Pericyclic Domino reactions with 3,6-Bis(trifluoromethyl)-1,2,4,5-tetrazine: A convenient entry into azo cage compounds

Abstract

3,6‐Bis(trifluoromethyl)‐1,2,4,5‐tetrazine (1) characterized by a highly reactive, electron deficient diazdiene system reacted with several cyclic and acyclic bis‐dienophiles to yield the cage compounds 11, 19a, b, 31a, b and 41 in a pericyclic homo‐domino reaction in good yields. The first step of the domino reactions is an inverse electron demand inter‐molecular Diels–Alder addition followed by elimination of nitrogen to give 4,5‐dihydropyridazines which then undergo a terminal ring closure to yield the cage compounds. The solvent employed and the reaction temperature is of crucial importance. Whereas in nitromethane and at elevated temperatures the main products are the cage compounds, at lower temperature and in dichloromethane as solvent the initially formed 4,5‐dihydropyridazines are frequently converted to 1,4‐dihydropyridazines by a 1,3‐H‐shift. Treatment of the tetrazine 1 with cyclooctatriene 23 did not lead to a cage compound in any case; instead via valence tautomeric species octa‐1,3,5,7‐tetraene 23a and bicyclo[4.2.0]octa‐2,4‐diene 23b the twofold pyridazine‐substituted butadienes 24 and 26 together with the tricyclic cyclobuta[f]phthalazine 25 were formed.

Study of the Formation and Thermal Decomposition of an Azo‐Bridged Tricyclic Ring System

“…Analysis of the chromatograms unambiguously proved the presence of the appropriate secondary amine 13a,b and a C 3 fragment, although not in the form of propyne but propanal (14). Dimethyl 4-methylpyridazine-3,6-dicarboxylate (9) was also identified in the pyrolysate along with varying minor amounts (up to 6 %) of other products, such as dimethyl pyridazine-3,6-dicarboxylate (11), and the N-methyl (15a,b) and N-propenyl (16a,b) derivatives [19] of the appropriate amine (Scheme 3). The formation of propanal was rationalised by hydrolysis of the enamines 16a,b under the analysis conditions.…”

“…The structure of the product, which was confirmed by X-ray analysis, suggests that the reaction proceeds via a domino "inverse electron-demand" Diels-Alder reaction. [11] The first reaction takes place at the sterically less hindered disubstituted double bond [12] as before, giving 4, and this then undergoes another intramolecular "inverse electrondemand" Diels-Alder reaction, or alternatively reacts with another molecule of 2, as previously reported for 1-amino-4-hetaryl-2-methyl-1,3-butadienes. [8]…”

(–)-(M,7S)-Colchicine and (–)-(M,7S)-10-Ethylthiocolchicide/Alkyne Cycloaddition Reactions: Synthesis of Novel Colchicine Derivatives by Consecutive [4+2] and [3+2] Cycloadditions

“…for 40 h. After cooling to room temp., the solvent was evaporated in vacuo. TLC control exhibited that a complex mixture of prod-[7S-(7Ͱ,8Ͱ,17Ͱ)]-N- (5,6,7,8,9,11,12,13,14,15,16,17,20,21,22, ucts was formed with two main products, which could be separated 23,24,2,17[1Ј,2Ј] -5,6,7,8,9,13-hexa-cm Ϫ1 (ν NϪH ), 1650 cm Ϫ1 (ν CϭO ). Ϫ UV (MeOH): λ max (lg ε) ϭ 337 hydro -1,2,3-trimethoxy-9-oxo-8,13-ethenobenzo[6Ј,7Ј] [1Ј,2Ј:4,5]cyclohepta [1,12,14,CHCl 3 3.928 (s, 3 H, (C-3), 155.57 (C-16b) [7S-(7Ͱ,8β,17β)]-N- (5,6,7,8,9,11,12,13,14,15,16,17,20,21,22, C-7), 39.26 (CH 2 , C-6), 49.15 (CH, C-5), 52.58 (CH 3 ,COOCH 3 ),23,24,2,17[1Ј,2Ј] …”

“…ZORTEP plot of the structure of cycloadduct 19 in the crystal [4] ; thermal ellipsoids at the 40% probability level, the numbering of the atoms differs from that given in the experimental section for financial support. We also wish to thank Mrs. S. Thoret for the 9.5:0.5); fraction 1 contained 1, fraction 2 contained 108 mg ( [8] .…”

“…The lattice constants of the hexagonal unit cell, space group P3 2 (Z ϭ 6, d calcd. ϭ 1.275 mg mm Ϫ3 ) were refined with the chromatography (silica gel, column 20 ϫ 3 cm, CH 2 Dimethyl 8, : 8,2]cyclooct [1] 3.75 (s,3 H,140.72 (CH,140.89 (CH,, 141.61 (C-2) …”