Mechanism of the Reaction of Lawesson’s Reagent with N‐Alkylhydroxamic Acids

Abstract

The mechanism of the reaction under discussion has been established by investigating the products of the reaction between 2,4‐bis(4‐methoxyphenyl)‐1,3,2,4‐dithiadiphosphetane 2,4‐disulfide (Lawesson’s reagent, LR) and N‐alkylhydroxamic acids HAs 1. The primary intermediate is an adduct, O‐dithiophosphonylated hydroxamic acid 19, which decomposes to yield metathiophosphonate (AnsPOS), a sulfur atom, and an amide. At the same time, owing to the co‐existence of 19 and metadithiophosphonate (AnsPSS) in equilibrium, the carbonyl group is thionated. It has also been established that monomeric AnsPOS formed in both reduction and thionation processes does not undergo oligomerisation to cyclic trimer 5 and linear oligomers, which is typical for amides reacting with LR. Since there is unreacted HA 1 in the reaction mixture, AnsPOS takes part in a controlled transformation to form a dimer, the corresponding pyrothiophosphonate 3, together with the intermediate O‐thiophosphonylated hydroxamic acid 2. A hydrolysed product of AnsPOS, namely (4‐methoxyphenyl)thiophosphonic acid 4, participates in the last reaction. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Lawesson's reagent for direct thionation of hydroxamic acids: Substituent effects on LR reactivity

“…Amides are better nucleophiles and therefore react with LR much faster than esters, but the effect of substituents on the thionation rate of amides has never been studied [10]. In the previous report [8], it was found that EWG-substituted HAs give better yields of the corresponding THAs 2. It can be assumed that this effect results from both lower nucleophilicity and stronger N O bond of EWG-substituted HAs as compared with EDG-substituted ones.…”

“…NMethyl-, N-tert-butyl-and N-benzylhydroxylamine hydrochlorides were obtained from Aldrich. Hydroxamic acids 1Aa [14], 1Ab [15], 1Ac [16], 1Ad [17], 1Ae-1Af [18], 1Aj-1Ak [19], 1Al [20], 1Am [21], 1An [22], 1Ba [23], 1Bb-1Bc [24], 1Bd [25], 1Be [26], 1Bf [8], 1Bh [8], 1Bk [7], 1Bo [8], and 1Bu [27] are known compounds and were synthesized according to general procedure described below. Thiohydroxamic acids 2Bh, 2Bi, 2Bm, 2Bo, and 2Bp were prepared and characterized previously [11].…”

“…Furthermore, we proved the coexistence of four independent processes: two parallel-the benzohydroxamic acid thionation (T 1 ) and deoxygenation (R 1 ) pathways-and two subsequent steps involving reduction of benzothiohydroxamic acid 2B (R 2 ) and thionation of benzamide 3B (T 2 ). Also the mechanism of LR action on HAs 1 was proposed [8]. According to the suggested mechanism, anisyldithiophosphorane (AnsPSS) generated from LR attacks the hydroxyl group of HA 1 yielding an elusive adduct, the O-dithiophosphonylated HA 1-PSSH.…”

Phosphorus substituted hydroxylamine and hydroxamic acid derivatives: synthesis and reactivity

“…Direct thionation of hydroxamic acids with Lawesson´s reagent (LR) 142 can be very useful in the synthesis of thio analogues of natural hydroxamates and N-hydroxythiopeptides. 55 …”

On the reaction of bis(phosphothioyl)disul‐fanes with hydroxamic acids, part I: Ionic versus radical reaction pathways

“…Only one patent deals with the preparation of N-methyl-N-diethoxyphosphinthioyloxy acetamide starting from N-chloro-N-methylacetamide in moderate yield [10]. Recently, we isolated N-isopropyl-N-[methoxy) (4-methoxyphenyl)phosphinothioyloxy]benzamide from the reaction mixture of the corresponding hydroxamic acid and Lawesson's reagent (LR) [11].…”