Cyclocondensations of 1,2-Diamines

In the series of heterocyclizations of unsaturated carbonyl compounds, cyclocondensations based on ortho-diamines (or more specifically 1,2-diamines) are of particular significance. These reactions are characterized by the formation of different heterocycles with various (sometimes unexpected) structures. 

In the present chapter, an attempt is made to systemize the literature data and to analyze the rules of the reactions of 1,2-diamines, both the aromatic and the heteroaromatic nature, with chalcones for the synthesis of specific heterocycles. 

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A different approach to quinoxalines and heterocycle-fused pyrazines has been described by the Lindsley group, based on the cyclocondensation of 1,2-diketones and aryl/heteroaryl 1,2-diamines (Scheme 6.260) [450]. Optimized reaction conditions involved heating an equimolar mixture of the diketone and diamine components for 5 min at 160 °C in a 9 1 methanol/acetic acid solvent mixture, which furnished the substituted quinoxalines in excellent yields. This approach could also be applied equally successfully to the synthesis of heteroaryl pyrazines, such as pyr-ido[2,3-b]pyrazines and thieno[3,4-b]pyrazines. The same group has employed 1,2-diketone building blocks for the preparation of other heterocyclic structures (see Schemes 6.198, 6.268, and 6.269). 

Known from the literature are the heterocycle formation reactions from the interaction of 1,2-diamines with synthetic precursors of unsaturated ketones, i.e., the ones which contain an activated methyl or methylene group (Scheme 4.17). Since such cyclocondensations are obviously related to... 

In the cyclocondensation, in the second diamine group of 1,2-diamine both the ortho and ipso heterocycle atoms may react. Such a nontrivial result was obtained while studying the interaction of chalcones 157 and cyclic unsaturated ketones 161 with 5,6-diamino- 1,3-dimethyluracil 55 [61, 62]. This refuted the data [57] on the oxazepine 158 structure of the products of this reaction the formation of the spiro systems 159 and 162 was unambiguously proven... 

Cyclic amidines are prepared by the condensation of 1,2-diamines and p-ketoester derivatives [18]. Reaction of At-monomethyl-1,2-diamine and formylacetate acetal in the presence of an acid catalyst such as hydrochloric acid (HCl) or p-TsOH initially forms amidines by cyclocondensation. Elimination of ethanol to ethoxyvinyl amidine, followed by incorporation of a different 1,2-diamine, furnishes 1,3-dimethyl- and 1-butylimidazo-lidines (Scheme 3.7). This reaction is applied to the preparation of several kinds of diamines as a key step [19]. 

Cyclocondensation of a secondary diamine, (di-t-butylamino)methylborane, with an organotin dibromide, Me2Sn(CH2Br)Br, in the presence of butyllithium gives l,3-di-(-butyl-2,4,4-trimethyl-1,3,2,4-diazastannaborolidine (378) in 60% yield <87JOM(326)307>. 

The majority of reactions required to form these types of heterocycles involve the condensation of a 1,2-diamine and a 1,2-dicarbonyl compound, as shown in Equation (46) <2000H(52)423>. Other examples include the reaction of enaminones with carboxamides (Equations 47 and 48) <199681012, 2000T8489> and the cyclocondensation of a-ketoesters (Equation 49) <2001FA933>. Nicolaou and Li have prepared 99 and 100 by reaction of the diol 101 with a-bromoisobutyraldehyde (Equation 50) <2001AGE4264>. 

A hydroformylation-cyclocondensation of iV-alkenylpropane-1,3-diamines, such as 159 (prepared by reductive amination of the appropriate unsaturated aldehyde with either propane-1,2-diamine or 2-aminoethanol and subsequent borohydride reduction), in the presence of PPh3 and BIPHENPHOS as ligand provided different reaction products depending on the H2/CO ratio <1999AJC1131>. The bicyclic system 160 was accompanied by 10% branched 162 when H2/CO was 1 1 (Scheme 66). Reaction with H2/CO in a 1 5 ratio provided solely the bicyclic system, while only a mixture of monoalcohols 161 and 162 was isolated when the reaction was performed in the absence of PPh3. 

A novel one-pot approach for the synthesis of 2,4-disubstituted 3//-benzo[h] [1, 5]diazepines 115 has been disclosed by Muller and co-workers [163]. The compounds were obtained in good yields by the reaction of an acyl chloride, a terminal alkyne and a benzene-1,2-diamine via a consecutive one-pot, three-component Sonogashira coupling/Michael addition/cyclocondensation sequence, under micro-wave irradiation (Scheme 89). 

Cyclocondensation of aromatic and heteroaromatic 1,2-diamines with a.,/ -unsaturated carbonyl compounds 03MI10. 

Metal complexes of Schiff-base macrocycle can be prepared by cyclocondensation of pyridine-2,6-di-carboxaldehyde with benzene-1.2-diamine in the presence of Sr Pb -", or The metal-free mac-... 

Polyethylene glycol (PEG) has drawn considerable attention as a green reaction medium for organic synthesis [92]. Alkynes are successfiilly employed for the synthesis of Qxs using PdCyCuCl2 as the catalyst system in PEG-400 and water (8 2 Scheme 2.14) [93], The solvent system assists the oxidation of the alkyne to form the 1,2-dione as the intermediate species that undergo PEG-assisted cyclocondensation with the 1,2-diamine to form the Qx. 

Azide 367 is prepared from 4-r -butyl-2-nitroaniline in 76% yield by its diazotization followed by treatment with sodium azide. In a 1,3-dipolar cycloaddition with cyanoacetamide, azide 367 is converted to triazole 368 that without separation is directly subjected to Dimroth rearrangement to give derivative 369 in 46% yield. Reduction of the nitro group provides ortfc-phenylenediamine 371 in 91% yield <2000EJM715>. Cyclocondensation of diamine 371 with phosgene furnishes benzimidazol-2-one 370 in 39% yield, whereas its reaction with sodium nitrite in 18% HC1 leads to benzotriazole derivative 372, which is isolated in 66% yield (Scheme 59). Products 370 and 372 exhibit potassium channel activating ability <2001FA841>. 

There is not much literature on the chemical properties of fused dihydrodiazepine systems which are the products of cyclocondensation of chalcones with or /zo-diamines. In [105, 106] the properties of 2,4-diplhenyl and 2-methyl-2,4-diphenyl substituents of 2,3-dihydro-IH- 1,5-benzodiazepines, are adequately analyzed but not in a comprehensive manner. 

In our opinion, the reactions of chalcones 141 with some or /zo-diamines containing a hydrazine amino group (1,2-diaminobenzimidazole 142, 3,4-diaminotriazoles 143 and 1,2,4-triaminotriazoles 144) [122, 123, 124] are more interesting from both a practical and a theoretical viewpoint. The possibility to obtain the derivatives of azolopyrimidine 145—147 but not the triazepine systems in such reactions was demonstrated [124]. In this case the cyclocondensation is accompanied by the elimination of not only a molecule of water but also a molecule of ammonia. The proposed mechanism of the cyclocondensation [122] implies formation of a dihydroazolopyrimidine system with its subsequent heteroaromatization by amino-group elimination (Scheme 4.45). 

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