Formamidines formation from

The formation of the chiral formamidine 1658 from octahydroisoquinoline 1656 and the isocyanide 1657 derived from valinol tert-butyl ester gives an intermediate with high chirality-inducing potential, which, through further reaction steps, allows an asymmetric synthesis of (+)-morphinane with high enantiomeric purity (>98% ee in the decisive asymmetric reaction step) [1229]. The isocyanide 1657 is obtained in 85% yield by dehydration of the corresponding formamide with thionyl chloride. 

N,N -Disubstituted formamidines, N-substituted from triethyl ortho formate and pnmary amines, 46, 41... 

Kislyi et al. facilitated the formation of [l,2,3]triazolo[4,5-r lpyrimidin-7-ones from 5-amino-l,2,3-triazole-4-carbox-amides under Vilsmeier conditions (Scheme 47) or using triethyl orthoacetate and acetic anhydride (Scheme 48) <2003RCB1770>. These methods could be used to isolate the respective 5-formamidine 69 and 5-imidoate 70 reaction intermediates, if lower temperatures and shorter reaction times were employed. 

Unlike formamidine, acetamidine and benzamidine react with both aromatic and aliphatic a-hydroxyketones to give imidazoles exclusively. It has been suggested that aryl groups favour the enolic form (2) of the tautomeric mixture, resulting in the formation of oxazoles as major products. Aliphatic groups favour the keto form (1), from which imidazoles are derived. That amidines more complex than formamidine favour imidazole formation may be a consequence of steric hindrance to reaction of the enolic hydroxy groups with the amidine carbon in (2). The general reaction has been used to prepare such compounds as 4,5-dipropyl imidazole (25% yield from tris(formylamino)-methane and 5-hydroxyoctan-4-one), and a variety of 2-imidazolones and 2-aminoimidazoles [8]. The fact that oxazoles can be converted into imidazoles with some ease extends the applicability of this reaction. 

Phosphorus nitrile chloride forms adduct (10) with DMF in the ratio 1 4, which is useful for the preparation of formamidines and azavinylogous formamidinium salts. It is supposed that the dehydration of primary amides to nitriles with (PNChls as well as the formation of 2-alkylbenzothiazoles from 2-(methylthio)anilides and (PNChls in the presence of triethylamine proceed via similar adducts." ... 

Formamidines are accessible from 2-diaIkylamino-2-aIkoxyacetonitriles (360 Scheme 63) and primary amines. The action of HCN on the nitriles (360) gives rise to formation of A7-vinylamidines (361). ° Formamidines (362) are formed from bis(dialkylamino)acetonitriles and isocyanates in excellent yields. This reaction is interesting from the mechanistic point of view. 

An attempt to prepare 5-methyladenine (176) from the imidazole (175) and formamidine resulted in the formation of the imidazotriazine (177) (Scheme 84). ... 

Formamidine acetate was prepared in similar high yield by a similar procedure but with glacial acetic acid as solvent.804 A A-Disubstituted formamidine and acetamidine derivatives have been obtained analogously from orthoesters and alkylamines in the presence of glacial acetic acid805 or boron trifluoride etherate 806 In the reaction of orthoesters with secondary amines in the presence of toluenesulfonic acid the formation of ketene aminals (alkyl l -amino-vinyl ethers) was also observed.807... 

Formation of the purine system probably occurs by way of the aminoimidazolecarboxamide 24 according to method 2 24 results from the interaction of aminocyanoacetamide 22 and formamidine acetate (methanimidamidium acetate) 23 derived from NH3, ammonium acetate and HC(OR)3. 

Insertion into C—H bonds is also a reaction type common to nitrene chemistry. This is observed in the formation of the cyclopropylamine 615 from reaction with 1-ethoxy-l-trimethylsilyloxycyclopropane. Details have been reported of the use that can be made of the addition of the same nitrene to the chiral silyloxyalkene 616. This leads to an asymmetric synthesis of the amine 6YT. Insertion of a nitrene into C—H bonds is also reported for the photodecomposition of/7-trimethylsilylbenzoyl azide in hydrocarbons Reports have been made concerning the non-specificity of this particular nitrene. Apprently, some control can be exercised on its reactivity by using a micellar system. Under conditions of this type, using N, A-dimethyloctylammonium propionate as the micellar material, only the formamidine 618 is obtained ... 

The chloroformamidines are basic compounds, but their base strength has not been reported. However, it is indicated that the alkylchloroformami-dines are considerably more basic than the aryl derivatives because moderate heating causes elimination of hydrogen chloride from disubstituted aryl-chloroformamidine hydrochlorides ( ). N-Arenesulfonyl-N -alkylchloro-formamidines are almost neutral compounds because no hydrochloride formation was observed... 

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