Untersuchungen über aromatische Amino‐Claisen‐Umlagerungen

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Abstract
Investigations on Aromatic Amino‐Claisen RearrangementsThe thermal and acid catalysed rearrangement of p‐substituted N‐(1′,1′‐dimethylallyl)anilines (p‐substituent=H (5), CH3 (6), iso‐C3H7 (7), Cl (8), OCH3 (9), CN (10)), of N‐(1′,1′‐dimethylallyl)‐2,6‐dimethylaniline (11), of o‐substituted N‐(1′‐methylallyl)anilines (o‐substituent=H (12), CH3 (13), t‐C4H9 (14), of (E)‐ and (Z)‐N‐(2′‐butenyl)aniline ((E)‐ and (Z)‐16), of N‐(3′‐methyl‐2′‐butenylaniline (17) and of N‐allyl‐(1) and N‐allyl‐N‐methylaniline (15) was investigated (cf. Scheme 3). The thermal transformations were normally conducted in 3‐methyl‐2‐butanol (MBO), the acid catalysed rearrangements in 2N‐0,1N sulfuric acid. ‐ Thermal rearrangements. The N‐(1′,1′‐dimethylallyl)anilines rearrange in MBO at 200‐260° with the exception of the p‐cyano compound 10 in a clean reaction to give the corresponding 2‐(3′‐methyl‐2′‐butenyl)anilines 22–26 (Table 2 and 3). The amount of splitting into the anilines is 10 gives ≃ 40% splitting). The secondary kinetic deuterium isotope effect (SKIDI) of the rearrangement of 5 and its 2′,3′,3′‐d3‐isomer 5 amounts to 0.89±0.09 at 260° (Table 4). This indicates that the partial formation of the new s̀‐bond C(2), C(3′) occurs already in the transition state, as is known from other established [3,3]‐sigmatropic rearrangements. The rearrangement of the N‐(1′‐methylallyl)anilines 12–14 in MBO takes place at 290–310° to give (E)/(Z)‐mixtures of the corresponding 2‐(2′‐Butenyl)anilines ((E)‐ and (Z)‐30,‐31, and ‐32) besides the parent anilines (5–23%). Since a dependence is observed between the (E)/(Z)‐ratio and the bulkiness of the o‐substituent (H: (E)‐30/(Z)‐30=4,9; t‐C4H9: (E)‐32/(Z)‐32=35.5; cf. Table 6), it can be concluded, that the thermal amino‐Claisen rearrangement occurs preferentially via a chair‐like transition state (Scheme 22). Methyl substitution at C(3′) in the allyl chain hinders the thermal amino‐Claisen‐rearrangement almost completely, since heating of (E)‐and (Z)‐16, in MBO at 335° leads to the formation of the expected 2‐(1′‐methyl‐allyl) aniline (33) to an extent of only 12 and 5%, respectively (Scheme 9). The main reaction (≃60%) represents the splitting into aniline. This is the only observable reaction in the case of 17. The inversion of the allyl chain in 16 ‐ (E)‐ and (Z)‐30 cannot be detected ‐ indicated that 33 is also formed in a [3, 3]‐sigmatropic process. This is also true for the thermal transformation of N‐allyl‐(1) and N‐allyl‐N‐methylaniline (15) into 2 and 34, respectively, since the thermal rearrangement of 2′, 3′, 3′‐d3‐1 yields 1′, 1′, 2′‐d3‐2 exclusively (Table 8). These reaction are accompanied to an appreciable extent by homolysis of the N, C (1′) bond: compound 1 yields up to 40% of aniline and 15 even 60% of N‐methylaniline ((Scheme 10 and 11). The activation parameters were determined for the thermal rearrangements of 1, 5, 12 and 15 in MBO (Table 22). All rearrangements show little solvent dependence (Table 5, 7 and 9). The observed ΔH≠ values are in the range of 34‐40 kcal/mol and the ΔS≠ values very between ‐13 to ‐19 e.u. These values are only compatible with a cyclic six‐membered transition state of little polarity. ‐ Acid catalysed rearrangements. ‐ The rearrangement of the N‐(1′, 1′‐dimethylallyl) anilines 5‐10 occurs in 2N sulfuric acid already at 50‐70° to give te 2‐(3′‐methyl‐2′‐butenyl)anilines 22‐27 accompanied by their hydrated forms, i.e. the 2‐(3′‐hydroxy‐3′‐methylbutyl) anilines 35‐40 (Tables 10 and 11). The latter are no more present when the rearrangement is conducted in 0.1 N sulfuric acid, whilst the rate of rearrangement is practically the same as in 2 N sulfuric acid (Table 12). The acid catalysed rearrangements take place with almost no splitting. The SKIDI of the rearrangement of 5 and 2′, 3′, 3′‐d3‐5 is 0.84±0.08 (2 N H2SO4, 67, 5°, cf. Table 13) and thus in accordance with a [3,3]‐sigmatropic process which occurs in the corresponding anilinium ions. Consequently, the rearrangement of a 1:1 mixture of 2′, 3′, 3′‐d3‐5 and 3, 5‐d2‐5 in 2 N sulfuric acid at 67, 5° occurs without the formation of cross‐products (Scheme 13). In the acid catalysed rearrangement of the N‐1′‐methylallyl) anilines 12‐14 at 105‐125° in 2 N sulfuric acid the corresponding (E)‐ and (Z)‐anilines are the only products formed (Table 14 and 15). Again no splitting is observed. Furthermore, a dependence of the observed (E)/(Z) ratio and the bulkiness of the o‐substituent (H: (E)/(Z)‐30 = 6.5; t‐C4H9: (E)‐32/(Z)‐32 = 90; cf. Table 15) indicates that also in the ammonium‐Claisen rearrangement a chair‐like transition state is preferentially adopted. In contrast to the thermal rearrangement the acid catalysed transformation in 2 N‐O, 1 N sulfuric acid (150‐170°) of (E)‐ and (Z)‐16 as well as of 1 and 15, occurs very cleanly to yield the corresponding 2‐allylated anilines 33, 2 and 34 (Scheme 15 and 18). The amounts of the anilines formed by splitting are E)‐ and )Z)‐16 the indoline 45 is formed (Scheme 15 and 18). All transformations occur with inversion of the allyl chain. This holds also for the rearrangement of 1, since 3′, 3′‐d2‐1 gives only 1′, 1′‐d2‐2 (Scheme 17). The activation parameters were determined for the acid catalysed rearrangement of 1, 5, 12 and 15 in 2 N sulfuric acid (Table 22). The ΔH≠ values of 27‐30 kcal‐mol and the ΔS≠ values of +9 to ‐12 e.u. are in agreement with a [3, 3]‐sigmatropic process in the corresponding anilinium ions. The acceleration factors (kH+/kΔ) calculated from the activation parameters of the acid catalysed and thermal rearrangements of the anilines are in the order of 105 ‐ 107. They demonstrate that the essential driving force of the ammonium‐Claisen rearrangement is the ‘delocalisation of the positive charge’ in the transition state of these rearrangements (cf. Table 23). Solvation effects in the anilinium ions, which can be influenced sterically, also seem to play a role. This is impressively demonstrated by N‐(1′, 1′‐dimethylallyl)‐2, 6‐dimethylaniline (11): its rearrangement into 4‐(1′, 1′‐dimethylallyl)‐2, 6‐dimethylaniline (43) cannot be achieved thermally, but occurs readily at 30° in 2 N sulfuric acid.From a preparative standpoint the acid catalysed rearrangement in 2 N‐0, 1 N sulfuric acid of N‐allylanilines into 2‐allylanilines, or if the o‐positions are occupied into 4‐allylanilines, is without doubt a useful synthetic method (cf. also [17]).