Amidine and nitrile

Triazoles have also been obtained when the carbon atom adjacent to the activated methylene group carries a nitrogen function (i.e., amides, nitriles, amidines, and imines - ). In many of these cases it is impossible to decide, without N-labeling experiments, whether the third nitrogen of the triazole ring is derived from the toluene-p-sulfonyl azide or from the activated methylene compound. With amides, amidines, and nitriles, the first possibility seems more reasonable, but with imines, the third nitrogen is that of the imino group (Scheme... 

Imidoyl amidines 1 can be synthesized starting from amidines and nitriles. Subsequent cycliza-tion with carboxylic acid anhydrides provides the corresponding 1,3,5-triazines 2. 

Continued interest (Vol. 1, p. 259) has been shown in the preparation of sy/M-triazines bearing fluorinated substituents. A review of perfluoroalkylene-triazine elastomers has been published two separate approaches (Scheme 59), the acylation-cyclodehydration of imidoylamidines, formed from amidines and nitriles, and the free-radical coupling of preformed triazine derivatives, have been used successfully to produce polymers of good linearity. 

Carboxylic acid tbioamides from amidines and nitriles Perfluorothioamides s. 13, 604 CSNH2... 

The other main reaction in this class is the Dieckmann-type cyclization of the intermediates (163) from 4(6)-halo-5-ethoxycarbonylpyrimidines with AC-substituted /3-alanine esters and nitriles, and related compounds, to give 5,6,7,8-tetrahydro-5-oxopyrido[2,3-[Pg.221]

It was found inadvisable to use more than four molecules of form-amide [ (47) when R = H] per molecule of anthranilic acid and the condensation produces best results when the mixture is heated at 120 -130°C for 2 hr followed by further heating at 170°-180 C for 2 hr. Other variants of this reaction involve the use of ammonium o-acylaminobenzoates, anthranilic acid in the presence of nitriles and acetic anhydride, o-acetamidonitrile with acetic anhydride or hydrogen peroxide, anthranilic esters and aliphatic or aromatic amides or amidines, isatoic anhydride with amides or amidines, and anthranilic esters with aryl iminochlorides in acetoned The mechanism proposed by Bogert and Gotthelf has had experimental supporR and is represented in Scheme 12. 

A -Silylmethyl-amidines and -thioamides (42) (X=NR or S) undergo alkylation at X with, for example methyl triflate, and then fluorodesilylation to give the azomethine ylides 43 (identical with 38 for the thioamides) (25,26). Cycloaddition followed by elimination of an amine or thiol, respectively, again leads to formal nitrile ylide adducts. These species again showed the opposite regioselectivity in reaction with aldehydes to that of true nitrile ylides. The thioamides were generally thought to be better for use in synthesis than the amidines and this route leads to better yields and less substituent dependence than the water-induced desilylation discussed above. 

Where R4 is a hydrogen or carbon atom, 10.15 is simply an amidine. However, urea 10.16, thiourea 10.17, or guanidine 10.18 and their derivatives may be used. These nucleophiles may be condensed with ester and nitrile functionalities as well as with aldehydes and ketones. Such condensations to afford pyridimidine derivatives are usually facilitated by acid or base catalysis, although certain combinations of reactive electrophilic and nucleophilic compounds require no catalyst at all. Some examples are shown below. 

Monoamines, primary diamines and secondary amines react with nitriles to give amidines, cyclic amidines and pyrimidines, respectively, in the presence of Yb(OTF)3 as a catalyst. Reaction of ammonia with acetonitrile is shown below. 

Nitriles also form dimers, e.g., [Ru2(NCMe)io]4+ other N-ligand species are amidinate and triazenido compounds such as Ru2(PhNCHNPh)2Cl235 and [Ru(l,3-diaryltriazenide)2(PPh3)2]0+,36... 

Dehydrohalogenation of amide chlorides affords a-chloroenamines, which undergo cycloaddition with IV-diphenylmethylaldimines to furnish azetidinium salts (303 equation 161). From these salts the diphe-nylmethyl group can be removed by hydrogenation, subsequent deprotonation yields 2-amino-1-aze-tines. The addition of primary or secondary amines to nitrilium salts gives rise to formation of amidinium salts and amidines respectively, e.g. (304 equation 162). In a similar reaction from copper(I) imidazolide, r-butyl bromide and nitriles amidines (305 equation 163) were prepared. ... 

Metal amides can be added to ordinary nitriles e.g. lithium, sodium or magnesium amides), thus forming amide imide salts, which on addition of water or alcohol afford amidines. Some recent results demonstrate the wide applicability of the method, e.g. from metal amides and trialkoxyacetonitriles, tri-alkoxyacetamidines (319 Scheme 52) were prepared and from lithium imides and nitriles A -alkylide-neamidines (320) could be synthesized. 

Many other functional groups are reduced by Sml. For example, sulfonyl halides are converted to disulfides. The reduction of nitro compounds by this reagent enables synthesis of 1,2-diamines based on a reaction sequence initiated by nitronate addition to aldimines, and in the presence of nitriles it furnishes amidines, and that of isothiocyanates in the presence of conjugated esters, the half thioamide derivatives of succinic esters. 

Amidines. Co-reduction of nitro compounds and nitriles by TiCl,j-Sm in THF leads to amidines. The intramolecular version requires lower temperatures as illustrated by the formation of 2-aminoquinolines. 

The six-coordinate tris(benzamidinates) [PhC(NSiMe3)2]3Ln also form 1 1 adducts with donor ligands such as THF, MeCN, or PhCN. In the case of ben-zonitrile, it was possible to isolate and structurally characterize two of these seven-coordinated nitrile-adducts. They are most readily isolated when the original preparation is directly carried out in the presence of one equivalent of benzonitrile (Scheme 15). The facile adduct formation with small donor molecules is yet another analogy between the tris(amidinates) and the tris(cyclopentadienyl) complexes, for which similar adducts with, for example, THF, nitriles or isonitriles are well established [6,7,17]. 

No doubt such a synthesis could be carried out. We might also explore the alternative disconnection of the six-membered ring. Opening up the amidine 30b at first looks unpromising but tautomerism between 36 and 37 reveals an amidine and an excellent disconnection to a nitrile 38 from which hydrazine can be removed to give the much simpler 39. Now we must use the same disconnection as 33 to give the same synthon 35 and the even simpler 40. 

Methods derived from this fundamental process involve the condensation of one-, two- and three-carbon units such as amidines, amino-nitriles and carboxamides, which represent intermediate stages of the ammonia/hydrogen cyanide reaction. Pyrimidines or imidazoles are usually intermediates. ... 

Synthesis of imino ethers, amidines and orto esters from nitriles (see 1st edition)... 

Symmetrical six-membered triazine rings can be synthesized from C-N units which are parts of nitrile groups, imidoyl halides, ureas, imido esters, amidines and guanidines. These reactants may be generated during the synthesis. 

Scheme 5. Preparation of silylated amidines from nitriles and subsequent reaction with (NSC1)3, SC12, SjNjCIj, etc.

Finally nitrile or isocyanide complexes may be attacked. Thus nitrile complexes with aromatic amines and alcohols give complexes of amidines and imidate esters respectively,298 e.g.,... 

Catalytic hydrogenation of oximes to amines requires conditions resembling those for catalytic hydrogenation of nitro compounds and nitriles.20d The catalyst should be as active as possible, e.g., Raney nickel101 (if necessary, platinized), platinum oxide,102 palladium-charcoal,103 palladium-barium sulfate,104 or rhodium-alumina.105 This rhodium catalyst also serves for reduction of an amidoxime to the amidine.106 Hydrogenation may be effected under pressure, but the temperature should be kept as low as possible to avoid formation of secondary amines. 

Thioimidic esters. These esters are convenient precursors of amidines and they are prepared from nitriles and PhSH in the presence of HBr. 

Amidines from amines and nitriles. CuCl activates ordinary nitriles towards attack by amines except those with low nucleophilicity (e.g., ArNH2). 

Amidines. Coreduction of nitroarenes and nitriles leads to amidines. For aliphatic y-nitronitriles an intramolecular coupling furnishes 2-amino-l-pyrrolines. 

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