Amidines isomerization

There are differences in the high temperature behavior. While oxaziridines almost always isomerize to acid amides, a similar reaction of diaziridines, which should lead to amidines, has not been observed. Sensitivity towards bases, often encountered in oxaziridines, is observed only in some special substituted diaziridines. The tendency of some classes of oxaziridines to transfer the nitrogen function also lacks in the diaziridine field. On homolytic reactions of diaziridines there are only a few observations. 

In warm acetonitrile 7-piperidino-3-trityl-3i/-azepine (22) rearranges in high yield to the isomeric 3//-azepine 23.64 The corresponding 2-(pyrrolidin-l-yl) and 2-morpholino derivatives behave similarly. Presumably, the gain of amidine resonance energy in tautomer 23 is the driving force behind this rearrangement. 

Theoretically, valence isomerization of 3//-azepincs can give rise to 2-azabicyclo[3.2.0]hepta-2,6-dienes 20 and/or the isomeric fused azetines, 6-azabicycIo[3.2.0]hepta-2,6-dienes 21. Practically, however, 2-alkoxy- and 2-amino-3//-azepincs 19, on photolysis, yield the 2-azabicyclic systems 20 exclusively, since such structures are stabilized by imidate or amidine resonance.238... 

In the presence of N,N,N, N",N"-pentamethyldiethylenetriamine ( = PMDETA), monomeric lithium complexes of bulky formamidinate ligands can be isolated. The compounds (Scheme 12) comprise a Li(PMDETA) center coordinated by a bulky formamidinate in either the E-syn- or E-anti-isomeric form. Two of the structures display coordination of the pendant amidinate imine, and can therefore be considered the first examples of if. r -C = N,N metal amidinate coordination. ... 

The synthesis and characterization of the monomeric amidinato-indium(I) and thallium(I) complexes [Bu C(NAr)2]M[But(NAr(NHAr)] (M = In, Tl Ar = 2,6-Pr2CgH3) have been reported. Both compounds were isolated as pale yellow crystals in 72-74% yield. These complexes, in which the metal center is chelated by the amidinate ligand in an N, j -arene-fashion (Scheme 33), can be considered as isomers of four-membered Group 13 metal(I) carbene analogs. Theoretical studies have compared the relative energies of both isomeric forms of a model compound, In[HC(NPh)2]. ... 

The ammonioacetonitrile complex (206) reacts with NH3 to produce the amidine-bonded aminoacetamidine (207) complex, whereas in aqueous base it hydrolyzes to the amid o-A -bo ruled glycinamide complex (208).908 Acid-catalyzed linkage isomerization to first the O-bound form (209) precedes formation ultimately of the amino-bonded isomer (210) as the stable product upon deprotonation of the free amine above pH 6. 

In their synthesis of spirocyclopropanated oxazolines (see Section 2.1), the de Meijere group obtained initially unexpected cyclobutene-annelated pyrimidones 2-569 by reaction of the cyclopropylidene derivative 2-567 with the amidines 2-568. In this fourfold anionic transformation a Michael addition takes place to furnish 2-570, which is followed by an isomerization affording cyclobutenecarboxylates 2-572 and a final lactamization (Scheme 2.128) [294]. 

Muller and co-workers reported the three-component one-pot synthesis of various pyrimidines through the in situ generation of unsaturated carbonyl compounds. The palladium catalyzed coupling of aryl halides bearing electron withdrawing substituents 7 with propargyl alcohols 8 produced unsaturated carbonyl compounds 9 after isomerization, which condensed with amidines 10 to form triaryl pyrimidines 11 . 

The reaction of semicyclic amidines and EMME afforded a mixture of isomeric pyrimidin-4-ones (1100), (1101) (80BEP-883216, 80GEP3017625 82JHC909, 82M14). 

A detailed study of the reaction of semicyclic amidines and EMME revealed that the yields of isomeric pyrimidin-4-ones (1100) increased with increasing ring size (n) of the amidines when the ethanolic solution of the amidine was added dropwise to the ethanolic solution of EMME at - 10°C (see Table VIII) (82JHC909, 82MI4). 

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

These authors conclude that the problem of internal solvation is still an experimental and theoretical challenge GB measurements for this type of molecules of low volatility are not always in good agreement194. Molecular orbital calculations may help to solve the difficult experimental problems, but they have to take into account conformational isomerisms and the prototropic tautomerisms of the amidine and guanidine moieties. In light of the above discussion, the proton affinities deduced from the experimental GB values should be based on accurate estimations of the entropy of cyclization 86. 

In the reactions of cis- and rrans-2-aminomethyl-l-cyclohexanol or -1-cycloheptanol or cis- and trans-2-hydroxymethyl-l-cyclohexylamine or -1-cycloheptylamine with ethyl 4-chlorobenzimidate, the stereo- and regio-isomeric derivatives and homologs 164 and 165 were prepared (79T799). The amidine intermediate 166 of the benzimidate ring closure was also... 

A general procedure for the synthesis of 5-chloro-l,2,4-thiadiazoles (289) is the reaction of amidines with trichloromethylsulfenyl chloride (329) in the presence of an acid acceptor (Scheme 152) (also see Scheme 102). 3-Halo derivatives (387 X = Cl, Br, I Scheme 153) have been obtained in moderate yields from the corresponding amines (386) using the Sandmeyer-Gatterman reaction (Scheme 153) (60JCS3234) (see Section 4.25.3.3.4). 3-ChIoro-l,2,4-thiadiazolin-2-ones of types (298) and (299) can be prepared by treatment of chlorosulfenylcarbonyl chloride (291) with carbodiimides and cyanamides, respectively (Scheme 154) (70AG(E)54). The isomeric products (270) and (274) are produced by the chlorination of mixtures of isocyanates and isothiocyanates (Scheme 155) (see also Scheme 95). 

With )3-ketoesters, /3-ketoamides and )3-diketones, DAMN is converted into enamines, which can be cyclized purely by heating in an alcoholic solvent. The products are 2-substituted-4,5-dicyanoimidazoles (Scheme 2.1.5) [45], When DAMN reacts with formamidine, the initial condensation product (16)/(17) can form imidazoles either by loss of ammonia (when 4,5-dicyanoinnidazole is formed), or via an isomerization and subsequent cyclization which eliminates HCN to give 4-ainino-5-cyanoimidazole (18). With excess formamidine the latter product is converted into adenine. The intermediate amidines (16)/(17), as transient intermediates, react with aqueous ammonia to form (18), and with acetic acid to give (15) (R = R = H) [48, 50]. The transformation of (17) to (18) is a 1,5 bond formation (Scheme 2.1.6). 

Amidines with a more complicated substitution pattern have been prepared from amidines by alkylation—either at nitrogen or at nitrogen substituents. - Variations at these positions have been achieved by heteroarylation, acylation,vinylation or carboxylation with phosgene, thio-phosgene, isocyanide dichlorides or isothiocyanates. Some interesting amidines, e.g. (347)-(3S2) (Scheme 59), have been prepared in this manner. The amidine skeleton can also be varied by halogen-ation, - hydrolysis, isomerization or catalytic hydrogenation or other addition reactions if there are C=—C double bonds present as in (353 equation 173) for example. ... 

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