Unexpected Formation of a Tricycle in the Reaction of 1,3-Bis(Hydroxymethyl)Urea with Propane-1,3-Diamine*

Abstract

By contrast with the aminomethylation of thiourea by formaldehyde and primary amines to form 5-substituted 1,3,5-triazinane-2-thiones (see studies [1,2] and references therein) the aminomethylation of urea has not attracted so much work [3-10], the most recent being published in 1991. Because of the possibility of different condensations involving urea and formaldehyde [11,12] cyclic urea Mannich bases are better obtained not by a three-component condensation of urea, formaldehyde, and the corresponding primary amine [3-5, 7] but rather using 1,3-dimethylolurea (DMU) (1) [13], prepared from urea and formaldehyde, which then condenses with a suitable primary amine [7,8] or by condensing urea with the previously prepared dimethylol derivative of a primary amine with or without isolation of the indicated intermediate product [9]. The N-methylene derivative of a primary amine [10] may be used in place of the latter. Ethylenediamine and ethanolamine have been used [3][4][5] as bifunctional amines in a three-component condensation and ethanolamine and N,N-dimethylethylenediamine [7] in the condensation with DMU. In all four cases the expected 5-substituted 1,3,5-triazinan-2-one cyclic Mannich bases were obtained.

Reaction of thiourea with formaldehyde and simplest aliphatic diamines

“…Under the conditions reported in [5] for the formation of tricyclic docosane-4,14-dione [molar ratio N,N′-bis(hydroxymethyl)urea-propane-1,3-diamine 2 : 1, ethanol, reflux, 2 h], the reaction of 2 with propane-1,3-diamine afforded 94% of 5,5′-(propane-1,3-diyl)bis(1,3,5-triazinane-2-thione) (4) instead of expected tricyclic product 3. 1,3,5,7,11,13,15,17-Octaazatricyclo[15.3.1.1 7,11 ]docosane-4,14-dithione (3) was obtained in a poor yield (16%) when the condensation of 2 with propane-1,3-diamine was carried out with equimolar amounts of the reactants in isopropyl alcohol (Scheme 1).…”

“…a. Modified procedure [5]. A suspension of 5.45 g (40 mmol) of compound 2 in 22 mL of isopropyl alcohol was cooled to 3°C, 3.35 mL (2.96 g, 40 mmol) of propane-1,3-diamine was added under vigorous stirring, and the mixture was stirred for 10 min at 3°C, heated for 2 h at 68-75°C, and left overnight at room temperature.…”

“…Neither three-component condensations of thiourea (1) with formaldehyde and propane-1,3-diamine or butane-1,4-diamine nor two-component condensations of N,N′-bis(hydroxymethyl)thiourea (2) with ethane-1,2-, propane-1,3-, and butane-1,4-diamines were studied previously. By reaction of N,N′-bis(hydroxymethyl)urea with propane-1,3-diamine we previously obtained tricyclic 1,3,5,7,11,13,-15,17-octaazatricyclo[15.3.1.1 7,11 ]docosane-4,14-dione instead of expected 5-substituted 1,3,5-triazinan-2-one [5]. The present work was aimed at synthesizing a thioxo analog of the above tricyclic product starting from both thiourea (1) (i.e., via three-component condensation of thiourea with formaldehyde and propane-1,3-diamine) and from N,N′-bis(hydroxymethyl)thio-urea (2) (by condensation with propane-1,3-diamine).…”

“…Like the oxo analog [5], tricyclic dithione 3 may be regarded as macrocyclic Mannich base formed as a result of a multistep process with the difference that the substrate is thiourea rather than urea. The structure of 3 was determined on the basis of its NMR and mass spectra and X-ray diffraction data (see figure).…”

“…The 1 H NMR spectrum of 3 is similar to the spectrum of its oxo analog [5] and is represented by a characteristic set of multiplets. The signals were assigned, and the coupling constants 2 J and 3 J were determined, using 1 H-1 H COSY and 1 H-13 C{ 1 H} HMQC techniques.…”