Bicyclic amidines

DEHYDROHALOGENATION Amidines, bicyclic. N-Bromosuccinimide. I, S-Dia-zabicyclo[4.3.0 nonene-5. Diethylamine. Dimethyl sulfoxide. Hexamethylphosphor-ic triamide. Lithium bromide. Potassium r-butoxkle. Sodium amidc-Sodium r-but-oxide. Tetia-n-butylammonium bromide. Triethylamine. 

Aluminum bromide, 10,42,140 Aluminum chloride, 10-15,140,357 Aluminum cyclohexoxide, 15 Aluminum hydride, 357 AluminumOII) iodide, 106 Aluminum isopropoxide, 15-16 Amberlite-15, 266 Amberiite IR 120, 267 Amide acetals, 527-528 Amides, 424,456 Amidines, bicyclic, 16-18 Amine oxides, 270 p-Aminoacetophenone, 18 Amino adds, 252, 273, 368 Aminoalkenylation, 95 4-Aminobenzoic add, 45 2-Amino-3-cyano-5-chloromethylpyrazine 1-oxide, 459... 

Among other bicyclic amidine catalysts, 3,4,6,7,8,9-hexahydro-2//-pyrido[l,2-n]pyrimidine was also applied in the preparation of /3-alkoxy nitriles from Q ,/3-unsaturated nitriles and alcohols (99GEP 19803515). The azido group could be smoothly converted into a trifluoroacetylamido group by treatment with (Cp3CO)2 in the presence of Ph3P and 2,3-dihydro-2//-pyrido[l,2-n]pyrimidin-2-one under Ar in THE (99HCA2380). 

KOH is the most frequently used base, though stronger bases (OR , NH, etc.) or weaker ones (e.g., amines) are used where warranted.The bicyclic amidines l,5-diazabicyclo[3.4.0]non-5-ene (DBN) and are good reagents... 

Yields of Isomeric Bicyclic Pyrimidin-4-one (1100) and Pyrimidin-2-one (1101), Formed in the Reaction of EMME and Semicyclic Amidine... 

Cyclic amidines (213) react with chlorocarbonylsulfenyl chloride to give bicyclic 1,2,4-thia-diazoles. The product isolated from this reaction depends on the mode of addition. When (213) is added to chlorocarbonylsulfenyl chloride, 3-oxo derivatives (214) are isolated via the postulated intermediate (215). Addition of chlorocarbonylsulfenyl chloride to (213) leads to 5-oxo derivatives (216), via the proposed bis(intermediate) (217) (Scheme 47) <84CHEC-I(6)463). Cyclic amidines (213) have also been treated with 1-chloro-l-phenyliminomethanesulfenyl chloride (210) to afford 2>H-1,2,4-thiadiazoles (218). The other possible product from this reaction, the 2/7-isomer (219) has been shown to be unstable, rearranging to a benzothiazole. Heterocycles (213) which have been used in this transformation include 2-aminopyridine, 3-aminopyridazine, 2-aminobenzothiazole, 2-aminopyrimidine and 2-aminothiazole (Equation (33)) <86S1027>. 

Interest in the photochemistry of meso-ionic compounds is now developing, and an interesting result has been obtained by the photolysis of 5-amino-1,3-thiazolium salts (126, R = H). For example, irradiation of the salt 126, R = R = Ph, R = H, X = Cl, in aqueous solution yields the disulfide 130 (23%) and the keto amidine 131 (70%). It is proposed that this reaction involves a bicyclic intermediate (132). ... 

Ring contractions of 3H-azepines analogous to those outlined in Scheme 1 can give rise to either a 2-azabicyclo[3.2.0]hepta-2,6-diene (40) or the fused azetine (41). Odum and Schmall found exclusive formation of the 2-azabicycloheptadienes (40) for the 3H- azepines (2 R1 = H, R2 = OEt, NH2 or NMe2), and argued that the alternative pathway to the bicyclic azetines (41) would involve loss of amidine or imidate resonance in the product (69CC1299). 

Support-bound 1,2-diamines can be readily converted into imidazolidinones by treatment with carbonyl diimidazole [128,129]. The required diamines have been prepared on cross-linked polystyrene by reduction of peptides bound to MBHA resin with borane. Similarly, bicyclic imidazolines have been prepared from triamines and thiocarbonyl diimidazole (Entry 10, Table 14.3). Dehydration of polystyrene-bound monoacyl ethylene-1,2-diamines yields 4,5-dihydroimidazoles (cyclic amidines, Entry 5, Table 13.18). Several groups have reported the synthesis of 2-aminoimidazol-4-ones from resin-bound amino acid derivatives (e.g., Entry 6, Table 15.11). Most of these compounds are, however, unstable, and slowly decompose if dissolved in DMSO (Jesper Lau, private communication). 

In conjunction with other bicyclic amidines, the indolamine N-methyl transferase inhibitory activities of 3,4,6,7,8,9-hexahydro-2//-pyrido[ 1,2-a]-pyrimidines have been studied.246 The analgetic and antiinflammatory activities of 6-oxopy rido [1,2-a] pyrimidines have been tested in comparison with those of phenylbutazone.221,222... 

Alder, R. W. Sessions, R. B. Synthesis of medium-ring bicyclic diamines by the alkylation and cleavage of cyclic amidines. Tetrahedron Lett. 1982, 23, 1121-1124. 

Bicyclic amidines were obtained when the keteneimine 318 was heated in toluene solution to produce a formal [2+2] cycloaddition between the imine group and the C=C bond to give an approximately equal mixture of the diastereoisomeric azeto[l,2- ]imidazoles 153 and 319 in about 50% overall yield (Equation 36) (see Section 2.04.6.5) <2005T1531>. 

Chemoselective E2 eliminations can be carried out with sterically hindered, sufficiently strong bases. Their bulkiness causes them to react with an H atom at the periphery of the molecule rather than at a C atom deep within the molecule. These bases are therefore called nonnucleo-philic bases. The weaker nonnucleophilic bases include the bicyclic amidines DBN (diazabi-cyclononene) and DBU (diazabicycloundecene). These can be used to carry out chemoselective E2 eliminations even starting from primary and secondary alkyl halides and sulfonates (Figure 4.17). 

Similar reactions take place with other bicyclic amidines, e.g. 2,10-diaza-bicyclo[4.4.0]dec-l-ene, 2-methyl-10-diazabicyclo[4.4.0]dec-l-ene and 1,5-diazabicy-clo[4.3.0]non-5-ene. 

Bicyclic 1,2,4-thiadiazolones (293) are formed in moderate yields when cyclic amidines... 

In a series of publications (75JOC2600, 70JOC1965, 73JOC3087), Potts and coworkers have reported that cyclic amidines (290) readily condense with trichloromethylsulfenyl chloride (329) to yield the sulfenamides (330 Scheme 119). Treatment of the latter compounds with aromatic amines in the presence of triethylamine results in cyclization, possibly via an intermediate such as (331), to produce bicyclic products of type (332). Heterocycles (290) which have been used successfully in this reaction include 2-amino-l,3,4-thiadiazoles, 3-aminopyridazines, 2-aminopyrimidines, 2-aminopyrazines, 2-aminopyridines, 3-aminoisoxazoles and 5-amino-1,2,4-thiadiazoles. The sulfenamide derivative (330) of 2-aminopyridine also was found to react with sodium sulfide and with diethyl malonate to produce (333) and (334) respectively. Attempts to hydrolyze (332) to (295) under acidic conditions failed. 

Depending on their structural details, bicyclic amidines and amidinium salts hydrolyzed by K0H/H20 give ring-enlarged or ring-contracted lactams when hydrolyzed by K0H/H20 [8]. 

T. Kametani and K. Fukumoto, Heterocycles 7, 615-635 (1977). Tetrahydropyrimidines, condensed (bicyclic amidines) ... 

These compounds have been prepared in two ways from 3-amino-l,2,4-triazines. In the first case, the aminotriazine is converted into the amidine (359) with iV,iV-dimethylfor-mamide or -acetamide acetal. Reaction of the amidine with hydroxylamine produces the amidoxime (360) and cyclization with phosphorus oxychloride forms the desired bicyclic product (361) (77JOC1018). Also, the desired ring system can be synthesized by treating 3-amino-l,2,4-triazines with acetonitrile in the presence of aluminum chloride to afford the acetamidines (362) which, in one case (R = = Me), can be transformed into... 

Review Bicyclic amidines as reagents in organic synthesis." ... 

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