Synthesis of 2-amino-4H-3,1-benzoxazines and 2-amino-4H-3,1-benzothiazines by the rearrangement of o-cyclopropylphenylureas and o-cyclopropylphenylthioureas

Abstract

Syntheses are reported for 2-cyclopropylphenylureas and 2-cyclopropylphenylthioureas and the behavior of these compounds was studied under conditions for the acid-catalyzed opening of the cyclopropyl ring. Upon the action of concentrated sulfuric acid or trifluoroacetic acid, these ureas and thioureas can undergo rearrangement to the corresponding 3,1-benzoxazines and 3,1-benzothiazines.Functionally-substituted cyclopropanes, which have now become readily available, are finding increasing use as starting compounds in the synthesis of various organic compounds produced by the transformation of the three-membered ring upon the action of specific reagents. These transformations may yield either saturated or unsaturated acyclic products of opening of the cyclopropyl ring [1-4] or carbo-and heterocycles [5][6][7][8][9][10][11]. An especially large number of studies have been devoted to donor-acceptor functionally-substituted cyclopropanes [11]. The reactions in this case proceed predominantly with the participation or effect of the substituents directly bound to the three-carbon ring. There has been considerably less work on the transformations of cyclopropane compounds, in which the substituents, not directly bound to the cyclopropane ring, participate in the reaction. Nevertheless, examples of such transformations [9,[12][13][14] show that the synthetic scope of functionally-substituted cyclopropanes may be considerably expanded. Here, definite promise is found in intramolecular acid-catalyzed ortho-substituted arylcyclopropanes due to the unique ortho-orienting effect of the cyclopropane substituent in electrophilic nitration reactions [15][16][17]. These reagents are now readily available.In a search for new examples of the intramolecular rearrangement of ortho-functionally-substituted arylcyclopropanes, we synthesized 2-cyclopropylphenylureas and 2-cyclopropylphenylthioureas and studied their transformations in trifluoroacetic and concentrated sulfuric acids. We assumed that the acid-catalyzed opening of the cyclopropane ring in suitable cyclopropylureas and cyclopropylthioureas would initiate reaction of the resultant benzylic carbenium ion with the internal nucleophile (urea or thiourea fragment) to form 2-amino-3,1-benzoxazines and 3,1-benzothiazines or isomeric compounds. _______ * Deceased. __________________________________________________________________________________________

Tandem addition-cyclization reaction catalyzed by ytterbium chloride: An efficient one-step synthesis of 2-amino-4H-3,1-benzothiazine

“…It can be confirmed that solvent conditions play an important role in affecting the tautomeric equilibrium. This result is slightly different from that obtained by Shabarov and coworkers [22]. Interestingly, another type of cyclization product 5 (Scheme 1), which can be formed through an intramolecular N-nucleophilic attack rather than S-nucleophilic attack, was not observed.…”