Amidines reaction with

Other amino substituted isoxazoles undergo ring-opening reactions on treatment with base. Thus the amidine derivative (249) gave the triazole (250) (64TL149), while the triazene (251) on reaction with ammonia gave the tetrazole (252) (64X461). 

During a study of azonitrones (70), Forrester and Thomson showed that reaction with toluene-p-sulfinic acid resulted in nitrogen evolution and formation of the hydroxamic acid (66) together with the pyrrolidone (71) and the amidine (72). These workers suggested the following reaction course. Although the yield of hydroxamic acid was high, the method is not likely to be of preparative value. 

Fusion of an additional heterocyclic ring onto that already present in the benzodiazepines has led to some medicinal agents with considerable activity. Treatment of an intermediate like 15 with phosphorus pentasulfide affords the corresponding thio-amide (37). Condensation of this intermediate with acetyl hydra-zide affords triazolam )37). The same agent can be prepared by reaction of the amidine, 38, ° with acetylhydrazide. ... 

Ammonium acetate, reaction with tn-ethyl orthoformate to give form-amidine acetate, 46, 39 Ammonium p chlorophenyldithiocarba mate, 46, 21... 

In a similar way, 1,3-dinitrogen systems such as diamines, amidines, guanidines, aminothiazoles, aminopyridines, ureas and thioureas react with alkynyl-carbene complexes generating the corresponding heterocycles. Of particular interest is the reaction with ureas, as the process can be applied to the easy synthesis of pyrimidine derivatives [88] (Scheme 41). 

We found that the optimal reaction protocol was to add a solution of a-bromo ketone in THF to the amidine in aqueous THF in the presence of potassium bicarbonate under vigorous reflux. Using this procedure, 2,4-disubstituted imidazoles were isolated in excellent yields with >95% purity without column chromatography. Aromatic and aliphatic a-halo ketones participate in this reaction with a variety of aromatic amidines, as indicated in Table 1. Particularly noteworthy is that reactions involving pyridylamidines or chloroacetone are substantially more robust using this process (entries 3 and 4). We have successfully used this protocol on a multi-kilogram scale. 

The synthesis of pyrido[2,3-d]pyrimidin-7(8H)-ones has also been achieved by a microwave-assisted MCR [87-89] that is based on the Victory reaction of 6-oxotetrahydropyridine-3-carbonitrile 57, obtained by reaction of an Q ,/3-unsaturated ester 56 and malonitrile 47 (Z = CN). The one-pot cyclo condensation of 56, amidines 58 and methylene active nitriles 47, either malonitrile or ethyl cyanoacetate, at 100 °C for benzamidine or 140 °C for reactions with guanidine, in methanol in the presence of a catalytic amount of sodium methoxide gave 4-oxo-60 or 4-aminopyridopyrimidines 59, respectively, in only 10 min in a single-mode microwave reactor [87,88]... 

As representative examples for the reactivity of the Cp Ti(amidinate) complexes some reactions with CS2 and COS are shown in Scheme 88. Other reagents that have been investigated in this study include carbodiimides, isocyanates, CO2, PhNO as well as aldehydes, ketones, and imines. ... 

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. ... 

Treatment of the bis(amidine) derivatives with a strong base such as Bu Li leads to conversion to the corresponding amidinato(amidine) complexes which on further reaction with triethylphosphine loose the coordinated free amidine as illustrated in Scheme 125. ... 

Thus unsubstituted (R=H) and substituted (R = alkyl) non-stabilized diyiides 1 react with phenylisocyanate and dicyclohexylcarbodiimide (R NCX), leading to the formation of new monoylide type intermediates. These last ones react in situ with carbonyl compounds through a Wittig type reaction leading respectively to a,)8-unsaturated amides 2 and amidines 3, with a high E stereoselectivity, the double bond being di- or tri-substituted [48,49]. By a similar reactional pathway, diyiides also react with carbonic acid derivatives, with the synthesis as final products of -a,/l-unsaturated esters 4 and acids 5 [50]. 

The behavior of Hg(CN)2 toward the dinuclear gold(I) amidinate complexes requires comment. In the case of the dinuclear gold(I) ylide, oxidation of the Au(I) to Au(II) resulted in the formation of a reduced mercury(O) product. Figure 1.19(a) [36]. In the mercury(II) cyanide reaction with the dinuclear gold(I) dithiophosphinate. Figure 1.19(b), the stability of the gold(I)-carbon bond compared... 

Gold(I) ylides are oxidized in 0.1 M [Bu4N]BF4/THFat low potentials of +0.11 and + 0.23 V vs. Ag/AgCl (quasi-reversible). The dinuclear amidinate oxidizes under the same conditions at + 1.24 V vs. Ag/AgCl (reversible). These large differences in chemical character of the dinuclear gold(I) complexes appear to explain the widely different behavior of these compounds and especially toward the reaction with mercury cyanide. 

A number of amidines have anthelmintic activity. Bunamidine (25), indicated for treatment of human pinworm infestations, is prepared from a-naphthylhexyl-ether (23) by Friedel-Crafts type reaction with cyanogen bromide and aluminum chloride to give nitrile (24). This, then, is reacted with the magnesium bromide salt of di-n-propylamine leading to the naph-thamidine structure (25). -... 

Aminoimidazolium salts (78) have been synthesized by the reaction of jV,AT-disubstituted amidines (79) with a haloacetonitrile. The formation of the salts (78) proceeds via the intermediates (80) (71BCJ826, 71JOC3368). These salts (78) can be acetylated with acetic anhydride, and the halide ion (X ) replaced by perchlorate or picrate anions (71BCJ826). 

Amidines and cyclic amidines are also converted into 1,2,4-thiadiazoles by reaction with isothiocyanates, imino-sulfenyl chlorides, di- and trichloromethyl sulfenyl chlorides, and carbon disulfide in the presence of sulfur. Ureas, thioureas, guanidines, carbodiimides, and cyanimides react with chlorocarbonylsulfenyl chloride to produce 1,2,4-thiadiazol-5-one derivatives in another example of a type B synthesis <1996CHEC-II(4)307>. 

The most common method for the preparation of the fully aromatized pyrimidine skeleton is the condensation of an amidine with an a,P-unsaturated carbonyl compound. For example, Palanki and co-workers reported that the reaction of amidines 1 with a,P-unsaturated carbonyl compounds 2 produced pyrimidines 3 <00JMC3995>. 

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