Diamines cyclocondensation

A completely different kind of macro cycle, a calix-salen type macrocycle, was obtained in good yield by microwave irradiation of various dialdehydes and diamines [165]. This was the first example of a calix-type synthesis under microwave conditions and without the presence of a metal template. An example of a [3 -1- 3] cyclocondensed macrocycle 265, obtained from a bis aldehyde and a chiral diamine is reported in Scheme 97. 

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). 

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>. 

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>. 

Appropriately substituted hydroxy amides and ureas can be used instead of diamines. Thus, acid-catalyzed cyclocondensation of iV-carbamoyl prolinols 137 (R1 = H, (CH2)3) (Scheme 27) with aldehydes RCHO (R = Ph, 2-MeOC6H4, 2-naphthyl, etc.) stereoselectively afforded a series of pyrroldine-fused oxadiazepinones 46 (Scheme 5) <1990CPB2627, 1990H(30)287, 1996LA927>. Similar heterocyclization of 4-(2-hydroxyethylthio)-2-azetidinone with acetone dimethyl acetal was used in the synthesis of azetidinone-fused oxathiazepanes of type 33 (X = S) (Figure 4) <1980JA2039>. 

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. 

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... 

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). 

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... 

The formation of pyrazoline derivatives 175 (but not dihydrotetrazolotria-zepines 173, as assumed earlier [53]) is brought about by the condensation of chalcones with diaminotetrazole 172 [128,129]. The structure of the compounds 175 is convincingly verified using X-rays. The mechanism of their formation implies a Dimrothe rearrangement for either the initial diamine or for one of the cyclocondensation intermediates (Scheme 4.51). 

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. 

Therefore, the one-pot three-component approach to benzo[b][l,4]diazepines 51 by virtue of alkynones as key intermediates commences with the coupling of (hetero)aroyl chlorides 7 and terminal aUcynes 4, and concludes by subsequent addition-cyclocondensation of ort/io-phenylene diamines 50 under dielectric or conductive heating to furnish the desired seven-membered heterocycles (Scheme 30) [173], A related three-component synthesis according to our concept enabled the synthesis of benzo[b][l,4]diazepines 51 in water under conductive heating [174],... 

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). 

Methoxy-5-nitroquinoxalines, not easily obtainable by direet nitration, ean be prepared by cyclocondensation from 4-methoxy-3-nitrobenzene-l,2-diamine with a-dicarbonyl compounds. Several related heteroeyelie systems such as isoxazolo[4,5-h]pyraziiie... 

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