Direct Synthesis of Esters and Amides from Unprotected Hydroxyaromatic and -aliphatic Carboxylic Acids

Abstract

A facile method for the activation of hydroxy-substituted carboxylic acids using benzotriazole chemistry without prior protection of the hydroxy substituents is presented. The N-acylbenzotriazole intermediates 2a-g, 6a-d, and 9a-c have been used for high-yielding synthesis of both aliphatic (3a-l) and aromatic (7a-h, 10a-f) hydroxy carboxamides. High yields of aromatic hydroxy esters 12a-h and 13a-i were obtained using either neat alcohols in neutral microwave conditions or nucleophilic alkoxides and the intermediate N-(arylacyl)benzotriazoles. Moderate yields were obtained in the case of aliphatic hydroxy esters 11a,b and thiolesters 11e-g from the intermediates 2a-c.

Efficient synthesis of 1,3-benzodioxin-4-one and benzoxazine-2,4-diones

“…Crystalline N-(o-hydroxyarylacyl)benzotriazoles 4a-c or 6a-c isolated from corresponding salicylic acids, 37 were treated with 4 equivalents of the appropriate aromatic or aliphatic aldehyde in dry THF at room temperature along with 4 equivalents of triethyl amine to give 1a-d and 7a-c respectively in high yields (Scheme 4 and Table 1). Best results were obtained when the base was added to a well stirred mixture of aldehyde and acylbenzotriazoles 4a-c or 6a-c.…”

“…The compounds 4a-c and 6a-c were synthesized as reported. 37 General procedure for the synthesis of 1,3-benzodioxin-4-ones 1a-d and naphtho-1,3-dioxinones 7a-c The appropriate aldehyde (3 eq) was added to N-(o-hydroxyarylacyl) benzotriazoles 4a-c / 6a-c (1mmol) in freshly dried THF (4 mL) under inert atmosphere. The mixture was stirred for 5 min before addition of triethylamine (3 eq).…”

“…[34][35][36] Recently, we utilized the N-(o-hydroxyarylacyl)benzotriazoles for the syntheses of o-hydroxyaroyl esters / amides (Scheme 3). 37 Herein we report the successful use of the N-(o-hydroxyarylacyl)benzotriazoles 4 and 6 as substrates for the synthesis of 1,3-benzodioxin-4-ones 1, 7 and benzoxazine-2,4-diones 2, 9 (Scheme 4 and Tables 1, 2). …”

Synthesis of Nα-protected amino/peptide Weinreb amides employing N,N'-carbonyldiimidazole as activating agent; studies on docking and antibacterial activities

“…They are selectively reduced to aldehydes using LiAlH4 and form ketones upon reaction with Aromatic amides and esters have been synthesized by in situ activation of hydroxy acids using CDI mediated coupling. 20 N,N′-carbonyldiimidazole is one of several universally used reagents for the activation carboxyl groups. It is relatively cheap and the byproducts are carbon dioxide and imidazole.…”

A new protocol for the synthesis of primary, secondary and tertiary anthranilamides utilizing N-(2-aminoarylacyl)benzotriazoles

“…They are widely employed in heterocyclic synthesis, 13a,b N-acylation, 14a-c Cacylation, 14b,15a,b S-acylation 14b,16a,b and O-acylation. 17 Unlike the conventional acylating agents which are unstable to moisture and difficult to prepare and store at room temperature, Nacylbenzotriazoles are stable crystalline compounds and they are easy to use and store at room temperature. 14a, 18 They can be prepared directly from carboxylic acids even in cases where an acid sensitive functionality is present.…”