A New Synthetic Route to 1-Halogeno-1-cyclopropanecarboxylates

Abstract

Substituted bicyclic 1-halogeno-1-cyclopropanecarboxylates have been prepared by elimination of molecular nitrogen from 4-halogeno-7-aryl-1-methyl-2,3,7-triazabicylo[3.3.0]oct-2-en-4-carboxylates, which were obtained by the reaction of 7-aryl-1-methyl-2,3,7-triazabicyclo[3.3.0]oct-3-encarboxylates with halogens (Cl 2 , Br 2 ).The most general methods of synthesis of 1-halogeno-1-cyclopropanecarboxylates are lithiation of gem-dihalogencyclopropanes by RLi with formation of 1-halogeno-1-lithiocyclopropanes and their subsequent interaction with carbon dioxide, 1 the reactions of diazocompounds with esters of substituted α-halogenoacrylic acids, 2 and also the reactions of esters of diazohalogenoacetic acids with unsaturated compounds. 3 In this present work 1-halogeno-1-cyclopropanecarboxylates have been prepared by thermal removal of nitrogen from pyrazolines, known to be a rather convenient method of synthesis of cyclopropanes. 4On reaction of 7-aryl-1-methyl-6,8-dioxo-2,3,7-triazabicyclo[3.3.0]oct-3-en-4-carboxylates 1a-g 5 with chlorine in chloroform at 0°C, esters of 7-aryl-1-methyl-4-chloro-6,8-dioxo-2,3,7-triazabicyclo[3.3.0]oct-2-en-4-carboxylates 2a-g were formed as a mixture of endo-and exo-isomers in 69-84% yield (endo/exo-ratio -8:1) (Table).Heating of esters 2a-g in vacuo at 120°C led to the extrusion of nitrogen and the formation of esters of 1-chlorocyclopropanecarboxylic acids 3a-g. It is important to note, that thermolysis of endo-isomers 2a-d resulted only in endo-isomers 3a-d, while on heating for the same time the exo-isomer 2a-d formed a mixture of endo-and exoisomers 3a-d. Reaction of the pyrazolines 1h,j,m 5 with chlorine at 0°C in 1,2-dichloroethane resulted directly in esters of 1-chlorocyclopropanecarboxylic of acids 3n-p with an endo-configuration in yield 88-94% (Table).On reaction of ester 1a with bromine in chloroform at 60°C a bromopyrazoline 2h was obtained with a yield of 36%. In all probability, this had an exo-configuration; thermolysis of this in vacuo at 120°C resulted in the formation an ester 3h as a mixture of exo-and endo-isomers in the ratio 3.1:1 Reaction of pyrazolines 1h-l with bromine in glacial acetic acid at 70°C resulted directly in 1-bromocyclopropanecarboxylates 3i-m in 63-81% yield as a mixture of endo-and exo-isomers. Table Compounds 2 and 3 preparedTypical experimental procedures were as follows: Ethyl 7-p-tolyl-1-methyl-4-chloro-6,8-dioxo-2,3,7-triazabicyclo[3.3.0]oct-2-en-4-endo-carboxylate (2a). Into a solution (0.35 g, 1.1 mmol) of ester 1a in of dry chloroform (30 ml) at 0°C was passed a stream of dry chlorine till saturation (excess, during 1 min). Chloroform was evaporated in vacuo at room temperature, and the residue (mixture endo/exo as 8:1) was crystallized from methanol to give ester endo2a; yield 0.27 g (69%), mp 98-99°C (dec.). 1 H NMR(300 MHz) δ: endo-2a -1.42 (t, 3H, J = 7 Hz), 2.01 (s 3H), 2.40 (s, 3H), 3.74 (s, 1H), 4.42 (q, 2H, J = 7 Hz), 7.15 (d, 2H, J = 8 Hz), 7.28 (d, 2H, J = 8 Hz); signals of exo-2a -3.43 (s, 1H), 3.88 (s, 3H), other signals...

Highly Stereoselective Halocyclopropanation of α,β‐Unsaturated Amides

“…[11c,d,12c-d,13,14b-d, 15,16,17] In the case of bromocyclopropanation, to the best of our knowledge only one stereoselective synthesis of bromocyclopropanes has been reported via the bromination of cyclopropylindium reagents prepared from the allylindation of cyclopropenes which are not readily available. [18] The most employed method for the synthesis of bromocyclopropanes is based on the debromination of dibromocyclopropanes by using several reagents.…”

“…[10] The chlorocyclopropane motif can be mainly accessed through the addition of carbenoids (SimmonsSmith-like process) [11] or carbene [12] species to double bonds; from a,a-dichloroalkyl anions (conjugated nucleophilic addition followed by a ring closing reaction), [13] from gem-dichlorocyclopropanes, [14] and by utilizing other starting materials such as 2,2-dichlorobutanols (Favorskii rearrangement), [15] carboalkoxychlorodiazirines, [16] or pyrazolines. [17] However, the majority of these methods present some drawbacks such as: a) the use of explosive, flammable or harmful reagents [12b-c,16] or those which are not readily available;…”

“…[13b, 16,17] b) some methods proceed with low stereoselectivity, [11c-d,12c,13d,14b-c,16] or in poor yields; [11b-d,13a-b,d] and finally d) other methods have shown poor generality.…”

Reactions of Substituted Ethyl 1,2,3,4,4′,5′-Hexahydrospiro-[naphthalene-2,5′-pyrazole]-3′-carboxylates with Halogens

“…Thermolysis of the latter is accompanied by loss of nitrogen molecule to afford substituted 1-halocyclopropanecarboxylates [1][2][3][4][5][6]. In the present work we examined reactions of ethyl 4'-aryl-1-oxo-1,2,3,4,4',5'-hexahydro-1'H-spiro[naphthalene-2,5'-pyrazole]-3'-carboxylates Ia-Ic with chlorine and N-bromosuccinimide and isolated ethyl 4'-aryl-3'-chloro-1-oxo-1,2,3,4,4',5'-hexahydro-3'Hspiro[naphthalene-2,5'-pyrazole]-3'-carboxylates IIaIIc in 44-72% yield and their 3'-bromo-substituted analogs IIIa-IIIc in 45-61% yield (Scheme 1).…”