Acyl derivatives anhydrides

Azlactones (anhydrides of a-acylamino acids) are formed by the condensation of aromatic aldehydes with acyl derivatives of glycine in the presence of acetic anhydride and anhydrous sodium acetate. Thus beiizaldehyde and acetyl-... 

It will be observed that the reaction involves two equivalents of the amine and produces, in addition to the substituted amide, an equivalent quantity of the amine hydrochloride. Acetic anhydride, on the other hand, converts the amine quantitatively into the acyl derivative, for example ... 

Isoquinoline can be reduced quantitatively over platinum in acidic media to a mixture of i j -decahydroisoquinoline [2744-08-3] and /n j -decahydroisoquinoline [2744-09-4] (32). Hydrogenation with platinum oxide in strong acid, but under mild conditions, selectively reduces the benzene ring and leads to a 90% yield of 5,6,7,8-tetrahydroisoquinoline [36556-06-6] (32,33). Sodium hydride, in dipolar aprotic solvents like hexamethylphosphoric triamide, reduces isoquinoline in quantitative yield to the sodium adduct [81045-34-3] (25) (152). The adduct reacts with acid chlorides or anhydrides to give N-acyl derivatives which are converted to 4-substituted 1,2-dihydroisoquinolines. Sodium borohydride and carboxylic acids combine to provide a one-step reduction—alkylation (35). Sodium cyanoborohydride reduces isoquinoline under similar conditions without N-alkylation to give... 

Acetylsucrose [63648-81-7] has been prepared in 40% yield by direct acetylation of sucrose using acetic anhydride in pyridine at 40° C (36). The 6-ester has subsequently been obtained in greater than 90% yield, by way of 4,6-cycHc orthoacetate. Other selective methods for the 6-acylated derivatives include the use of alkyl tin reagents such as dibutyl tin oxide (37) and of dibutyl stannolane derivatives (38). Selective acetylation of sucrose by an enzymic process has also been described. Treatment of sucrose with isopropenyl acetate in pyridine in the presence of Lipase P Amano gave, after chromatography, 6-0-acetylsucrose (33%) and 4/6-di-O-acetylsucrose (8%). The latter compound has been obtained in 47% yield by the prolonged treatment (39). 

Organic Acids and Their Derivatives (Anhydrides, Nitriles, Ureas). Alkyleneamines react with acids, esters, acid anhydrides or acyl hahdes to form amidoamines and polyamides. Various diamides of EDA are prepared from the appropriate methyl ester or acid at moderate temperatures (25,26). 

As noted above, the steroid nucleus has been a favorite for the design for site directed alkylating antitumor drugs. Thus reaction of prednisolone (62) with anhydride 63 affords the 21 acylated derivative, prednimustine (64). ... 

This chapter covers not only nuclear and extranuclear quinoxahnecarboxylic acids (and anhydrides) but also the carboxylic esters, acyl halides, carboxamides, carbohydrazides, carbonitriles, carbaldehydes, and (ketonic) acyl derivatives of quinoxaline a few related speceis are also included. To avoid repetition, the interconversions of these quinoxaline derivatives are discussed only at the first opportunity thus the esterification of quinoxalinecarboxylic acids in covered as a reaction of carboxylic acids rather than as a preparative route to carboxylic esters, simply because the section on carboxylic acids precedes that on carboxylic esters. To minimize any confusion, appropriate cross-references have been inserted. 

Tertiary alkyl azides can be prepared by stirring tertiary alkyl chlorides with NaN3 and ZnCl2 in 82 ° or by treating tertiary alcohols with NaN3 and CF3-COOH or with HN3 andTiCl4 or BF3. Acyl azides, which can be used in the Curtius reaction (18-14), can be similarly prepared from acyl halides, anhydrides, " esters, or other acyl derivatives. ° Acyl azides can also be prepared... 

The best reagent for the double acyl derivative (3) is the anhydride (4) whose synthesis is discussed in Chapter T 17. Reaction of (4) with ammonia gives TM (1). 

In addition to acyl halides and acid anhydrides, there are a number of milder and more selective acylating agents that can be readily prepared from carboxylic acids. Imidazolides, the (V-acyl derivatives of imidazole, are examples.115 Imidazolides are isolable substances and can be prepared directly from the carboxylic acid by reaction with carbonyldiimidazole. 

Reactions of Organozinc Reagents with Acyl Halides, Anhydrides, and Other Carboxylic Acid Derivatives... 

Anhydrides, such as acetic anhydride (Sections 4.2 and 5.1, this chapter), may react with carbohydrate hydroxyls even in aqueous environments to form acyl derivatives. The reaction, however, is reversible by incubation with hydroxylamine at pH 10-11. 

Azido derivatives of furazans have proved to be particularly useful for the synthesis of heterocyclic systems. Thus, by 1,3-dipolar addition of l-azido(4-amino-l,2,5-oxadiazol-3-yl)aldoxime 186 to propargyl alcohol and phenylacetyl-ene, bicyclic 4-amino-l,2,5-oxadiazol-3-yl(4-R-l,2,3-triazol-l-yl)ketoximes 187 were obtained (Equation 34) which in reaction with acetic anhydride afforded the corresponding 0-acyl derivatives <2003RJ0574>. 

The 5-amino-1,2,4-thiadiazolidine 29 can be acylated with acetic anhydride in pyridine at N-2 to give the iV-acyl derivative 30 (Equation 7) <1998JHC1435>. 

N-Acylation. Acyl chlorides or carboxylic anhydrides, which generally have a hard electrophilic character, can selectively convert OZTs into IV-acylated derivatives.59... 

The reaction of 3-pyrrolylaminomethylenemalonate (1500, R = H) and acetic anhydride at reflux temperature for 1 hr gave (l-acetyl-3-pyrrolyl)aminomethylenemalonate (1500, R = Ac) in 81% yield. When 1500 (R = H) was acylated with acyl chlorides in a mixture of pyridine and THF at reflux temperature for 2-4 hr, the 5-acyl derivatives (1501) were obtained in 51-67% yields (85JHC817). 

The acylation of 6-indazolylaminomethylenemalonate (1470) by reaction with acetic anhydride in the presence of pyridine for 45 min, or with benzoyl chloride in a mixture of DMF and benzene in the presence of sodium ethylate for 75 min, gave 1-acyl derivatives (1504) in 72% and 58% yields, respectively (78YZ1158). 

A method involving SPE was developed for the determination of ten A-nitroso amino acids in cured meat products. These compounds were derivatized with diazomethane followed by O-acylation of hydroxyl groups with acetic anhydride-pyridine reagent. The methyl esters and their acylated derivatives were separated by GC on a DB-5 fused silica capillary column and quantified with a TEA-CLD specific for the nitric oxide derived from the thermal denitrosation of nitrosamines recovery exceeded 75% at the 10 ppb level579. 

Reaction of 98 with a variety of acid anhydrides in the presence of pyridine produced a series of 4-acyl derivatives (A) in which only the group at C-4 varies (Scheme 4, Table X). By reacting the chloroacetyl derivative (A, R = CHjCI) with various amines, a series of 4- (a-aminoacyl) derivatives (B) were prepared. 

Nohira et al. treated N-acylamino acids 195 with thionyl chloride mixed anhydrides 196 were formed below 30°C. The latter compounds gave the first type of hexahydro-2//-3,l-benzoxazin-4-one 197 on triethylamine treatment [77H(7)301]. This reaction was also performed with diexo- and diendo-substituted j8-amino acids 198 yielded the 5,8-methano-2//-3,l-benzoxazin-4-ones 199 via the acyl derivatives 200 (84S345,84T2385). Further homologs were also prepared by the dehydration of N-acylamino acid derivatives (85MI1 88MI3). 

Nucleophilic attack at sulfur is implicated in many reactions of 1,2,4-thiadiazoles <84CHEC-I(6)463> and in general soft nucleophiles attack at sulfur. For example, reaction of 3-hydroxy-5-phenyl-1,2,4-thiadiazole (23) with acetic anhydride in the presence of dbu at 130°C gives the thiazoles (31) and (32) <85JHC1497>. These products may be reasonably explained by the mechanism outlined in Scheme 9 in which the thiadiazole ring is opened by the acetic anhydride carbanion. There is some evidence that (32) may arise from attack of the carbanion on the A-acylated derivative (30a) (Scheme 9) <85JHC1497>. 

It was shown previously that saturated 5(4//)-oxazolones or 2-oxazolm-5-ones with only one substituent at C-4 can be considered as the tautomeric form of saturated 5(2//)-oxazolones or 3-oxazolin-5-ones. These compounds can also be considered as amino acid derivatives and, indeed, cyclization procedures are the most commonly used to prepare these compounds. The cyclization reaction employs a variety of cyclodehydrating agents and the general method is shown in Scheme 7.23, with an A-acyl-a-amino acid being the most typical starting material used. In this way, 5(4//)-oxazolones derived from most natural amino acids 99 (R3 = H) have been obtained by heating the corresponding A-acyl derivatives in the presence of acetic anhydride. 

Many such activated acyl derivatives have been developed, and the field has been reviewed [7-9]. The most commonly used irreversible acyl donors are various types of vinyl esters. During the acylation of the enzyme, vinyl alcohols are liberated, which rapidly tautomerize to non-nucleophilic carbonyl compounds (Scheme 4.5). The acyl-enzyme then reacts with the racemic nucleophile (e.g., an alcohol or amine). Many vinyl esters and isopropenyl acetate are commercially available, and others can be made from vinyl and isopropenyl acetate by Lewis acid- or palladium-catalyzed reactions with acids [10-12] or from transition metal-catalyzed additions to acetylenes [13-15]. If ethoxyacetylene is used in such reactions, R1 in the resulting acyl donor will be OEt (Scheme 4.5), and hence the end product from the acyl donor leaving group will be the innocuous ethyl acetate [16]. Other frequently used acylation agents that act as more or less irreversible acyl donors are the easily prepared 2,2,2-trifluoro- and 2,2,2-trichloro-ethyl esters [17-23]. Less frequently used are oxime esters and cyanomethyl ester [7]. S-ethyl thioesters such as the thiooctanoate has also been used, and here the ethanethiol formed is allowed to evaporate to displace the equilibrium [24, 25]. Some anhydrides can also serve as irreversible acyl donors. 

---