Acylamidines

In comparison to N—S bond formation, O—N bond formation by essentially oxidative procedures has found few applications in the synthesis of five-membered heterocycles. The 1,2,4-oxadiazole system (278) was prepared by the action of sodium hypochlorite on A(-acylamidines (277) (76S268). The A -benzoylamidino compounds (279) were also converted into the 1,2,4-oxadiazoles (280) by the action of r-butyl hypochlorite followed by base. In both cyclizations A -chloro compounds are thought to be intermediates (76BCJ3607). 

The addition of acylazides leads to less stable triazolines, which lose nitrogen and rearrange to N-acylamidines (607). The triazolines obtained from sulfonylazides have been found to follow a similar reaction course as well as a path leading to the generation of diazoalkanes rather than nitrogen (596,599,608,609). 

A convenient synthesis of trisubstituted 1,3,5-triazines uses acylamidines 1 and amidines < 95JOC8428 >, whilst l,3,5-triazin-2(l/f)-ones 3 are obtained from N-acyl-lV -carbamoyl-S-methylisothioureas 2 <96H(43)839>. 

Succinimide is readily silylated by HMDS 2 to the N-silylated product 201, which seems, however, to be in equilibrium with the O-silylated derivative 202 a (cf the closely related reactive center in persilylated uridine 3) and reacts after 6-10 days at 24 °C with one equivalent of primary or secondary amines such as morpholine to give the crystalline colorless cyclic acylamidine 203 and HMDSO 7, even in the absence of any protective gas [33] (Scheme 4.12). The reaction is much faster on heating to 120 °C under argon. At these temperatures 201 and 202 a, and possibly also the acylamidine 203, are apparently partially O-silylated by HMDS 2 to the very sensitive 2,5-bis(trimethylsilyloxy)pyrrole 202b or to 2-tri-... 

In a related approach, the reaction of the acylamidine 201 (Scheme 29) with hydroxylamine results in loss of dimethylamine to give intermediate 202 which undergoes cyclization to give the 1,2,4-oxadiazole 203 <1999JME2218>. 

The intermediate acylamidine 244 functions as the three-atom component in reaction with hydroxylamine to give the [l,2,4-oxadiazol-5-yl]pyrazole 245, where the intermediate acylamidine 244 was obtained in good yield from reaction of the corresponding amide 243 with dimethylacetamide-dimethyl acetal (Scheme 37) <1999JME2218>. 

In 4,5-dihydro-1,2,4-oxadiazoles (82) the N—O bond breaks on irradiation to give A-acylamidines (83) (Equation (18)) <70JHC151, 88T4917>. Therefore, oxadiazolines (82) are sensitive to diffuse daylight. For R = t-butyl, elimination of RH occurs in preference to ring cleavage. 

Substituted acylamidines, such as (119), have been cyclized to oxadiazoles with hydroxylamine-0-sulfonic acid (Scheme 51) <9UMC1086>. Mechanistically related reactions include formations of oxadiazoles from oxazinium salts (120) (Scheme 52) <92KGS540>, and other oxadiazole-forming ring transformations <94H(38)ii3>, such as (121) (122) (Scheme 53) <89CB1107>. 

N—O bond formation by oxidative procedures has found less application. However, the 1,2,4-oxadiazole system (450) can be prepared by the action of sodium hypochlorite on N-acylamidines (449) (76S268). 

The synthesis of a fluorescent photochromic system 274a with a high fluorescence contrast ratio by covalently joining a highly fluorescent zinc bis(acylamidine) allowing effective energy transfer from the excited state of the dye to the photochromic component has been reported (08JPP(A) (200)74). 

Cyclizations of acylamidines 720 with amidines 721 or guanidines in aprotic solvents give -triazines 722 bearing three different substituents (Scheme 309) <1995JOC8428>. 

Electrocyclization is the key step in a route to 4//-imidazoles 1187 and imidazoles 1188. Thus, activation of AT-acylamidines 1183 with trifluoromethanesulfonic anhydride and subsequent condensation with amino compounds 1185 produces l-amino-2,4-diazapenta-l,3-dienes 1186. Deprotonation of 1186 by the use of strong organic bases yields the corresponding 4//-imidazoles 1187 or imidazoles 1188 after amine elimination through an anionic 1,5-electrocyclization reaction. For the cyclization to occur, the amino compound 1185 needs to possess electron-withdrawing substituents such as alkoxycarbonyl or fluorenyl groups (Scheme 290) <2004EJO2567>. 

By analogy with the 3-diketonates, the products (50) that result when (acylamino)dialkylboranes R2BNHCOR2 form complexes are considered as chelates of the ligand N-acylamidine.310 Spectroscopic data have been presented and reactions described in which both retention and degradation... 

Oxadiazoles can also be prepared from amides via acylamidines, ° or via the cycloaddition of nitrile oxides to nitriles, as illustrated. "" 3-Alkylamino-l,2,4-oxadiazoles result from the reaction of N-acyl-l-benzotriazolyl-l-carboximidamides with hydroxylamine. " ... 

Benzamidine reacts with the pyrazinooxazinone 14 at room temperature to give the acylamidine 15. Guanidines react similarly to give the acylguanidines 16. This approach to acylguanidines is particularly useful when the guanidine component is insufficiently nucleophilic to react directly with esters of pyrazine amino acids. The reaction has been extended to other substituted pyrazine amino acids. ... 

Triazines 5 with three different 2,4,6-substituents are conveniently prepared by cyclocondensation of acylamidines 4 with amidines [172]. Acylamidines result from amides and amide acetals. 

Gold s reagent"), the preparation of which is described in part A of the procedure, is a general 6-dimethylaminomethylenating agent which reacts successfully with amines (eq. 1) to produce amidines, with ketones (eq. 2) to produce enaminones, and with amides (eq, 3) to product acylamidines. ... 

Cyclizations of acylamidines 180 with amidines 181 or guanidines 182 in aprotic solvents gave r-triazines 183 bearing three different substituents (Scheme 26) <1995JOC8428>. 

Oxathiadiazine 2,2-dioxides 74 react readily with aqueous acid to produce (depending on substituents and conditions) A -acylamidines 104 or imides 105 (Scheme 8). Reaction of 74 (R = R = aryl) with alcohols in benzene in the presence of a small amount of water affords A -sulfamidines 106 (Scheme 8). Treatment of 74 with amines results in rupture of the C-O bond and formation of products such as 107 and 108 (Scheme 8) <1997CHE1028>. 

Oxadiazoles can be prepared by acylation of amidoximes or from amides via acylamidines. ... 

The above water-elimination reaction results in formations of amidines. Acylamidinium ions can also result from dehydration of the tetrahedral intermediates during the reactions of amino groups with acyllactams. Such groups could also be present within the polymer molecules. The water that is released in these reactions hydrolyzes the acyllactams, acylamidine salts, and lactam salts to yield carboxylic acids. ... 

Copper salt catalyzed G-insertion of isonitriles, CO, or diazo compounds into NH-bonds of amines gives good yields of form-amidines, formamides, or N-alkylated products respectively Recently, the analogous C-insertion of isonitriles into OH-bonds of alcohols has been reported . A variety of compounds, otherwise difficult to obtain, such as certain carbodiimides, acylamidines, or isonitriles, can be prepared by H2S-elimination with acylchloro-formamidines . 

Acylamidines Acylhydrazones a,a-Alkoxyaminonitriles N-Cyaniminoesters Diazo oxides Monoacyl-1,1-diamines... 

N2OC2 Acylamidines Acylamidinium chlorides Acylcyanamides Acylhydrazones N-Acylnitrilimines a,a-Alkoxyaminonitriles 1 -Alkoxycyanamides Aminomethoximes Azomethine imides Azine monoxides Carbamyl cyanides N -Cyaniminoesters Cyanoformamides... 

Dihydro-lf/-pyrrolo l,2-a benzimidazol-l-ones. A soln. of triphenylphosphine dibromide in methylene chloride added dropwise to a soln. of N-[2-aminophenyl]-2,5-pyrrolidinedione in the same solvent, 2 eqs. triethylamine added, and refluxed for 12 h - 2,3-dihydro-l//-pyrrolo[l,2-a]benzimidazol-l-one. Y 60%. F.e.s. H. Al-Khathlan, H. Zimmer, J. Heterocyc. Chem. 25, 1047-9 (1988) f. polycyclic acylamidines from azidophthalimides (with PPh3) cf. S. Eguchi, H. Takeuchi, J. Chem. Soc. Chem. Commun. 1989, 602-3. 

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