Mannich‐type condensation reactions of sulfinic acids with aldehydes and nitrogen bases: Part. VI. The use of ureas, thioureas and thiobenzamide

Abstract

Urea, thiourea and some N′‐alkyl(di)substituted ureas and thioureas were found to react as the amine component in Mannich‐type condensation reactions with p‐toluene‐ or phenylmethane‐sulfinic acid and aldehydes. Mono‐ or di‐alkylation products are formed in good yields depending on the N′‐ and N′‐substituents in the substrate, while N,N,N′‐trimethylurea or ‐thiourea failed to react. N′‐Hydroxy‐N′‐phenylthiourea is alkylated on the N′‐atom bearing the OH‐substituent as demonstrated by the ESR spectrum of the thioacyl nitroxide derived from the condensation product. Thiobenzamide, in contrast with thioacetamide, also condensed with p‐toluenesulfinic acid and formaldehyde or N′‐butyraldehyde. With benzaldehyde, however, Mannich‐type condensation did not occur and 3,5‐diphenyl‐1,2,4‐thiadiazole was isolated instead. The NMR spectra of several urea and thiourea condensation products provided evidence for hindered internal rotation in the urea and thiourea function and some ΔG≠ values for the exchange process were estimated. Intramolecular shielding effects were observed in the NMR spectrum of 4c and 4f indicating the occurrence of folded conformations.

α-Amido Sulfones as Stable Precursors of ReactiveN-Acylimino Derivatives

“…The three-components coupling leading to the synthesis of α-amido sulfones was pioneered by Engberts and Strating who in 1964 obtained a number of these sulfones by mixing ethyl carbamate, formaldehyde, and sodium sulfinates in acidic conditions . Later on, the same authors prepared several amidosulfonyl derivatives 14 starting from suitable nitrogenated compounds 11 , alkyl or aryl aldehydes 12 , and sodium sulfinates 13 (Scheme and Table ). −

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“…39 Later on, the same authors prepared several amidosulfonyl derivatives 14 starting from suitable nitrogenated compounds 11, alkyl or aryl aldehydes 12, and sodium sulfinates 13 (Scheme 3 and Table 1). [40][41][42][43] The obtained sulfones 14 are mostly stable solids that often precipitate from the reaction mixture and are easily recovered by a simple filtration. The classical procedure usually gives poor results when formamide is used to prepare sulfones 14; 44,45 however, a slight modification in the reaction conditions allows a proper preparation of these amido derivatives.…”

Organocatalysis by Networks of Cooperative Hydrogen Bonds: Enantioselective Direct Mannich Addition to Preformed Arylideneureas

“…Unfortunately, the application of the reported methodology to common aldehydes was not successful. Therefore, we investigated a viable synthesis of 1 by recourse to the standard two‐step methodology for accessing N ‐acyl imines via α‐ureidosulfone intermediates 2 . The treatment of compounds 2 with dried cesium carbonate led to the formation of aryl‐ and heteroarylideneureas 1 a – j as solids, which were stable for up to 7 days if kept dry in the cold under an inert atmosphere (Scheme )…”

“…[15] To the best of our knowledge,a rylideneureas 1 have not been prepared or described previously, [16] with one exception. [19,20] Thet reatment of compounds 2 with dried cesium carbonate led to the formation of aryl-and heteroarylideneureas 1a-j as solids, which were stable for up to 7days if kept dry in the cold under an inert atmosphere (Scheme 2). Therefore,weinvestigated aviable synthesis of 1 by recourse to the Scheme 1.…”

1-(N-Acylamino)alkyl Sulfones from N-Acyl-α-amino Acids or N-Alkylamides

“…The most frequently used method for the synthesis of 1-( N -acylamino)alkyl sulfones 3 , pioneered by Engberts and Strating in 1964, consists of three-component condensation of primary amides, carbamates, or carbamides ( 1 , R 1 = R, OR, or NHR, respectively) with aldehydes 2 and sodium sulfinates (Scheme ). − O - or S -Thiocarbamates, dithiocarbamates, or thiocarbamides have also been applied in a similar reaction. , Other methods for synthesizing these compounds, such as oxidation of the corresponding sulfides with H 2 O 2 , KMnO 4 , or m CPBA, − the Curtius-type rearrangement of α-sulfonylacyl azides, and substitution of the chlorine anion in N -(1-chloroalkyl)amides with p -toluenesulfinic acid, have found only limited application . The structural diversity of 1-( N -acylamino)alkyl sulfones synthesized using the Engberts and Strating method is confined by the limited availability of structurally diverse aldehydes 2 .…”