Carboxamides amidine

New rearrangements of 2-imino-2//-l-benzopyran-3-carboxamides, on their treatment with anthranilic acid, have been revealed. 4-Quinazolinones (72) have been prepared by rearrangement of 4-imino-4//-3,l-benzoxazines (71) via amidine carboxamides, while dihydrothiazines such as (73) which are disubstituted at C(7) have been observed to undergo a cyclization-ring contraction reaction with substituted acrylic acids to yield pyrroles (74). This interesting transformation has been accounted for by the route outlined in Scheme 23. 

Fmoc deprotection and sequential coupling of anthranilic acid and Fmoc-Gly yielded linear tripeptide 8, which could be cyclized to give immobilized oxazine 9. Treatment of 9 with piperidine cleaved the Fmoc group and promoted rearrangement of the oxazine into amidine carboxamide 10. 

From A(-substituted carboxamides, the 3-unsubstituted derivatives were formed, with loss of the corresponding amine. This reaction is to be expected from the mechanism of the ring closure amidine formation and subsequent nucleophilic attack of the amidine nitrogen on the carbonyl group. 

Heteropolyacids Hi4[NaPsW29MoOno] and H3PMO12O4 have been shown to be efficient catalysts for consecutive condensation of aldehydes with 5-aminopyrazole -carboxamide and cyclization into pyrazolo[3,4-t4pyrimidines <2007MI1467>. The reaction of ethyl 5-acylaminopyrazoles with hexachloroethane and triphenylphosphine in the presence of a base has been recently reported to afford an imidoyl chloride that reacted in situ with ethylamine yielding an amidine in 71% yield that cyclized readily in DMF in the presence of potassium carbonate to yield pyrazolopyrimidines in 65% yield <2007TL3983>. 

N1 -Carboxamide-N-Guanyi Triazene [Triazendi-carbon saureamid-amidin (Ger)] H2N.CO.N N.NH.C( NH).NH2+H2 Of C2H8N602 mw 132.16 N 63.60% OB to C02 +24.21% yel ndles (from hot w) mp, decomps explosively at 95°, puffs off at 139° on rapid heating. V sol in alkalies si sol in w. Prepn is by gently warming N-aminoim inome thy 1- N-carb onic acid ethyl ester-triazene with ammonia. The compd forms expl salts such as the Hydrochloride, C2H6N60+HC1 mw 167.09 N 50.31% ... 

The 4-aminopyrazole-5-carboxamide (381) cyclizes to give compound (383) on heating with chloroformamidine hydrochloride in DMSO it is most likely that intermediate amidine (382) is first formed (Scheme 35) <78NJC357>. 

A few 6- and 8-cyanopurines have been prepared and undergo characteristic nitrile addition reactions rather readily. Thus, alkaline hydrolysis produces carboxamides, then carboxylic acids, alcoholysis leads to imidates, ammonolysis to amidines, hydrazinolysis to amidhydrazines, hydroxylamine to amidoximes, and hydrogen sulfide to thioamides. Acid hydrolysis tends to give the decarboxylated acid derivative. Reduction either by sodium-ethanol or, preferably, by catalytic hydrogenation affords aminoalkylpurines and addition of Grignard reagents produces, in the first place, acylpurines. As with aldehydes, most of the compounds examined have been relatively non-polar derivatives. Table 28 lists some reactions and relevant literature. 

Amidines. Secondary amides (carboxamides) (1) when refluxed in HMPT give N.N-dimethylamidines (2) in fair yield. 

From Isatoic Anhydrides and Guanidine, Amidines, or Carboxamides... 

Imidazoles can also be made by heating 4-tosyloxazolines in saturated methanolic ammonia or monoalkylamines. These reactions proceed through intermolecular condensation of a-aminoketones and amidines and intramolecular cyclization of a-ainidinoketones, respectively [49] (see Section 4.2). When A -unsubstituted 4-oxazolin-2-ones are added to isocyanates, the 2-oxo-4-oxazoline-3-carboxamide products cleave under the influence of strong acids and heat. Subsequent ring closure gives 4-imidazolin-... 

Aminotriazole-5-carboxamide, trichloroacetamidine, and acetic acid, refluxed in ethanol, gave 4-(a-amino-/5,/5,/5-trichloroethylidinaminotriazole-5-carboxamide (35) (24 hr, 82%). Several N-alkylated 4-aminotriazoles behaved similarly. With other amidines, the reaction did not stop at this stage but produced an 8-azapurine [79JCS(P1)922]. 

This section will conclude with examples of the use of malonamideamidine [H2NC0CH2C(=NH)NH2] (which may be regarded as cyanoacetamide plus the elements of ammonia) in Scheme 1. Thus this amidine and phenyl azide, refluxed is sodium ethoxide, yielded 4-amino-3-phenyltriazole-5-carboxamide (1 hr, 33%) benzyl azide reacted similarly (38%) (57YZ455). The following example is both unusual and of preparative value. Malon-... 

Applications in organic synthesis of the iminoacylation reaction of oximes have recently been found at kinetically labile Zn11- or Con-oxime systems. The former catalyzes the hydrolysis of nitriles to carboxamides (23)37 and the Co11 system catalyzes the conversion of nitriles into amidines (24) (also involving C N bond formation upon reaction with ammonia, formed from competitive hydrolysis of the nitrile).110... 

Amidine and amine groups may be joined together to form this triazepinone ring by heating the compound with methanolic sulphuric add for 3h. The reactant is obtained by stirring isatoic anhydride (review of reactions [3008]) with an amidrazone (formally, a hydrazone of a carboxamide). 

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. ... 

The reactions of nitriles to give amidines, amides and ketone derivatives were only briefly mentioned in CHEC-I <84CHEC-I(3B)1>. The nitriles are reactive and, for example, 3-amino-4-pyridazinecarbonitriles are readily hydrolyzed in good yields to primary carboxamides with aqueous ammonia <88JHCl 19>. The enzymatic hydrolysis of pyridazine nitriles using Rhodococcus species has been investigated <92JHC93>. 

The CR NR group can be introduced into ammonia, amines, hydroxy compounds, carboxamides, and sulfonamides to form amidines, imido-esters, etc., via imidosulfonates, obtained by the Beckmann rearrangement of oxime sulfonates.—B Benzophenone oxime benzene sulfonate and aniline warmed in benzene, and, after the exothermic reaction has ceased, further refluxed for 15-30 min. —>- N,N -diphenylbenzamidine. Y 92.5%. (F. e. s. P. Oxley and W. F. Short, Soc. 1948,1514.)... 

The first step in the ring closure of carboxamide 107 (R=NH2) with imidates is the formation of an amidine intermediate, with subsequent nucleophilic attack of the imino group of the amidine on the carbonyl group this takes places with loss of the carboxamide iV-substituent [117]. This observation formed the basis of a simple synthesis of CHINOIN 143 enantiomers. From carboxamides 39 and 40 with ethyl m-chlorobenzimidate, 109 and 110 were obtained in high enantiomeric purity. The absolute configurations were determined by hydrolysis of 109 and 110 to the corresponding amino acid, which was identified by HPLC [79]. 

C-H bonds, 119 C-N bonds, 414, 417-418 sarcosines, 419 N-H bonds aliphatic, 373 amidines, 375 aromatic, 374 carboxamides, 375 O-containing, 374 S-containing, 372, 374 N-N bonds, 399 O-H bonds... 

Amidines were first condensed with o-aminoamides in 1965 when Baker and Kozma fused benzamide, 4-aminopyrazole-5-carboxamide, and sodium... 

Condensation of amidines with 4-amino-1,2,3-triazole-5-carboxamides (341) yields 2-substituted 8-azapurin-4-ones (342) and supplements a similar ring-closure of the amino-amides with amides (Scheme 131). ... 

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