4- 2- pyrimidin benzonitrile

An unusual final example of a synthesis from pyridines involves the 4-lithiotetra-chloropyridine (128), which with two moles of benzonitrile gave the trichlorodiphenyl-pyrido[3,4- f]pyrimidine (130) via the intermediate (129) (72JCS(P1)2190). The 2-lithio analogue gave the corresponding [3,2-c] derivative. 

Corsaro and co-workers studied the reaction of pyridazine, pyrimidine, and pyrazine with benzonitrile oxide and utilized H NMR spectral analysis to determine the exact structure of all the cyclized products obtained from these reactions <1996T6421>, the results of which are outlined in Table 1. The structure of the bis-adduct product 21 of reaction of pyridazine with benzonitrile oxide was determined from the chemical shifts of the 4- and 5-isoxazolinic protons at 3.76 and 4.78 ppm and coupled with the azomethine H at 6.85 ppm and with the 5-oxadiazolinic H at 5.07 ppm, respectively. They determined that the bis-adduct possessed /(-stereochemistry as a result of the large vicinal coupling constant (9.1 Hz). Similarly, the relative stereochemistry of the bis-adducts of the pyrimidine products 22-25 and pyrazine products 26, 27 was determined from the vicinal coupling constants. 

An interesting series of extended pyrimidine analogues was described by Davoll and Johnson Scheme 3.59) [164]. Reductive animation of an appropriately substituted benzonitrile (323a-c) with p-aminobenzoyl aspartic acid followed by saponification gave (324a-c). The m-substituted compound (326) was prepared analogously starting with (325). 

To give the reader some perspective of the large range of 15N chemical shifts, secondary aliphatic amines such as pyrrolidine have chemical shifts in the range of 38 ppm, aniline (54), primary amides ( 105), benzonitrile (256), pyridine (317), pyrrole (146), pyrazole N-1 (207), N-2 (399), imidazole (211), pyridazine (400), pyrimidine (295), and pyrazine (333).9... 

An unusual synthesis of a pyrrolo[2,3- ]pyrimidine without a functional group is based on the reaction of benzonitrile with A-methyl-2-pyrrolidone. These two compounds, when heated in the presence of sodium telluride, give low yields of 2,4-diphenyl-7-methylpyrrolo[2,3- ]pyrimidine <93JOC24l>. The yields could not be improved, thereby limiting the usefulness of the method. 

Table 2. Electronic origin (in nm) of the excitation spectra (as obtained from the LIF spectroscopy and REMPl-TOF-MS) of 4-dialkylamino derivatives of benzonitrile (I, II, IV) and pyrimidine (VHX), methyl 4-dimethylaminobenzoate (XI) and their clusters with various polar solvent molecules [the displacement in cm (- denotes the red shift and + the blue shift) of the 0,0 transitions of the clusters with respect to the monomer origin are included]... 

The yields of the pyrimidines 147 and the pyridines 151 are not high and vary greatly, depending on the structure of the starting materials. The latter can also determine the nature of the product. Thus, a mixture of 2,4-dimethyl-6-phenylpyrimidine, 2,4-dimethyl-4,6-diphenyl-4//-l,3-oxazine and 1-chloro-l-phenylethene was obtained by refluxing a 1 3 3 ratio of the acetophenone-benzonitrile-phosphorus oxychloride mixture, followed by treatment of the crude product with sodium carbonate solution .It has been shown that addition of an additional ketone molecule to the iminium intermediate is an alternative to the formation of the A -acylenamines and this route is catalyzed by aluminum chloride. Auricchio and coworkers believe also that the reaction of ketones with nitriles catalyzed with both protic and Lewis acids must be considered as a Ritter reaction (see, however, Section V.C). The cationic intermediate 152 thus formed can undergo either a proton shift giving enamide 153 or addition of another ketone molecule... 

Nitriles have also been used as cyclization partners. Thus, nicotinonitrile cyclizes with 2-amino-nicotinonitrile to give 2-(3-pyridyl)pyrido[2,3-r/]pyrimidin-4-amine (64).127 The electron-withdrawing effect of the pyridine group in nicotinonitrile, or of the trichloromethyl group in trichloroacetonitrile,128 appears to be essential for the reaction since benzonitrile does not react with 2-aminonicotinonitrile under the given conditions the dimer of 2-aminonicotinonitrile, 2-(2-amino-3-pyridyl)pyrido[2,3-r/]pyrimidin-4-amine,129 is obtained instead.127... 

Treatment of tetrachloro-2-pyridyllithium (1) with an excess of benzonitrile in refluxing hexane gives a 9% yield of 6,7,8-trichloro-2,4-diphenylpyrido[3,2-r/]pyrimidine (3). The reaction with one mole of benzonitrile at room temperature after aqueous workup affords 12% of 2-benzoylte-trachloropyridine, evidence for the intermediacy of the corresponding 2-ketimine anion 2.422... 

The reaction converting tetrachloro-2-pyridyllithium by treatment with benzonitrile into a pyrido[3,2-(/]pyrimidine, affords, by starting from tetrachloro-4-pyridyllithium (1), 5,6,8-trichloro-2,4-diphenylpyrido[3,4-d]pyrimidine (2) in low yield.394,422... 

Synthesis of 3-substituted 6-arylbenzo[r/][l,2,3]triazin-4(3/f)-ones using polymer bound triazenes has been reported <04JCO38>. Gas-phase thermolysis of thieno[3,2-e][l,2,4]triazines yielded benzonitrile, isothiazole, pyrimidine, [ 1 benzothieno[2,3-dJpyrimidine and thieno[3,2-rf thiazole derivatives. These products were separated by HPLC and column chromatography and characterized using GCMS, LCMS, H, C-NMR and 2D NMR spectroscopy... 

Nitriles can also be substituted for formamide. Benzonitrile and 2-aminobenzonitrile, autoclaved at 200°C, gave a moderate yield of 4-amino-2-phenylquinazoline (see 1). This reaction resembles, and is competitive with, the dimerization of aminonitriles discussed above it also proceeds by a similar mechanism. Other examples are the condensation of 3-cyanopyridine with 2-amino-3-cyanopyridine to give 2-(3-pyridyl)-4-aminopyrido[2,3-d]-pyrimidine (see 3) and of 5-cyano-l-methyl-4-aminoimidazole (see 18) with... 

Interesting constructs of molecules such as pyrrolo-pyridines, pyrrolo-quinolines, pyrrolo-pyrazines, pyrrolo-quinoxalines and pyrrolo-pyrimidines could be constructed by intramolecular Chichibain-type reaction. Davis and co-workers were the first to show the first of these examples, where p-methylazines react with nitriles to give the corresponding fused bicycle in the presence of excess base (2.5 equiv). For example, P-picoline reacts with benzonitrile in the presence of LDA to give the pyrrolo-pyridine adduct 61 in a 90% yield and traces of 62a. Under similar conditions and if... 

In addition to hydrogen halides, water is the most studied HBD in the gas phase. The structures of the complexes with water, dinitrogen, carbon monoxide, ozone, benzene, ethane, formaldehyde, formamide, 1,4-dioxane, ethylene oxide, tetrahydropyran, difluo-romethane, pyrazine, pyrimidine, pyridazine, benzonitrile, quinuclidine, ammonia, methy-lamine, trimethylamine and so on can be found in the Mogadoc database [29]. In the water-morpholine complex [30], water is hydrogen bonded to the nitrogen and not to the oxygen, as predicted by the higher HB basicity of amines than that of ethers. 

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