JPH0376309B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to a method for producing a ring expansion product with a nitrogen atom from a heterocyclic cationic compound. Ring expansion products can be produced in which one atom has been introduced. [Prior Art] Conventionally, as ring expansion reaction reagents using nitrogen atoms of heterocyclic cationic compounds, azide salts, N-unsubstituted sulfyl imines, hydroxyamine-O-sulfonic acids, N-unsubstituted sulfenamides (patent application 1983) have been used.
-053702) are known. However, when using azide salts and sulfoylimines, heating or light irradiation is often required to generate nitrene after addition to the cation, and this cannot be applied if the products are unstable to heat or light. It had drawbacks. Further, in the reaction of hydroxylamine-O-sulfonic acid with an acridinium salt, it is necessary to use strongly basic liquid ammonium as a solvent, and these are the only known reaction examples. on the other hand,
In the method using N-unsubstituted sulfenamide, the reaction proceeds under mild conditions (not requiring heat, light, base, etc.), but the types of applicable heterocyclic cation compounds are limited. [Problems to be Solved by the Invention] Conventionally known ring expansion reaction reagents have the above-mentioned drawbacks. An object of the present invention is to provide a method for producing a ring-extended product with a nitrogen atom, which can be reacted at room temperature, simply, rapidly, and in good yield. [Means for Solving the Problems] The present invention provides a general formula, (In the formula, X and Y represent a hetero atom, R represents hydrogen or a reaction-inert substituent, and Z ^- represents a counter anion. The number of ring members in the cation moiety is 5, and X and R may be bonded by a covalent bond.) A general formula characterized by reacting a multi-ring cationic compound represented by (In the formula, X and Y represent a heteroatom, R represents hydrogen or a reaction-inactive substituent, and the number of ring members is 6
and X and R may be connected by a covalent bond. ), and a general formula, A general formula characterized by reacting a triiodide represented by and ammonia, (In the formula, X and Y represent a heteroatom, R represents hydrogen or a reaction-inactive substituent, and the number of ring members is 6
and X and R may be connected by a covalent bond. ) is a method for producing a ring expansion product with a nitrogen atom represented by According to the method of the present invention, the reaction proceeds rapidly under mild conditions (no heat or light required), and since the reaction reagents are inorganic iodine and ammonia, the product can be separated and purified (extracted, (column, recrystallization, etc.) can be carried out effectively, and the desired ring expansion product can be obtained in good yield. Furthermore, the chlorine ring compounds produced by the method of the present invention contain a plurality of heteroatoms and are often difficult to synthesize by other methods. Furthermore, six-membered ring compounds containing sulfur atoms and nitrogen atoms are of interest in terms of structure, physical properties, pharmacological effects, etc., and are considered to be useful compounds in organic synthesis. R in the heterocyclic cationic compound represented by the general formula and used in the present invention is hydrogen or an inert substituent, and examples of the inert substituent include a dimethylamino group, a diisopropylamino group, a piperidino group, and a morpholino group. group, methylphenylamino group, methylthio group, ethylthio group, phenyl group, p-chlorophenyl group, p-enisyl group, and the like. Furthermore, examples of the heteroatoms X and Y include oxygen atoms, sulfur atoms, nitrogen atoms, and the like. Examples of the counter anion Z ⁻ in the general formula include perchlorate anion, tetrafluoroborate anion, chlorine anion, and iodine anion. Specific examples of the heterocyclic cationic compound represented by the general formula include (1) 5-diethylamino-3-phenyl-1,4,2-dithiazolium perchlorate, (2) 5-methylthio-3-phenyl-1 ,4,
2-dithiazolium perchlorate, (3) 3,5-diphenyl-1,4,2-dithiazolium perchlorate, (4) 5-diethylamino-3-(1-naphthyl)
-1,4,2-dithiazolium perchlorate, (5)2
-dimethylamino-4-phenyl-1,3-dithiolium tetrafluoroborate, (6)2,4-diphenyl-1,3-dithiolium perchlorate, (7)4,
5-diphenyl-1,3-dithiolium perchlorate, (8) 2-dimethylamino-4,5-diphenyl-1,3-dithiolium perchlorate, (9) 2,4,
5-triphenyl-1,3-dithiolium perchlorate, (10)2-piperidino-5-phenyl-1,3
-Oxathiolium perchlorate, (11)2,5-
Diphenyl-1,3-oxathiolium tetrafluoroborate, (12) 2-methylthio-1,3-dithioranylium iodide, (13) 2,3,5,6
-tetrahydrothiazolo[2,3-b]thiazolium chloride and the like. Examples of the triiodide represented by the general formula include those in which the counter anion of the above-mentioned heterocyclic cation compound is replaced with I ₃ ^- . The structural formulas of each of the compounds (1) to (13) above are as follows.

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〔Example〕

Next, the present invention will be explained in more detail based on examples. Example 1 5-diethylamino-3-phenyl-1,4,
2-dithiazolium perchlorate 350mg (1mmol)
and iodine 254 mg (1 mmol) were dissolved in acetonitrile (6 ml), and 28% ammonia water was added under stirring at room temperature.
Add 0.6ml. After about 10 minutes, the reaction solution was poured into water and extracted with dichloromethane. After evaporating the solvent, the residue was treated with silica gel column chromatography and recrystallized from dichloromethane-hexane to give pale yellow crystals of 3-diethylamino-6-phenyl-1,4,2,5- with a melting point of 71.0-71.5°C. 144 mg (yield 54%) of dithiadiazine was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ = 1.21 (6H, t,
J = 7.5Hz), 3.53 (4H, q, J = 7.5Hz), 7.4-7.6 (3H, m), 7.9-8.1 (2H, m) MS (m/z) 265 (M ⁺ ), 232 (M ⁺ −SH), 121
(phCS ⁺ ) Elemental analysis value (%) Measured value C 54.13 H 5.67 N 15.83 S 24.07 Calculated value C 54.31 H 5.70 N 15.83 S 24.16 Example 2 2,4-diphenyl-1,3-dithiolium triiodide 636 mg (1 mmol) ) to acetonitrile 6
ml of 28% ammonia water under stirring at room temperature.
Add. Hereinafter, when processed in the same manner as in Example 1,
Yellow crystals 100 mg (33%) of 3,5-diphenyl-1,4,2-dithiazine and 3,6-diphenyl-1,
70 mg (23%) of an isomer mixture of 4,2-dithiazine was obtained. These are standard specimens [Tetrahedron Lett., 24, 37
29 (1983)], the structure was confirmed. Example 3 2-dimethylamino-4,5-diphenyl-
1,3-dithiolium perchlorate 398mg (1m
254 mg (1 mmol) of iodine prepared in advance
and 1 ml of 28% aqueous ammonia in acetonitrile (10 ml), and stirred at room temperature for 10 minutes. Thereafter, the same procedure as in Example 1 was carried out to obtain 230 mg (74%) of yellow crystals of 3-dimethylamino-5,6-diphenyl-1,4,2-dithiazine. Melting point 164.0−
164.5℃ (acetonitrile-ether) ¹ H-NMR (CDCl ₃ , TMS) δ=3.18 (6H,
S), 7.1−7.5 (10H, m) MS (m/z) 312 (M ⁺ ), 242 ((PhCS) ₂ ⁺ ), 178
(PhCCPh ⁺ ), 121 (PhCS ⁺ ) Elemental analysis (%) Measured value C 65.36 H 5.16 N 8.91 S 20.39 Calculated value C 65.35 H 5.16 N 8.97 S 20.52 Example 4 2,5-diphenyl 1,3-oxathiolium Dissolve 310 mg (0.5 mmol) of triiodide in 3 ml of acetonitrile, and add 28% aqueous ammonia (0.3 ml) while stirring at room temperature. Hereinafter, when treated in the same manner as in Example 1, orange crystals 3,6-diphenyl-1,
39 mg (31%) of 4,2-oxathiazine was obtained. Melting point 105.0-105.5℃ (acetonitrile). ^1H -NMR ( _CDCl3 , TMS) δ=6.20 (1H,
S), 7.3-7.6 (6H, m), 7.6-7.9 (2H, m), 8.0
−8.2 (2H, m) MS (m/z) 253 (M ⁺ ), 150

[Formula] 105 (PhCO ⁺ ) Elemental analysis value (%) Measured value C 71.14 H 4.35 N 5.51 S 12.64 Calculated value C 71.12 H 4.38 N 5.53 S 12.66 Example 5 2-Methylthio-1,3-dithioranylium iodide 278 mg (1 mmol) and iodine 254 mg (1 m
mol) in acetonitrile (6 ml) and add 0.6 ml of 28% aqueous ammonia while stirring at room temperature. below,
When treated in the same manner as in Example 1, a colorless and transparent oily substance 3-methylthio-4,5-dihydro-1,4,
56 mg (34%) of 2-dithiazine was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ = 2.38 (3H,
S), 3.1−3.5 (4H, m) ¹³ C-NMR (CDCl ₃ , TMS) δ = 13.94, 26.91,
28.64, 149.29 MS (m/z) 165 (M ⁺ ), 92

〔Effect of the invention〕

According to the present invention, by treating a heterocyclic cation compound with an iodine-ammonia system,
A ring expansion product in which one nitrogen atom is introduced into the ring can be produced rapidly and in good yield. Furthermore, compared to conventional methods, the reaction can proceed under mild conditions (no heat or light required), making it a manufacturing method with a wide range of applications. In addition, the reagents used are very inexpensive iodine and ammonia water, and post-treatment is easy. Many of the six-membered heterocyclic compounds produced in this reaction have antiaromatic properties (8π electron system), and their physical properties and structures are of interest. In particular, elemental sulfur, nitrile sulfide, etc. are generated by light irradiation or heating, which can serve as a reactive sulfur source or a precursor of nitrile sulfide, which is a useful reaction intermediate in organic synthesis chemistry. Conceivable. From the standpoint of molecular design, this reaction also allows one nitrogen atom to be
This method provides a novel method for introducing into a single ring, and many of the heterocyclic cationic compounds used in this reaction are used as reaction intermediates in the agricultural and pharmaceutical fields, making it possible to develop compounds with new pharmacological effects. It is thought that it has the potential to generate.

Claims (1)

[Claims] 1 General formula, (In the formula, X and Y represent a hetero atom, R represents hydrogen or a reaction-inert substituent, and Z ^- represents a counter anion. The number of ring members in the cation moiety is 5, and X and R may be bonded by a covalent bond.) A general formula characterized by reacting a heterocyclic cationic compound represented by (In the formula, X and Y represent a hetero atom, and R represents hydrogen or a reaction-inactive substituent. Also, the number of ring members is 6
and X and R may be connected by a covalent bond. ) A method for producing a ring expansion product with a nitrogen atom represented by 2 general formula, (In the formula, X and Y represent a hetero atom, and R represents hydrogen or a reaction-inactive substituent. The number of ring members in the cation moiety is 5, and X and R may be connected by a covalent bond. A general formula characterized by reacting triiodide and ammonia represented by (In the formula, X and Y represent a hetero atom, and R represents hydrogen or a reaction-inactive substituent. Also, the number of ring members is 6
and X and R may be connected by a covalent bond. ) A method for producing a ring expansion product with a nitrogen atom represented by