Amines formamidines

The formamidine is prepared by heating the primary amine in DMF-dimethylac-etal (81-100% yield). Deprotection is effected by heating in EtOH with ZnCl2. LiAlH4 (Et20, reflux), hydrazine (AcOH, MeOH), KOH (MeOH, reflux), dilute ammonia (high yield), and coned. HCl (reflux, 65-90% yield) are also known to cleave the formamidine group. 

Heating a primary amine with dibenzylformamide-dimethyl acetal in CH3CN gives the formamidine in 49-99% yield. It is cleaved by hydrogenolysis (Pd(OH)2, MeOH, H2O, H2, 52-99% yield). ... 

Reaetion of l-amino-2-eyanoquinolinium perehlorate 769 with triethyl orthoformate gave the formamidine derivative 770 whieh upon treatment with primary amines afforded the triazoloquinolinium perehlorate 771 (90H289) (Seheme 134). 

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

The first reductive kinetic resolution of racemic sulphoxides was reported by Balenovic and Bregant. They found that L-cysteine reacted with racemic sulphoxides to produce a mixture of L-cystine, sulphide and non-reduced optically active starting sulphoxide (equation 147). Mikojajczyk and Para reported that the reaction of optically active phosphonothioic acid 268 with racemic sulphoxides used in a 1 2 ratio gave the non-reduced optically active sulphoxides, however, with a low optical purity (equation 148). It is interesting to note that a clear relationship was found between the chirality of the reducing P-thioacid 268 and the recovered sulphoxide. Partial asymmetric reduction of racemic sulphoxides also occurs when a complex of LiAlH with chiral alcohols , as well as a mixture of formamidine sulphinic acid with chiral amines, are used as chiral reducing systems. ... 

Das zu Formel XX des allgemeinen Reaktionsschemas korrespon-dierende Zwischenprodukt XXVI reagiert mit weiterem Amin zum N.N -disubstituierten Formamidin (XXVII), dem Endprodukt in dieser Reaktionsfolge. 

Auch das einfachste Amin, Ammoniak, geht diese Reaktion ein (24), doch ist die Anwesenheit von HC1 zwecks Abfangens des Formamidin-hydrochlorids angebracht, so daB man in diesem Falle zweckmaBig NH3 in Form von Ammoniumchlorid einsetzt (27). 

Finally, Odom and co-workers reported a titanium-catalyzed three-component coupling between primary amines, alkynes, and isonitriles for the preparation of a, 3-unsaturatcd /3-iminoamines in good yields (Scheme 35).121 Beside the three-component coupling product, an. V,.V-disubstituted formamidine and an imine were also identified as minor... 

Dipolar cycloaddition reactions, of nitrones to olefins, 46, 97 of 3-phenylsydnone, 46, 98 Dispiro[5.1.5.1]tetradecane-7,14-dione, photolysis to cyclohexylidene-cyclohexane, 47, 34 preparation from cyclohexanecarbonyl chloride and triethylamine, 47, 34 Displacement of bromine from 1-bromo-2-fluoroheptane to give 2-fluoro-heptyl acetate, 46, 37 N,N -Disubstituted formamidines from triethyl orthoformate and primary amines, 46, 41 N,N-Disubstituted thioureas from secondary amines and silicon tetra-isothiocyanate, 45, 69 N,N-Disubstituted ureas from secondary amines and silicon tetraiso-cyanate, 45, 69... 

In addition, the pKa values of amidines substituted at the imino nitrogen atom correlate with the pKa values of the corresponding primary amines and, in turn, this correlation can be used to predict the pKa values of trisubstituted amidines. The pKa values of a series of trisubstituted formamidines (CyHs—N=CH—NR1 R2), with variable substituents at the amino nitrogen atom, correlate with the pKa values of corresponding secondary amines R1R2NH the correlations are in the following form ... 

Isoindole is an interesting precursor for successive alkylations at the a- and a -positions because both are benzylic. Oxazoline ° and formamidine auxiliaries have been used to accomplish the a,a -dialkylation to give a C2-symmetric amine. The C2-symmetric amine products are envisioned as possible tools for a variety of asymmetric processes. The diastereoselectivity of the second alkylation is enhanced by the presence of the stereocenter formed in the first alkylation (Scheme 61). ° Several other electrophiles were evaluated with the formamidine auxiliary. ... 

Despite the extensive use of microwave-enhanced reactions in order to effect syntheses, very little has been explored in the synthesis of thieno[3,2-i pyrimidines. One example of this newer technology being applied to heterocyclic systems involves the conversion of the formamidine 479 into 480 when treated with an amine under high-temperature microwave conditions (Equation 180) <20040L1523>. 

Cyclocondensation of ethyl 2-aminonicotinate in presence of HC(OEt)3 and various primary amines gave 22 3-substituted pyrido[2,3-,7]pyrimidin-4(377)-ones 371 <1995PHA719>. Fourteen 3,5,7-triarylpyrido[2,3-r7]pyrimi-dine-2,4(l/7,37/)-diones 372 have been prepared from the reaction of either 2-amino-3-cyano-4,6-diarylpyridines or the 3-carboxamido products of alcoholic KOH hydrolysis, with aryl isocyanates better yields were obtained from the amides <1995IJB740>. 4-Aminopyrido[2,3- pyrimidin-5(8//)-one 158 was synthesized by treatment of 2-amino-3-cyano-4-methoxypyridine with trimethylsilyl iodide to give the corresponding pyridin-4(177)-one, which was refluxed with formamidine acetate in ethoxyethanol to effect the cyclization <2000JME3704>. 

The synthesis of 6-substituted derivatives 626 was achieved via reaction of 2-substituted-5-aminopyridine-4-car-boxylic acids and formamidine acetate in boiling 2-methoxyethanol <1996J(P1)2221>. The pyrido[3,4- lpyrimidinone 628 was prepared by amination of the thioureido derivative 627 with diisopropylamine followed by cyclization in boiling DMF <2004FRP2846657>. Pyridine 627 was prepared from the corresponding 3-amino derivative with ethoxycarbonyl isothiocyanate in DMF. 

Nucleophilic attack at the fully conjugated 1,3,5-triazine usually results in ring cleavage. Thus, active methylene compounds react with 1,3,5-triazine in aminomethylenation reactions. A three-component reaction of cyclopentadiene with 1,3,5-triazine and a secondary amine leads to /V,7V-di substituted pentafulven-6-amines (304) and N2-(6-pentafulvenyl)formamidines (305)... 

Condensation of amine 277 with dimethylformamide dimethylacetal (DMF/DMA) gave A, A-dimethyl-./V -(5-methyl-l, 2,4-triazolo[l, 5-a]pyrim-idin-7-yl)formamidine (278), whose reaction with hydroxylamine gave the formamidoxime 279 (89EGP264438 90ZC320).The amine 280 and the hydrazine 282 can be transformed into the amidine 281 and amidrazone 283, respectively (90ZC320) (Scheme 54). 

By contrast, formamidine acetate is not hygroscopic and no particular care need be taken to protect it from atmospheric moisture. Furthermore, formamidine acetate can be used directly without prior treatment with base in syntheses requiring free formamidine.8,7-10 Finally, this preparation of formamidine is by far the simplest and most convenient yet reported it obviates the necessity of using either toxic (hydrogen cyanide) or cumbersome (Raney nickel) reagents, and the method can be adapted to the preparation of N,N -disubstituted formamidines by substitution of primary amines for ammonia.11... 

Formamidine-urea compounds (45) exchange imine fragments with primary amines (R4NH2) in non-protic solvents via the breakdown of the tetrahedral intermediate... 

After protection of the amine function under the form of a formamidine, silylation (80% yield) and deprotection via hydrazonolysis, propargyl amine is converted to the corresponding bis(silyl)propargylamine.128 130... 

Formamidines have been recognized as good activators for the a-deprotonation of amines at the a-position.141 Trapping the anions with trimethylchlorosilane led to the corresponding SMA.142... 

Derivatives to Amines (Deprotection of SMA) a. Hydrazinolysis of SMA Phthalimides and Formamidines... 

Formamidines are well known as protecting groups for primary amines. Hydrazinolysis has been used to recover the corresponding SMA.130... 

Trimethyl si lyl-Lo-acetonitrile has been shown to be highly versatile in the presence of cuprous chloride. Amines lead to formamidines through the insertion into their N-H bond whereas alcohols lead to desilylation products (see Section VLB).292... 

Formamidines such as 81 may be lithiated with s-BuLi or r-BuLi and give stabilised organolithiums 82 which react with a wide range of electrophiles. Cleavage is much easier than cleavages in the amide series acidic methanolysis gives a secondary amine 83 while hydride reduction gives a tertiary amine 84.57... 

Formycin A was initially isolated from rice mold <65JAN259> and identified <66JHC110, 66TL597) as 3-ribofuranosylpyrazolo[4,3-G ]pyrimidine-7-amine (54a). The reported synthesis utilizes the pyra-zole derivative (522) as starting material which is converted in situ on treatment with zinc dust in methanol in the presence of ammonium chloride into the amine (523) which is then reacted with formamidine to yield formycin A after deprotection (Scheme 53) <78CCC1431>. 

---