Form amidine Acetate

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

The 7-deaza EHNA analog 691 was obtained by condensation of 4,6-dichloropyrimidine-5-acetaldehyde with 674 The 1,3-dideaza EHNA analog was prepared from erythro-3-amino-2-nonanol (674) by condensation with l-chloro-2,3-dinitrobenzene, prepared in turn from l-amino-2,3-dinitrobenzene, to give 692. Reduction followed by cyclization with form-amidine acetate gave 693 (88JMC390). 

In an intramolecular reaction with, , A -diethylformamide or JV,JV-dimethylacetamide diethyl acetal, enaminones are known to react at the nitrogen to form amidines. The corresponding products from acetamide acetals can be converted to 2-aminoquinolines by condensation with DMF acetals or to 1,4-dihydroquinolines by cycloaddition with diethyl maleate (see Section II.A.5) (equation 26). 

Cyclic amidines are prepared by the condensation of 1,2-diamines and p-ketoester derivatives [18]. Reaction of At-monomethyl-1,2-diamine and formylacetate acetal in the presence of an acid catalyst such as hydrochloric acid (HCl) or p-TsOH initially forms amidines by cyclocondensation. Elimination of ethanol to ethoxyvinyl amidine, followed by incorporation of a different 1,2-diamine, furnishes 1,3-dimethyl- and 1-butylimidazo-lidines (Scheme 3.7). This reaction is applied to the preparation of several kinds of diamines as a key step [19]. 

A wide variety of /3-lactams are available by these routes because of the range of substituents possible in either the ketene or its equivalent substituted acetic acid derivative. Considerable diversity in imine structure is also possible. In addition to simple Schiff bases, imino esters and thioethers, amidines, cyclic imines and conjugated imines such as cinnamy-lidineaniline have found wide application in the synthesis of functionalized /3-lactams. A-Acylhydrazones can be used, but phenylhydrazones and O-alkyloximes do not give /3-lactams. These /3-lactam forming reactions give both cis and /raMS-azetidin-2-ones some control over stereochemistry can, however, be exercised by choice of reactants and conditions. 

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. 

The zinc complex formed with V,V -diphenylformamidinate is structurally analogous to the basic zinc acetate structure, as [Zn4(/i4-0)L6], and the basic beryllium acetate structure. It is prepared by hydrolysis of zinc bis(diphenylformamidinate).184 Mixed metal zinc lithium species were assembled from dimethyl zinc, t-butyl lithium, V.iV -diphenylbenzamidine and molecular oxygen. The amidinate compounds formed are dependent on the solvent and conditions. Zn2Li2 and... 

Amidines formed by condensation of 4-aminouracils with dimethylformamide dimethyl acetal are effective dienophiles, and form pyrimido[4,5-rflpyrimidines by [4-I-2] cycloaddition with isocyanates, isothiocyanates (Equation 83) <2005TL1433> and imines (Equation 84), A similar process has also been reported, using a nitrone as the dienophile (Equation 85) <2006BMCL3537>. 

Das 2-(2-Aryl-2-oxo-ethyl)-l-methyl-benzimidazol VI kann in zwei tautomeren Formen vorliegen. Es entsteht durch Kondensation von 2-(2-Methylamino)-anilin mit 3-Aryl-l,l-bis-[methylthio]-3-oxo-propen. Mit Elektronen-ziehenden Substituenten am Aryl-Rest liegt die Keten-N,N-Acetal-Form V vor, mit Elektronen-reichen Aryl-Resten die Amidin-Form... 

The quinoline-based tyrosine kinase inhibitor pelitinib (31-11) incorporates a Michael acceptor function in the side chain that can form a covalent bond with a nucleophile on the target enzyme. Such an interaction would result in the irreversible inhibition of the target kinase. Reaction of aniline (31-1) with DMF acetal leads to the addition of a carbon atom to aniline nitrogen in the form of an amidine (31-2). This intermediate is next reacted with nitric in acetic acid to form the nitrated... 

N, N -Diphenylacetamidine or Ethenyldiphenyl-amidine, CH3C(NH.CeHB) N.C6H6, mw 210.27, N 13 32% ndls (from ale), mp 132—33° insol, in w sol in eth St hot ale. It can be prepd by treating a cold mixt of 6 moles aniline St 3 moles acetic acid with 2 moles of PC13 and heating to l60°. This compd forms crystalline org St inorg salts (Ref 1). See also Ref 6 for prepn... 

The halonitro compounds and the methanol used were of purum or pract. quality from Fluka. The amidine derivatives (in the form of their salts) were purchased from Fluka or Aldrich (purum or pract.). The N,N-dialkyl-formamidine acetates were prepared by analogy to a published procedure (ref. 8) from cyanamide and used as isolated (containing ca. 10% ammonium acetate). 

Carboximidoyl chlorides may be reacted with oximes to give 30-65% yield of amidines, which may then be used to form imidazoles in good yields, by treatment with TsOH (equation 201)716. Highly substituted imidazoles may be prepared in a simple one-pot synthesis by treating vicinal tricarbonyl compounds with an aldehyde and ammonium acetate (equation 202)717. The reaction occurs in 66-90% yield and seems to be general in scope. 

Baumeister et al. studied the hydrogenation of various halonitrobenzenes using Raney Ni modified with amidine derivatives.115 Formamidine acetate (19b) has been found to be the most effective inhibitor for dehalogenation. It has been shown that the dehalogenation occurs as a consecutive reaction after the halogenated aniline has been formed. A typical example with use of this inhibitor is shown in eq. 9.51 for the hydrogenation of l-chloro-2,4-dinitrobenzene in comparison with dicyandiamide. It is noted that the reaction time could be shortened with 19b compared to that with 19a. 

Evidence that aminonitriles and 2-aminoindoles are the intermediates in this cycli-zation leading to indoles was obtained with a-substituted 2-nitrophenylacetonitriles. The final absorption of 1 mol of hydrogen was slow in the hydrogenation of 42, ammonia was not formed, and the aminonitrile 43 was the product, which cyclized to the oxindole 44 in the presence of acid. The hydrogenation of P-dimethylaminoethyl-sub-stituted nitronitrile 45 over 10% Pd-C in ethyl acetate at 80°C afforded ammonia and the indole 46. However, the hydrogenation of 45 over 8% Pd-C in acetic acid at 80°C did not result in the formation of an appreciable amount of ammonia, and a crystalline dihydrochloride corresponding to an amidine structure 47 could be prepared from the product (Scheme 9.17). 

Simultaneously, Woodward and co-workers (21) confirmed structure X for the alkaloid by chemical methods. They first recorded the caly-canine synthesis already mentioned. The intermediate tetraaminodi-aldehyde, first postulated by Robinson and Teuber (10), was also the basis for their structural speculations. The mercuric acetate oxidation product (dehydrocalycanthine) of Marion and Manske (13), formed by loss of two hydrogens, was smoothly converted by the action of alcoholic alkali into methylamine, and the resulting amide alcohol was written as XI. It was concluded that dehydrocalycanthine is an ene-imine, the relevant portion of the molecule being shown as XII. Other structures derivable from the tetraaminodialdehyde would more probably generate on amidine, and this would be impossible with X because of steric strain at a bridgehead double bond. 

Nitriles are also the usual products of oxidation of aliphatic amines RCH2NH2 by nickel peroxide and lead(IV) acetate. Aliphatic azo compounds can be prepared from these primary amines by first converting them into ulfamides (6), these then being oxidized with sodium hypochlorite or (better) r butyl hypochlorite (Scheme 9). A few aliphatic azo compounds can be formed in good yield by direct oxidation of r-alkylamines for example, AIBN was formed (86%) by oxidation of the amine Me2C(CN)NH2 with sodium hypochlorite. A special case of azoalkane foimation is the synthesis of chlorodiazirines (7) from amidines RC(= NH)NH2 by oxidation with sodium hypochlorite. ... 

These compounds have been prepared in two ways from 3-amino-l,2,4-triazines. In the first case, the aminotriazine is converted into the amidine (359) with iV,iV-dimethylfor-mamide or -acetamide acetal. Reaction of the amidine with hydroxylamine produces the amidoxime (360) and cyclization with phosphorus oxychloride forms the desired bicyclic product (361) (77JOC1018). Also, the desired ring system can be synthesized by treating 3-amino-l,2,4-triazines with acetonitrile in the presence of aluminum chloride to afford the acetamidines (362) which, in one case (R = = Me), can be transformed into... 

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). 

The reaction between a suitable imidatc and an a-aminoaldehyde or a-aminoacetal to form an amidine, which cyclizes to an imidazole, rests largely on the availability of the aminoaldehydes from a-amino acids, which are readily reduced using the Akabori method [2], Dimethyl or diethyl acetals frequently replace the aldehydes in these reactions 13,4]. Table 2.2.1 lists some 2,5-disub.stituted imidazoles prepared (ultimately) from amino acids. It is not possible to introduce a range of substituents at both the 4- and 5-positions by this method unless the amino acid is converted into a ketone rather than an aldehyde (see Section 2.1.1) (Scheme 2.2.2). 

The general approach of amidine cyclization ha.s been applied to the synthesis of a variety of 2-substitutcd imidazoles. Aminoacetaldehyde dimethyl and diethyl acetals are readily available commercially, and the N-subsiituted derivatives can be made with little difficulty, providing access to 1-substituted imidazoles on reaction with a suitable imidate. Thus, methyl -hydroxypropanimidate (2), prepared from 3-hydroxypropanenitrilc, and methanolic HCl, condenses with an aminoacetaldehyde acetal to give the amidine hydrochloride (3), which ring closes when heated in acidic medium to form the 1-substituted 2-hydroxyethylimidazolc (4) (Scheme 2.2.3) [6J. The reaction has been adapted to the preparation of 2-arylimidazoles [5, 7-11],... 

Thioamides can serve as surrogates for isothiocyanates in the Marckwald synthesis. For example, reaction of a-amino acetals 1278 with thioamides 1277 in the presence of HgClz affords amidine intermediates, which cyclize to form imidazoles under acidic conditions. This method has been applied to synthesize a variety of sugar imidazoles (Scheme 324) <2005HCA10, 2004HCA3035, 2004HCA719, 2000TA435>. 

A total synthesis of ( + )-mitomycins via isomitomycin A is described (87JA7881), and from a mitomycin rearrangement albomitomycin A and isomitomycin A were formed from mitomycin A (87JA7224). Amidine derivatives were prepared from mitomycin C and formamide acetals. These, when treated with amines, afforded the corresponding 7-N-substituted mitosanes (87JOC5601). 

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