Cyclization of 1-(2-Alkynylphenyl)-3,3-dialkyltriazenes:  A Convenient, High-Yield Synthesis of Substituted Cinnolines and Isoindazoles

Abstract

A new route to isoindazoles and cinnolines through the cyclization of (2-alkynylphenyl)triazenes under neutral conditions is presented. The products that result from heating the starting triazenes depend on both the type of alkyne ortho to the triazene functionality and the temperature used. Butadiyne moieties ortho to dialkyltriazenes yield bis-isoindazole dimers when heated to 150 degrees C in MeI. A requirement for cyclization in MeI is that the (2-alkynylphenyl)triazene must contain a suitably electron-withdrawing substituent on the phenyl ring to deactivate the triazene toward methylation-induced decomposition to an iodoarene. Ethynyl moieties ortho to dialkyltriazenes yield both isoindazole dimers as well as 3-formylisoindazoles when subjected to the same conditions. Replacing MeI with 1,2-dichlorobenzene as solvent allows for the general cyclization of (2-ethynylphenyl)dialkyltriazenes. Heating to 170 degrees C results in a mixture of isoindazole and cinnoline products, whereas the cinnolines are produced exclusively in high yield at 200 degrees C. Alternatively, the isoindazoles can be obtained in good to excellent yield by stirring a 1,2-dichloroethane solution of the starting triazene with CuCl overnight at 50 degrees C.

Superstructure‐Dependent Optical and Electrical Properties of an Unusual Face‐to‐Face, π‐Stacked, One‐Dimensional Assembly of Dehydrobenzo[12]annulene in the Crystalline State

“…Synthesis and crystallization of the [12]DBAs: [12]DBA 2 was synthesized with a 71 % yield by the hydrolysis of the corresponding methyl ester 3, which is derived from the iod-ization of the diethyltriazene derivative 4 [23] with a 69 % yield and desilylation followed by modified Castro-Stephens cyclization [24] of the resultant iodoethynylbenzene derivative 6 with a 39 % yield in two steps, as shown in Scheme 1.…”

“…Other details of the apparatus are described elsewhere. [30] Methyl 4-iodo-3-trimethylsilylethynylbenzenoate (5): Diethyltriazene 4 (100 mg, 0.302 mmol), which was synthesized according to the report by Haley et al, [23] was dissolved in methyl iodide (2 mL) in an autoclave under a nitrogen atmosphere. The reaction vessel was placed in an oil bath at 120 8C for 17 h. After cooling to room temperature, the solvent was removed under reduced pressure.…”

Coarctate cyclization reactions: a primer

“…Cyclizations at 170 1C gave a prototypical kinetic/thermodynamic product distribution of isoindazole and cinnoline. 10 This also explained why the cinnoline formed exclusively in high yield when the cyclization was done at higher temperatures. An essential piece of evidence for our proposed pathways, however, was the demonstration of reversibility of the coarctate process.…”

“…Simply heating the starting triazenes 9 in ODCB to 200 1C in a pressure tube gave cinnolines 12 in excellent yield. 10 As mentioned earlier, our first inclination was that cinnoline production occurred by means of a Bergman-type cyclization to give a 1,4-diradical species; however, experiments performed in the presence of radical donors allowed Dave to discount this mechanistic pathway. Subsequent results with benzhydrol containing one or two deuterium atoms suggested that C4 in the intermediate in cinnoline formation had a propensity for proton/deuterium abstraction from the strong but rather acidic O-H(D) bond.…”

Methods for the synthesis of cinnolines (review)

“…Another example of the cyclization of ortho-ethynyl-substituted triazines by heating the compounds in ortho-dichlorobenzene was described in Kimball's papers [85][86][87][88][89]. Initially, on heating to 170°C a mixture of products was obtained -the isoindazole 22 and cinnoline 23 in a ratio of 1:1 (Scheme 26).…”