Monoacyl derivative preparation

B). The monoacyl derivatives of N,N-dioctadecyl-l,3-propanediamine are prepared as follows ... 

Dimethyl-188 and 2,6-dimethylpyrazine react very similarly to methylpyrazine. Thus, 2,6-dimethylpyrazine can be converted into a monoanion with sodamide in liquid ammonia which can be condensed with aldehydes and ketones,179 acylated with esters,181 and alkylated with alkyl halides181 to give the corresponding 2-methyl-6-substituted pyrazines. Acylation under suitable conditions also yields diacylated derivatives. Thus, when 2,6-dimethylpyrazine, sodamide, and ethyl benzoate are reacted in 1 3 2 molecular proportion, 38% 2,6-diphen-acylpyrazine (35) and 25% 2-methyl-6-phenacylpyrazine (36) is obtained. From the preparative point of view it is better to form the diacyl derivative by the further acylation of the monoacyl derivative rather than by direct diacylation.187... 

Amino-l,2,4-thiadiazoles (16) readily yield monoacylated derivatives of type (129) under the usual conditions whereas both monoacyl and diacyl derivatives (130 and 131, respectively) are easily obtained from the 3-amino isomers (65AHC(5)119, 70CB1805). In a similar manner the 3-amino-l,2,4 thiadiazoles produce mono- and di-sulfenamide derivatives when treated with sulfenyl halides. In general, the reactions of 3-amino- and 5-amino-1,2,4-thiadiazoles with sulfonyl halides under basic conditions produce only low yields of the desired derivatives. Sulfonamides of type (132) are best prepared by ring synthesis methods as illustrated in Scheme 55 (75LA1961). 

Occasionally, benzimidazoles are made by cyclization of diacylatcd o-arylencdiamines (38) (Scheme 2.1.17). Ring closure of these compounds requires higher temperahires than for the monoacyl derivatives. They can, however, be cyclized in a melt, or in the presence of acid catalysts, and when conditions are anhydrous, 1-acylbenzimidazoles may be isolated. These latter compounds are azolides , and as such are prone to ready cleavage by nucleophiles. Mixtures of products are likely to be formed if the two acyl groups are different. For example, thermolysis of A/ -acetyl-A/ -benzoyl-o-phenylcnediamine gave a 3 1 mixture of 2-mcthyl- and 2-phenyl benzimidazoles [104]. A recent modification has been used to prepare 1-acetyl-2-mcthylbenzimidazole (39) in quantitative yield [ 105]. Compound (39) can,... 

Phospholipase B is known as monoacylphos-pholipase (lysophospholipase). Both 1-acyl and 2-acyl monoacyl derivatives of phosphatidylcholine and phosphatidylethanolamine are attacked. Unsaturated fatty acids are the preferred chains for attack (van den Bosch et al., 1968). Other synthetic compounds are also hydrolysed e.g. acyl ethylene-glycolphosphorylcholine (Dawson, 1973). Although the classic phospholipase B is prepared from Penicillium notatum, the enzyme from that source will, in fact, hydrolyse diacylphospholipids under certain conditions, and is therefore a phospholipase A (Kawasaki and Saito, 1973). 

Scheme 4 Top selective monoacylation of octyl p-D-glucopyranoside catalyzed by C2 symmetric PPY derivative 3. Bottom monoacylated pyranosides prepared using catalyst 3...

Eapen and Tamborski prepared few 2-perfluoroaIkylbenzimidazoles from o-phenylenediamine (Scheme 17) [27]. While 2-pentafluoroethyl- and 2-heptafluor opropylbenzimidazole were prepared by heating o-phenylenediamine with the corresponding acid anhydride and carboxylic acids, respectively, a benzimidazole bearing a perfluoroalkyl ether at C-2 was prepared in a two-step procedure via a A -monoacyl derivatives of o-phenylenediamine. Likewise, a bis(benzimidazole) was prepared by the condensation of o-phenylenediamine with 0.5 equivalent of diethyl 2,2,3,3,4,4-hexafluoropentanedioate. 

Support-bound 1,2-diamines can be readily converted into imidazolidinones by treatment with carbonyl diimidazole [128,129]. The required diamines have been prepared on cross-linked polystyrene by reduction of peptides bound to MBHA resin with borane. Similarly, bicyclic imidazolines have been prepared from triamines and thiocarbonyl diimidazole (Entry 10, Table 14.3). Dehydration of polystyrene-bound monoacyl ethylene-1,2-diamines yields 4,5-dihydroimidazoles (cyclic amidines, Entry 5, Table 13.18). Several groups have reported the synthesis of 2-aminoimidazol-4-ones from resin-bound amino acid derivatives (e.g., Entry 6, Table 15.11). Most of these compounds are, however, unstable, and slowly decompose if dissolved in DMSO (Jesper Lau, private communication). 

Asymmetric Diels-AUer reactions The observation that simple acyloxy-boranes such as H2BOCOCH=CH2, prepared by reaction of BH3 with acrylic acid, can serve as Lewis acid catalysts for reactions of the a,P-unsaturated acids with cyclopentadiene (15, 2) has been extended to the preparation of chiral acyloxy-boranes derived from tartaric acid. The complex formulated as 3, prepared by reaction of BH3 with the monoacylated tartaric acid 2, catalyzes asymmetric Diels-Alder reactions of a,P-enals with cyclopentadiene with high enantioselectivity. The process is applicable to various dienes and aldehydes with enantioselectivities generally of 80-97 % ee. 

Thermal dehydration of o- (acylamino)phenols is the method of choice for the preparation of benzoxazoles (equation 96) and other annulated oxazoles. 0,iV-Diacyl derivatives of o-aminophenols cyclize at lower temperatures than do the monoacyl compounds. The synthesis is often carried out by heating the aminophenol with the carboxylic acid or a derivative, such as the acid chloride, anhydride, an ester, amide or nitrile. The Beckmann rearrangement of oximes of o-hydroxybenzophenones leads directly to benzoxazoles (equation 97). 

The electronic effects of various substituents in the 6-position are pronounced enough to allow selective monoacylation. Thus 1,2,3,4-tetrahydro-6-nitroquinoxaline is exclusively monoacylated with acetic anhydride or trifluoracetic anhydride at the 4-position. The corresponding 1,4-diacylated derivatives are conveniently prepared by nitration of 1,4-diacetyl- and l,4-bistrifluoroacetyl-l,2,3,4-tetrahydro-quinoxaline, respectively." ... 

Initially, gem-diamines were prepared from iV-protected a-amino azide 14. Intermediate isocyanates 15 obtained by Curtius rearrangement of 14 were immediately trapped with a primary alcohol to afford the corresponding N,N -diacylated-1,1 -diaminoalkane derivatives 16, which were further de-protected to the monoacylated gem-diamine before coupling to carboxylic acids (Scheme 6) [125-128]. 

Although the first benzimidazole was prepared by Hobrecker in 1872, it was Ladenburg who extensively explored the preparation of benzimidazole derivatives by the condensation between ort/to-amino aniline and carbonyl compounds (aldehydes and ketones) in 1875. Subsequently, Phillips further extended Ladenburg s preparation to the condensation between ort/io-amino aniline and acetic acid to produce different kinds of carboxylic acids in the presence of dilute mineral acid. Therefore, the preparation of benzimidazole from ort/io-amino aniline is referred to as the Ladenburg method," Phillips method, Phillips modification, or the Phillips-Ladenburg reaction. It has been proposed that the condensation between ortho-dxaim aniline and carbonyl compounds involves the formation of a Schiff base intermediate," whereas the condensation between ort/io-amino aniline and acid proceeds via the A,lV -diacyl and monoacyl intermediated This condensation generally works for aliphatic acids and is feasible for aromatic acids if the condensations are carried out above 180°C in sealed reaction vessels. ... 

Monoacyl hydroquinone derivatives are, however, deacylated when treated with oxidizing agents (Ce, Tl, N-bromo-succinimide and bromine) [133, 134]. Thus the quinone (79) is prepared in high yield from the monoacetyl derivative (78) with AT-bromosuccinimide [135]. This method of deacylation is useful in the synthesis of quinones and the corresponding quinols. 

---