further exposure of isolated (5a, 1.336, C5–N11 1.342, N11–N12 1.390, N7–N8 1.417, C6–N8 1.479, C6–N10 1.477, N10–N9 1.428(3); all estimated standard deviations 5b)SO4 · 2H2O followed by deprotonation with aqueous ± NaOH furnished the neutral guanidine derivative 4, which are at 0.003 Å. was identified by its 1H and 13C NMR signals (see ref. [6]). 2.2 Reaction of the N,N′,N″-tris(benzylamino) guanidinium ion with aldehydes The reaction of N,N′,N″-tris(benzylamino)guanidinium salt 3-Cl with paraformaldehyde under acidic condi- tions furnished the symmetrically tetrasubstituted 1,2,4,5-tetrazinane 6 in moderate yield (Scheme 2). The molecular structure was confirmed by an XRD analysis, Scheme 2: Reaction of tris(benzylamino)guanidinium salt 3-Cl with which revealed a centrosymmetric chair conformation of aldehydes. Jan Szabo and Gerhard Maas: Derivatives of the triaminoguanidinium ion, 6 319 Fig. 3: Solid-state structure of 6 (Ortep). The molecule has a crystallographic inversion center. Torsion angle C11–N2–N1i–C2i 135.95°. finally isolated in modest yield (Scheme 2). An XRD struc- is isostructural to a COOH group, and analogous homo- ture determination (Fig. 4) revealed the identity of 7 and dimers are often found in solid-state structures of carbox- also showed, that in the crystal structure centrosymmet- ylic acids; furthermore, the same hydrogen bond pattern ric dimers are present, which are held together by two occurs in several 3-amino-1,2,4-triazolium carboxylate N–HLN hydrogen bridges. A hydrogen-bonded eight- complexes [18]. In the crystal structure of the parent 2 membered ring motif is thus created (graph set R(2 8) 3-amino-1H-1,2,4-triazole, on the other hand, all nitrogen [17]). The 3-amino-1H-1,2,4-triazole moiety H–Namino–C=N atoms are involved in a network of hydrogen bonds, but Fig. 4: Solid-state structure of 7 (Mercury). A centrosymmetric dimer is shown, which is maintained by two N–HLN hydrogen bonds [distances (Å): N2LN4 3.042(2), N4–H 0.89(2), N2LH(N4) 2.19(2); angle N2LH–N4 159.3(16)°]. 320 Jan Szabo and Gerhard Maas: Derivatives of the triaminoguanidinium ion, 6 trapped in 1,3-dipolar cycloaddition reactions [21, 22]. In the presence of benzaldehyde, 3-Cl does not appear to react in the same manner; instead, a spontaneous ben- zylamine → benzylimine dehydrogenation could generate hydrazone 7. 2.3 Reaction of N,N′,N″-tris(benzylamino) Scheme 3: Proposed mechanism of the reaction of 3-Cl with guanidine with acetone aldehydes. N,N′,N″-Tris(benzylamino)guanidine (10) is readily obtained by base-assisted deprotonation of guanidinium centrosymmetrical eight-membered cyclic dimers as in 7 salt 3-Cl with aqueous NaOH (Scheme 4). We noticed, are not present [19]. however, that the aqueous solution of 3-Cl instantanously A mechanistic proposal for the reaction of triami- developed a yellow color on contact with the base and noguanidinium salt 3-Cl with formaldehyde (generated turned orange on prolonged standing. Control experi- in situ from paraformaldehyde) or benzaldehyde is pre- ments showed this phenomenon to occur only in the pres- sented in Scheme 3.