Pyridine amidines

The simplest [3 + 3] reactions in the pyridine series involve reaction of o-chloropyridinecarboxylic acid derivatives with three-atom fragments such as urea, thiourea(s), amidines and guanidines, e.g. (240) (241). Examples are known mainly in... 

A different type of rearrangement occurs when suitable side chains are a to a pyridine-like nitrogen atom. In the monocyclic series this can be generalized by Scheme 43. For a given side chain the rate of rearrangement is l,2,4-oxadiazoles>isoxazoles> 1,2,5-oxadiazoles. Typical side chains include hydrazone, oxime and amidine. Some examples are shown in Table 9 (79AHC(25)147). Similar rearrangements for benzazoles are discussed in Section 4.02.3.2.4. 

The amino group of 8-amino-l,3,4,6,l 1,1 ln-hexahydro[l,4]oxazino[4,3-Z ] isoquinoline was reacted with 5-methyl-2-thiophenecarboximide hydroiodide in DMSO in the presence of pyridine at 50 °C for 4 h to give amidine 260 (X = 0) in 94% yield (97MIP4). 

Surprisingly, acetylation in hot pyridine yields the pyridinium salt 10. The amino group has amidine character and is resistant to diazotization, and condenses only with reactive aldehydes such as formaldehyde and trichloroacetaldehyde.41... 

Nickel, tris(l, 10-phenanthroline) racemization, 1,24. 466 solid state, 1, 467 structure, 1,64 Nickel complexes, 5,1-300 acetylacetone alcoholysis, 2, 380 pyridine complexes, 2, 386 solvolysis, 2,379 structure, 2,388 amidines... 

Titanium imido complexes supported by amidinate ligands form an interesting and well-investigated class of early transition metal amidinato complexes. Metathetical reactions between the readily accessible titanium imide precursors Ti( = NR)Cl2(py)3 with lithium amidinates according to Scheme 84 afforded either terminal or bridging imido complexes depending on the steiic bulk of the amidinate anion. In solution, the mononuclear bis(pyridine) adducts exist in temperature-dependent, dynamic equilibrium with their mono(pyiidine) homologs and free pyridine. 

The role of steric influences on the formation of various vanadium amidinate complexes in the oxidation states +2 and +3 has been studied in detail. The reaction of VCl2(TMEDA)2 and of VCl3(THF)3 with 2 equivalents of formamidinate salts afforded dimeric V2[HC(NCy)2l4 (cf. Section IV.E) with a very short V-V multiple bond and [ [HC(NCy)2 V(/i-Cl)l2 which is also dimeric (Scheme 107). The formation of V2[HC(NCy)2l4 was shown to proceed through the intermediate monomeric [HC(NCy)2l2V(TMEDA), which was isolated and fully characterized. The dinuclear structure was reversibly cleaved by treatment with pyridine forming the monomeric [HC(NCy)2l2V(py)2. ... 

Treatment of bis(pyridine) complexes of molybdenum and tungsten, M(f/ -allyl)Cl(CO)2(py)2 (M = Mo, W) with equimolar amounts of lithium amidinates Li[RC(NPh)2] (R = H, Me) afforded amidinato complexes of the type M(r -allyl)[RC(NPh)2](CO)2(py) (M = Mo, W). Reactions of the latter with acetonitrile, PEts, and P(OMe)3 have been investigated Free amidines react with M(r -allyl)Cl(CO)2(NCMe)2 according to Scheme 124 to give the corresponding bis(amidine) complexes. ... 

Closely related pyridine adducts were prepared as shown in Scheme 126 by treatment of the corresponding chloro precursor with lithium amidinates. 

Novel ruthenium-amidinate complexes of the type (j -CgHsRlRufamidina-te)X (R = Me, OMe, F X = Cl, Br, OTf) and [Ru(amidinate)(MeCN)4][PF6] have been synthesized by photochemical displacement of the benzene ligand in (j -CgHglRufamidinatelX by substituted arenes or MeCN. The acetonitrile ligands of [Ru(amidinate)(MeCN)4][PF6] are easily replaceable by other cr-donor ligands (L) such as pyridines, phosphines, and isocyanides to afford the corresponding derivatives [Ru(amidinate)(MeCN) (L)4 ][PF6] n — 1, 2). These reactions are summarized in Scheme 142. ... 

The coordination chemistry of ancillary amidinate ligands with a pyridine functionality has been described. Magnesium, aluminum, zirconium, and lanthanum complexes have been prepared in which the amidinate anions act as tridentate, six-electron-donor ligands Amidinate ligands containing quinolyl substituents were constructed in the coordination sphere of lanthanide... 

Oxalamidinate anions represent the most simple type of bis(amidinate) ligands in which two amidinate units are directly connected via a central C-C bond. Oxalamidinate complexes of d-transition metals have recently received increasing attention for their efficient catalytic activity in olefin polymerization reactions. Almost all the oxalamidinate ligands have been synthesized by deprotonation of the corresponding oxalic amidines [pathway (a) in Scheme 190]. More recently, it was found that carbodiimides, RN = C=NR, can be reductively coupled with metallic lithium into the oxalamidinate dianions [(RN)2C-C(NR)2] [route (c)J which are clearly useful for the preparation of dinuclear oxalamidinate complexes. The lithium complex obtained this way from N,N -di(p-tolyl)carbodiimide was crystallized from pyridine/pentane and... 

Cyclocondensation of 3-trifluoroacetyl substituted lactams with cyclic 1,3-bisnucleophiles gives pyrimido[l,2-a]benzimidazoles 21 and l,2,4-triazoloI4,3-a]pyridines 22. The use of amidines yields pyrrolopyrimidines <95JCS(P1)2907 94H(37)915>. 

Substituted pyrimidine N-oxides such as 891 are converted analogously into their corresponding 4-substituted 2-cyano pyrimidines 892 and 4-substituted 6-cya-no pyrimidines 893 [18]. Likewise 2,4-substituted pyrimidine N-oxides 894 afford the 2,4-substituted 6-cyano pyrimidines 895 whereas the 2,6-dimethylpyrimidine-N-oxide 896 gives the 2,6-dimethyl-4-cyanopyrimidine 897 [18, 19] (Scheme 7.6). The 4,5-disubstituted pyridine N-oxides 898 are converted into 2-cyano-4,5-disubsti-tuted pyrimidines 899 and 4,5-disubstituted-6-cyano pyrimidines 900 [19] (Scheme 7.6). Whereas with most of the 4,5-substituents in 898 the 6-cyano pyrimidines 900 are formed nearly exclusively, combination of a 4-methoxy substituent with a 5-methoxy, 5-phenyl, 5-methyl, or 5-halo substituent gives rise to the exclusive formation of the 2-cyanopyrimidines 899 [19] (Scheme 7.6). The chemistry of pyrimidine N-oxides has been reviewed [20]. In the pyrazine series, 3-aminopyrazine N-ox-ide 901 affords, with TCS 14, NaCN, and triethylamine in DMF, 3-amino-2-cyano-pyrazine 902 in 80% yield and 5% amidine 903 [21, 22] which is apparently formed by reaction of the amino group in 902 with DMF in the presence of TCS 14 [23] (Scheme 7.7) (cf. also Section 4.2.2). Other 3-substituted pyrazine N-oxides react with 18 under a variety of conditions, e.g. in the presence of ZnBr2 [22]. 

Almost accidentally, Bienayme and Bouzid discovered that heterocyclic amidines 9-76 as 2-amino-pyridines and 2-amino-pyrimidines can participate in an acid-catalyzed three-component reachon with aldehydes and isocyanides, providing 3-amino-imidazo[l,2-a]pyridines as well as the corresponding pyrimidines and related compounds 9-78 (Scheme 9.15) [55]. In this reachon, electron-rich or -poor (hetero)aromatic and even sterically hindered aliphatic aldehydes can be used with good results. A reasonable rahonale for the formation of 9-78 involves a non-con-certed [4+1] cycloaddition between the isocyanide and the intermediate iminium ion 9-77, followed by a [1,3] hydride shift. 

A,A-Dialkylformamide acetals (7) react with primary amines to give the corresponding amidines (8). Kinetics of the reaction of a range of such acetals with ring-substituted anilines—previously measured in neutral solvents such as methanol or benzene —have been extended to pyridine solution. In pyridine, the reactions are irreversible, with first-order kinetics in each reactant, and mechanistically different from those in non-basic solvents. Two mechanisms are proposed to explain Hammett plots for a range of anilines, in which the p value switches from negative to positive at a cr value of ca 0.5. The pyridine solvent substantially enhances the rate in the case of very weakly basic anilines. 

The involvement of an amidine group as C-N partner for interchange with the C(2)-N part of the pyridine ring has been observed during base treatment of the 3-formamidopyridinium salt 2-amino-3-formylpyridine is formed in a reasonable yield (Scheme IV.50) [79ZN(B)1019].The reaction follows the same pathway as described in Scheme IV.49. 

If the amino group of an AA is transformed into an amidine, cyclization can occur either with acetic anhydride in pyridine or with hydrazine to give... 

Tertiary benzylic nitriles are useful synthetic intermediates, and have been used for the preparation of amidines, lactones, primary amines, pyridines, aldehydes, carboxylic acids, and esters. The general synthetic pathway to this class of compounds relies on the displacement of an activated benzylic alcohol or benzylic halide with a cyanide source followed by double alkylation under basic conditions. For instance, 2-(2-methoxyphenyl)-2-methylpropionitrile has been prepared by methylation of (2-methoxyphenyl)acetonitrile using sodium amide and iodomethane. In the course of the preparation of a drug candidate, the submitters discovered that the nucleophilic aromatic substitution of aryl fluorides with the anion of a secondary nitrile is an effective method for the preparation of these compounds. The reaction was studied using isobutyronitrile and 2-fluoroanisole. The submitters first showed that KHMDS was the superior base for the process when carried out in either THF or toluene (Table I). For example, they found that the preparation of 2-(2-methoxyphenyl)-2-methylpropionitrile could be accomplished h... 

Setzt man als Amidin-Komponente Amino-hetarene (z. B. 2-Amino-pyridine, 2- bzw. 4-Amino-pyrimidine) ein, so erhalt man Imidazole, bei denen liber die Positionen 1 und 2 des Imidazol-Rings ein heterocyclischer Ring anelliert ist96 98 ... 

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