Amination of benzoxazoles

Typical Procedure for Iodine-Catalyzed Amination of Benzoxazoles [102]. 234... 

Catalytic amounts of Co(OAc)2 or Mn(OAc)2 in combination with ferf-butyl hydrogen peroxide (1.2 equiv.) as oxidant proved to be effective for amination of benzoxazoles, benzothiazoles, and 2-phenyl-1,3,4-oxadiazole [95]. It is worth noting that in amination of benzoxazoles with secondary aliphatic amines the cobalt catalyst provides better results, while the manganese catalyst is more effective for a similar reaction with primary alkylamines and ammonia. Also the reactions of benzoxazoles with secondary aliphatic amines or formamides have been performed successfully with Cu(OAc)2 (20 mol.%) and oxygen as oxidant [96]. Other azoles do not react with primary alkylamines in the presence of this oxidant. In contrast, when FeCls was used in 0.25-1 equiv. amounts, amination of benzoxazoles and 2-aryl-1,3,4-oxadiazoles (with the exception of their nitro derivatives) proved to... 

Scheme 39 Acid-promoted oxidative amination of benzoxazole...

Amination of benzoxazoles and 1,3,4-oxadiazoles with secondary amines in the presence of Brpnsted or Lewis acid and 2,2,6,6-tetramethylpiperidine-Af-oxoammonium tetrafluoroborate (TEMPO BF4 ) as oxidant has also been reported [99]. The reaction is supposed to proceed via the acyclic amidine intermediate, which is converted into the corresponding 2-aminoazole through stepwise... 

Scheme 41 Metal-free two-step amination of benzoxazoles and 1,3,4-oxadiazoles...

Scheme 45 Proposed mechanism for iodide-catalyzed amination of benzoxazoles...

Also it should be noted that a very specific kind of the ANRORC transformations have been mentioned in the previous section, when discussing oxidative amination of benzoxazoles and 1,3,4-oxadiazoles (Sect. 4, Schemes 41 and 42). 

Scheme 66 Co- and Mn-catalyzed direct amination of benzoxazoles with primary and secondary amines.

Scheme 67 Proposed mechanism for the Co-catalyzed direct amination of benzoxazoles.

Tetrabutylammoniumiodide-catalysed amination of benzoxazoles by substituted amines to form 2-aminobenzoxazoles in excellent yields of up to 93%, using aqueous solutions of H2O2 or TBHP as co-oxidant, has been attributed to in situ iodination of the secondary amine. 

Direct Amination of Azoles, Decarbonylative amidation and amination of benzoxazole andbenzothiazole couldbe achieved using a Pd VAg system, promoted by carboxylic acid additives. Silver(I) fluoride performed inferiorly to Ag2C03 (30 vs. 78%). Stoichiometric amounts of silver salt were required to maximize reactivity no reaction occurred using only catalytic silver. Silver is postulated to help rearomatize the heteroarene following amination. Diversely substituted benzoxazoles and benzothiazoles afforded the C2-aminated product in moderate to excellent yield (eq 18). 

Soon after, Xue s group also demonstrated a visible-light photocatalytic transformation of chloroamines to nitrogen-centered radicals. This strategy was utilized for the direct C-H amination of benzoxazoles in a one-pot, two-step process (Eq. (13.27)) [76]. This one-pot process circumvents the needs for purification of the chloroamines, showing the potential of this amination for synthetic applications. 

In contrast with the hitherto described silylation-aminations of six-membered heterocycles, silylation-amination of five-membered hydroxy-N-heterocycles such as benzoxazol-2-one 289 with excess benzylamine and HMDS 2, to give 2-benzyla-minobenzoxazole, fails, because of the equilibrium between 2-trimethylsilyloxy-... 

Silylation-amination fails with 5-ring-hydroxy-N-heterocycles such as 2-benzoxazolone since, at temperatures of I30°C, the 2-trimethylsilyloxy-benzoxazole (190) is in equilibrium with its open form 191 (73LA772), which reacts readily with benzylamine to eventually form N,N -dibenzylurea (CftHjCHj—NH-CO—NH—CH2C6H5). The silylation-amination procedure has been applied to the amination of 6-oxadihydro-uracil (193) with benzylamine to 194 (77JMCI34). The 5-deazapteridine derivative 195 affords, with ammonia/HMDS in the presence of p-toluenesulfonic acid, the diaminated product 1% in 74% yield (86JMC709). 

The complex reaction of dimethyl acetylenedicarboxylate with 2-methyl-benzoxazole in ethanol yields, inter alia, the benzoxazoloazepine (427), Both the S- and the A -acyl derivatives of benzoxazole-2-thione are effective acylating agents for amines and alcohols. ... 

Benzoxazoles are classically created through the cyclization of a 2-aminophenol with a carboxylic acid under highly acidic conditions at elevated temperatures. Alternatively, the amine of a 2-aminophenol is acylated and subsequently subjected to a number of cyclodehydration... 

A metal-free protocol for amination of azoles has recently been reported [98]. It includes two steps (1) the ring opening of benzoxazoles or oxadiazoles on heating with secondary aliphatic amines and (2) oxidative ring closure of the resulting amidines on their treatment with (diacetoxyiodo)benzene as oxidant within a short time at room temperature (Scheme 41). The same process can also be performed as a one-pot synthesis without isolation of the amidine intermediate. 

Benzoxazoles have also been aminated with secondary or primary aliphatic amines (1 equiv.) in the presence of catalytic amount of iodine (5 mol%), aqueous f-butyl hydroperoxide (1 equiv.), and acetic acid (1.1 equiv.) at ambient temperature for 12 h [102]. Authors believe that protonation of benzoxazole results in the formation of equilibrium amount of the salt 69, which adds alkylamine to form 2-aminobenoxazoline 70 (Scheme 46). Interaction of 70 with iodine generates 2-amino-3-iodobenzoxazoline 68, which eliminates HI to give the amination product. The reaction cycle is maintained due to oxidation of iodide ions with t-BuOOH. It is important to note that this envirorunentally benign method produces tertiary butanol and water as by-products. Use of iV-iodosuccinimide catalyst in combination with aqueous hydrogen peroxide in acetonitrile solution allows to reduce the reaction time to 4 h [103]. Benzothiazole under the same conditions remaines unchanged. 

Further elaborations/modifications of the oxazole ring were also described. For example, a new POCN-pincer palladium catalyst was used in the copper-mediated arylation of the C-2 position of benzoxazoles and oxazoles with aryl iodides in satisfactory yields (14DT16084). An original method for the direct amination of heteroarenes including benzoxazoles was reported involving a one-pot heteroarene C-H zincation followed by a copper catalyzed electrophilic amination (14AGE4667). 

A silver-mediated amination reaction of benzoxazoles (100 134) (Scheme 65) was reported by Chang under relatively mild conditions (60 °C, 0.8—1.0 eq. amine) compared to earlier reports (140 °C, 4 eq. amine (Mori) and 120—140 °C, 5 eq. amine (Schreiber)) (2009AGE9127). 

Lahm G, Opatz T (2014) Unique regioselectivity in the C(sp )-H oi-alkylation of amines the benzoxazole moiety as a removable directing group. Org Lett 16 42014-203... 

Figure 2.19 A cross-section of results for the copper-catalyzed amination of aryl halides with nitriles to give amides and benzoxazoles via in situ hydrolysis, by Xiang et al. [89].

In an alternative to Buchwald-Hartwig aminations, obviating the need for reactive aryl halides, sulfonates, expensive palladinm catalysts and ligands, Li, Dean et al. have recently described the successfnl amination of substituted benzoxazoles in the 2-position, with a range of secondary amines. Their optimized conditions used Ni(OAc)2 4H2O as catalyst with TBHP as oxidant, propionic acid in aceto nitrile. 

The use of perfluoroanilines for the synthesis of benzoxazoles having fully fluo-rinated benzene ring was demonstrated [55], Pentafluoroaniline has amine nitrogen... 

Aromatic hydrocarbons, aromatic amines, nitriles, benzoxazoles and isocyanates which correspond to partial fragments of the polymer main chain. 

Very recently, Gu, Li, and coworkers described an iron-catalyzed tandem oxidative process for the synthesis of benzoxazoles from easily available substrates, in which an alkyl C(sp )-H bond adjacent to an oxygen atom was directly aminated with a N-H bond (Scheme 9.9) [11]. In addition, excellent functional group tolerance under relatively mUd conditions and great regioselectivity were exhibited. 

Scheme 9.9 Synthesis of Benzoxazoles by Tandem C(sp )-H Oxidative Amination.

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