Benzotriazoles, acyl, acylating

H-l,2,3-Benzotriazole, 2-phenyl-oxidation, 5, 721 as photostabilizers, 5, 731 synthesis, 5, 722 Benzotriazoles acylation, 5, 54 antifogging agents... 

In peptide syntheses, where partial racemization of the chiral a-carbon centers is a serious problem, the application of 1-hydroxy-1 H-benzotriazole ( HBT") and DCC has been very successful in increasing yields and decreasing racemization (W. Kdnig, 1970 G.C. Windridge, 1971 H.R. Bosshard, 1973), l-(Acyloxy)-lif-benzotriazoles or l-acyl-17f-benzo-triazole 3-oxides are formed as reactive intermediates. If carboxylic or phosphoric esters are to be formed from the acids and alcohols using DCC, 4-(pyrrolidin-l -yl)pyridine ( PPY A. Hassner, 1978 K.M. Patel, 1979) and HBT are efficient catalysts even with tert-alkyl, choles-teryl, aryl, and other unreactive alcohols as well as with highly bulky or labile acids. 

Azoles containing a free NH group react comparatively readily with acyl halides. N-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (66) -> (67) or type (70)->(71) or (72). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. When two isomeric products could result, only the thermodynamically stable one is usually obtained because the acylation reactions are reversible and the products interconvert readily. Thus benzotriazole forms 1-acyl derivatives (99) which preserve the Kekule resonance of the benzene ring and are therefore more stable than the isomeric 2-acyl derivatives. Acylation of pyrazoles also usually gives the more stable isomer as the sole product (66AHCi6)347). The imidazole-catalyzed hydrolysis of esters can be classified as an electrophilic attack on the multiply bonded imidazole nitrogen. 

The reaction also proceeds readily with A/-monosubstituted 1,2-diaminobenzenes (6.45, R = alkyl, aryl, acyl). Kroupa and Matrka (1970) investigated optimal reaction conditions for the synthesis of 1,2,3-benzotriazole from 1,2-diaminobenzene. 

A synthesis of 5-(aioylamino)-2-aryloxazoles 39 is outlined in Scheme 9. Heating the glycol 37 (Bt = benzotriazol-l-yl), prepared from glyoxal and benzotriazole, with an amide in the presence of an ion exchange resin yields the acylated diamine 38, which cyclises by the action of sodium hydiide in DMF <95JHC1651>. 

This reagent combination also converts carboxylic acids to acyl chlorides (see Section 3.4.1). The mechanistic basis for the special effectiveness of benzotriazole has not yet been determined, but it seems likely that nucleophilic catalysis is involved. Sulfinyl ester intermediates may be involved, because Z-2-butene-l,4-diol gives a cyclic sulfite ester with one equivalent of reagent but the dichloride with two equivalents. 

Treated with trifluoroacetic anhydride, sulfoxides 218 undergo conversion to triazapentalenes 219 with high yields. The process must involve acylation of the sulfoxide oxygen atom and generation of a carbocation that attacks the N-2 atom of benzotriazole. Hydrogenation over Raney nickel cleaves the C-S and one of the N-N bonds to generate >rtfe -substituted anilines 220 (Scheme 27) <2002EJ0493>. 

A wide range of A-acylbenzotriazoles 915 have been prepared under mild conditions in reactions of carboxylic acids with thionyl chloride in the presence of fourfold excess of benzotriazole, including R = alkyl, a-haloalkyl, a-alkoxyalkyl, alkenyl, alkinyl, aryl, and heteroaryl <2003S2795, 2004RQM275>. They represent convenient acylating agents for variety of nucleophiles. Synthetic applications of such compounds have been reviewed <2005SL1656>. 

Carbonyl oxygen atoms of aldehydes can also be efficiently acylated by 1-acylbenzotriazoles 915 in the presence of mild bases (K2CO3, Et3N). The released benzotriazolide anions are consecutively attached to the aldehyde carbonyl carbon atoms to produce esters 944 (Equation 20). Aliphatic aldehydes react quickly at room temperature, but aromatic aldehydes require elevated temperatures. The yields are good to quantitative. The amounts of benzotriazol-2-yl isomers of esters 944 in the products mixtures is strongly dependent on the reaction conditions and the character of groups R1 and Rz, and it may vary from 5% to 25% <1999JHC777>. 

Treated with a base, l-(arylacetyl)benzotriazoles 954 eliminate benzotriazole to form ketenes 955. When no other reagent is added, ketene 955 is acylated by another molecule of 954 to produce ot-ketoketene 956 which upon addition of water and decarboxylation during the work-up is converted to symmetrical dibenzyl ketone 957... 

Each of the routes discussed thus far in this section are reliant upon amidoxime-based methods. In a change from this paradigm, Makara etal. produced the polymer-supported benzotriazoles 294 and converted them easily into the iV-acyl-177-benzotriazole 1-carboximidamides 295. Cyclization with hydroxylamine gave the supported 3-amino-l,2,4-oxadia-zoles 296 which were cleaved with TFA to give the free 3-amino-l,2,4-oxadiazoles 297 (Scheme 49) <2002TL5043>. 

Reactions of (benzotriazol-l-yl)carboximidamides and acyl- or arylamino-carbonyl(benzotriazol-l-yl)carboximidamides with hydrogen sulfide give the corresponding thioureas and tV-acylthioureas or tV-carbamoylthioureas, respectively (Scheme 47).128... 

Acylbenzotriazoles 162 are efficient C-acylation reagents for the regioselective conversion of ketone enolates into P-diketones . Diethyl(l-benzotriazolmethyl)phosphinate (163) was found to be a convenient reagent for the stereoselective preparation of (E)-l-(l-alkenyl)benzotriazoles <00SC1413>. The novel three-carbon synthon 1-(1//-133-... 

Benzotriazole has been prepared directly by the action of nitrous acid on 0-phenylenediamine1 and by the hydrolysis of an acylated or aroylated benzotriazole which has been previously prepared by the action of nitrous acid on the corresponding mono acylated or aroylated 0-phenylenediamine.2 3 4-i The above procedure is the direct method and gives better over-all yields than the methods involving several intermediate steps. Most methods described in the literature employ mineral acid. Acetic acid is much more satisfactory. 

Benzotriazoles are neutral acylating agents, successfully used for the preparation of amides, oxamides and hydrazides The acylbenzotriazoles 95a-d are prepared from carboxylic acids 94a-d by reaction with l-methanesulfonyl-l//-benzotriazole (Scheme 51). Reaction of 1-benzoyl-l//-benzotriazole with hydroxylamine hydrochloride in the... 

The isomerization between N- and (9-acylated benzotriazol-l-ols and 1,2,3-triazol-l-ols has been extensively studied (see Section 4.01.7.1) in part by x-ray methods. The aroyl group position is established by x-ray crystallographic analyses because the N- and (9-acylated forms are not readily distinguished by spectral methods. X-ray analyses of l-(4-nitrobenzoyloxy)-1,2,3-triazole (19a) <93AX(C)49>, l-(4-chlorobenzoyloxy)-l,2,3-triazole (19b) <88AX(C)1063>, and 1-benzoyloxy-... 

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