碘化1-甲基-2-异丙基(或丙基)-3-苯磺酰基咪唑啉的合成及基团转移反应

doi:10.7503/cjcu20141144

摘要/Abstract

摘要：

合成了新的四氢叶酸辅酶(THF)模型化合物碘化1-甲基-2-异丙基-3-苯磺酰基咪唑啉(5a)和碘化1-甲基-2-丙基-3-苯磺酰基咪唑啉(5b), 研究了其反应性能. 结果表明, 化合物5与双官能团亲核体邻苯二胺或邻氨基苯酚反应, 完全转移了4个碳的异丁基和正丁基单元, 基于此探索了合成2-取代苯并咪唑及2-取代苯并唑的新方法; 化合物5a与单官能团亲核体胺类反应部分转移了4个碳的异丁基单元, 生成不同基团取代的N,N,N'-三取代乙二胺盐; 化合物5a在NaBH₄作用下可发生还原反应, 在NaOH水溶液中可发生水解反应, 也可与碳负离子基团(硝基甲基负离子或二腈基甲基负离子)发生亲核加成反应, 生成了3类不同基团取代的N,N,N'-三取代乙二胺衍生物, 探索了此类化合物的简易合成方法. 这些反应模拟了四氢叶酸辅酶在生物体内转移一碳单元的功能, 并将其扩展到4个碳原子单元, 获得了可应用于有机合成的新方法和新试剂.

关键词: 四氢叶酸, 咪唑啉盐, 转移反应, 模型, 加成反应

Abstract:

In the course of developing synthetic methods based upon mechanisms of biochemical processes, 1-methyl-2-isopropyl-3-benzenesulfonyl imidazolidinium iodide(5a) and 1-methyl-2-propyl-3-benzenesulfonyl imidazolidinium iodide(5b) were prepared as the tetrahydrofolate model compounds at the oxidation level of formate, which reacting with bifunctional nucleophiles o-phenylenediamine and 2-aminophenol. In the synthe-tic process, four carbon fragments were transferred completely and we found a way directly to benzimidazoles, benzoxazoles. The reaction of the model compound 5a with monofunctional nucleophiles(butylamine, aniline, benzylamine, p-methoxyaniline) afforded the products transferred part of four carbon fragments, containing three different groups of N,N,N'-trisubstituted ethylenediamine salt. Sodium borohydride reduction of 5a afforded compound 9. Treatment of compound 5a with NaOH caused hydrolysis and the corresponding carbonyl compound 10 was formed. The nucleophilic addition reaction of compound 5a with some carbanion(nitrome-thane carbanion and malononitrile carbanion) gave compounds 12 and 13, respectively. Compounds 9, 10, and 12 or 13 are three kinds of containing different groups of N,N,N'-trisubstituted ethylenediamine.

Key words: Tetrahydrofolate, Imidazolinium salt, Transfer reaction, Model, Addition action

中图分类号:

O621.3

TrendMD:

温雪山, 霍明章, 陈建新. 碘化1-甲基-2-异丙基(或丙基)-3-苯磺酰基咪唑啉的合成及基团转移反应. 高等学校化学学报, 2015, 36(5): 893.

WEN Xueshan, HUO Mingzhang, CHEN Jianxin. Synthesis and Group Transfer Reaction of 1-Methyl-2-isopropyl(or propyl)-3-benzenesulfonyl Imidazolidinium Iodide^†. Chem. J. Chinese Universities, 2015, 36(5): 893.

图/表 9

Fig.1 Structure of THF(1) and three kinds of oxidation levels of THF(2—4)

Fig.2 Structures of THF model compounds 5a and 5b

Table 1 Appearance, yields, IR, melting points and elemental analysis results of compounds 5a, 5b, 8a—8d, 9, 10, 12 and 13

Compd.	Appearance	Yield(%)	m.p./℃	IR(KBr), $ν ˙$ /cm^-1	Elemental analysis(%, calcd.)
Compd.	Appearance	Yield(%)	m.p./℃	IR(KBr), $ν ˙$ /cm^-1	C	H	N
5a	Colourless crystals	89.0	134.0—135.0	1679, 1626, 1452, 1190	39.59(39.60)	4.82(4.86)	7.25(7.11)
5b	Yellowish crystals	87.0	126.0—127.5	1680, 1624, 1452, 1190	39.32(39.60)	4.61(4.86)	6.88(7.11)
8a	Yellowish crystals	76.0	124.0—126.0	3488, 1605, 1312, 1237, 1123	43.51(43.68)	6.23(6.47)	8.82(8.99)
8b	Colourless crystals	91.4	120.0—121.0	3486, 1612, 1322, 1223, 1135	47.83(47.91)	5.42(5.63)	8.21(8.38)
8c	Colourless crystals	55.3	119.0—120.0	3487, 1601, 1323, 1186, 1134	46.90(46.82)	5.25(5.38)	8.45(8.62)
8d	Colourless crystals	49.2	103.0—105.0	3485, 1613, 1512, 1223, 1135	46.55(46.43)	5.61(5.45)	8.28(8.12)
9	Colourless liquids	76.4		3486, 1552, 1456, 1135	57.83(57.75)	8.32(8.20)	10.42(10.36)
10	Colourless crystals	85.4	98.5—100.0	3469, 1669, 1550, 1435	54.64(54.91)	7.16(7.09)	9.74(9.85)
12	Colourless crystals	88.2	102.0—104.0	3489, 1649, 1450, 1335, 1187	51.35(51.36)	6.44(6.46)	12.70(12.83)
13	Colourless crystals	67.6	106.0—107.0	3481, 2241, 1643, 1513, 1326	58.01(57.78)	6.07(6.06)	16.62(16.85)

Table 1 Appearance, yields, IR, melting points and elemental analysis results of compounds 5a, 5b, 8a—8d, 9, 10, 12 and 13

Compd.	Appearance	Yield(%)	m.p./℃	IR(KBr), $ν ˙$ /cm^-1	Elemental analysis(%, calcd.)
Compd.	Appearance	Yield(%)	m.p./℃	IR(KBr), $ν ˙$ /cm^-1	C	H	N
5a	Colourless crystals	89.0	134.0—135.0	1679, 1626, 1452, 1190	39.59(39.60)	4.82(4.86)	7.25(7.11)
5b	Yellowish crystals	87.0	126.0—127.5	1680, 1624, 1452, 1190	39.32(39.60)	4.61(4.86)	6.88(7.11)
8a	Yellowish crystals	76.0	124.0—126.0	3488, 1605, 1312, 1237, 1123	43.51(43.68)	6.23(6.47)	8.82(8.99)
8b	Colourless crystals	91.4	120.0—121.0	3486, 1612, 1322, 1223, 1135	47.83(47.91)	5.42(5.63)	8.21(8.38)
8c	Colourless crystals	55.3	119.0—120.0	3487, 1601, 1323, 1186, 1134	46.90(46.82)	5.25(5.38)	8.45(8.62)
8d	Colourless crystals	49.2	103.0—105.0	3485, 1613, 1512, 1223, 1135	46.55(46.43)	5.61(5.45)	8.28(8.12)
9	Colourless liquids	76.4		3486, 1552, 1456, 1135	57.83(57.75)	8.32(8.20)	10.42(10.36)
10	Colourless crystals	85.4	98.5—100.0	3469, 1669, 1550, 1435	54.64(54.91)	7.16(7.09)	9.74(9.85)
12	Colourless crystals	88.2	102.0—104.0	3489, 1649, 1450, 1335, 1187	51.35(51.36)	6.44(6.46)	12.70(12.83)
13	Colourless crystals	67.6	106.0—107.0	3481, 2241, 1643, 1513, 1326	58.01(57.78)	6.07(6.06)	16.62(16.85)

Table 2 1H NMR and 13C NMR data of compounds 5a, 5b, 8a—8d, 9, 10, 12 and 13

Compd.	¹H NMR(600 MHz)	¹³C NMR(151 MHz)
5a^a	7.73—8.15(m, 5H), 4.57(t, J=10.2 Hz, 2H), 4.46(t, J=10.2 Hz, 2H), 3.65—3.70(m, 1H), 3.47(s, 3H), 1.28(d, J=7.2 Hz, 6H)	172.0, 136.2, 136.0, 130.7, 128.1, 53.0, 48.4, 37.5, 26.3, 17.7
5b^a	7.70—8.13(m, 5H), 4.29, (s, 4H), 3.40(s, 3H), 3.01(t, J=7.8 Hz, 2H), 1.68—1.77(m, 2H), 1.11(t, J=7.8 Hz, 3H)	169.7, 136.0, 135.0, 130.4, 128.6, 52.1, 47.3, 36.6, 28.7, 20.4, 14.4
8a^b	7.92(brs, 1H), 7.63—7.82(m, 5H), 3.62(brs, 2H), 3.44(brs, 2H), 3.34—3.41(m, 3H), 3.21(brs, 1H), 3.01(brs, 3H), 1.56(m, 2H), 1.24—1.35(m, 8H), 0.91(t, J=7.6 Hz, 3H)	170.5, 140.6, 133.2, 129.9, 126.9, 53.5, 44.6, 40.6, 32.4, 31.4, 27.4, 19.6, 18.6, 14.1
8b^b	7.97(brs, 1H), 7.64—7.84(m, 5H), 7.33—7.42(m, 5H), 4.76—4.21(m, 2H), 3.66(brs, 2H), 3.33(s, 3H), 3.10—3.16(m, 2H), 3.01—3.08(m, 2H), 1.26—1.20(m, 6H)	171.2, 140.5, 137.7, 133.3, 129.9, 129.1, 127.9, 127.0, 126.9, 53.6, 47.3, 40.5, 27.7, 18.5, 17.8
8c^b	7.60—7.81(m, 10H), 4.05(s, 1H), 3.26—3.34(m, 4H), 3.10(s, 3H), 2.97(s, 1H), 1.27(s, 1H), 0.96(d, J=6.8 Hz, 6H)	172.4, 140.6, 138.1, 132.2, 128.3, 128.1, 126.5, 124.1, 123.3, 55.1, 32.1, 30.6, 20.8, 19.6
Compd.	¹H NMR(600 MHz)	¹³C NMR(151 MHz)
8d^b	10.20, 7.99(brss, 1H), 7.66—7.84(m, 5H), 7.06—7.26(m, 4H), 3.80(s, 3H), 3.70(brs, 2H), 3.09—3.35(m, 7H), 1.25(brs, 6H)	171.7, 159.3, 140.5, 133.3, 129.9, 129.6, 128.3, 126.9, 115.1, 56.0, 53.2, 40.5, 30.5, 19.4, 18.6
9^a	7.51—7.89(m, 5H), 5.50(s, 1H), 3.02(t, J=6.0 Hz, 2H), 2.46(t, J=6.0 Hz, 2H), 2.10(s, 3H), 1.95(d, J=7.5 Hz, 2H), 1.68—1.72(m, 1H), 0.83(d, J=6.6 Hz, 6H)	139.5, 132.7, 129.1, 126.9, 65.5, 55.9, 41.7, 40.0, 25.8, 20.6
10^a	7.47—7.87(m, 5H), 6.43, 6.08(ss, 1H), 3.44—3.47(m, 2H), 3.00—3.15(m, 2H), 2.98, 2.85(ss, 3H), 2.72—2.74(m, 1H), 1.10—1.11(m, 6H)	178.7, 175.6, 140.1, 140.0, 132.7, 132.5, 129.2, 129.1, 126.9, 126.8, 49.6, 47.5, 41.4, 41.1, 35.9, 33.8, 30.5, 29.9, 19.7, 19.1
12^a	7.47—7.86(m, 5H), 6.07(br s, 1H), 3.46(t, J=6.0 Hz, 2H), 3.11(t, J=6.0 Hz, 2H), 2.99(s, 3H), 2.84(s, 1H), 2.71—2.75(m, 1H), 1.12(d, J=6.6 Hz, 6H)	178.7, 140.1, 132.5, 129.1, 126.9, 49.6, 47.5, 41.5, 35.9, 30.5, 19.7, 19.1
13^a	7.28—7.85(m, 5H), 5.75(t, J=6.0 Hz, 1H), 3.68—3.79(m, 2H), 3.30(s, 3H), 3.21—3.29(m, 1H), 3.11—3.20(m, 2H), 1.39(d, J=7.2 Hz, 6H)	180.6, 139.3, 133.2, 129.5, 126.9, 117.8, 117.5, 54.7, 51.5, 42.8, 40.9, 32.9, 19.5

Table 2 1H NMR and 13C NMR data of compounds 5a, 5b, 8a—8d, 9, 10, 12 and 13

Compd.	¹H NMR(600 MHz)	¹³C NMR(151 MHz)
5a^a	7.73—8.15(m, 5H), 4.57(t, J=10.2 Hz, 2H), 4.46(t, J=10.2 Hz, 2H), 3.65—3.70(m, 1H), 3.47(s, 3H), 1.28(d, J=7.2 Hz, 6H)	172.0, 136.2, 136.0, 130.7, 128.1, 53.0, 48.4, 37.5, 26.3, 17.7
5b^a	7.70—8.13(m, 5H), 4.29, (s, 4H), 3.40(s, 3H), 3.01(t, J=7.8 Hz, 2H), 1.68—1.77(m, 2H), 1.11(t, J=7.8 Hz, 3H)	169.7, 136.0, 135.0, 130.4, 128.6, 52.1, 47.3, 36.6, 28.7, 20.4, 14.4
8a^b	7.92(brs, 1H), 7.63—7.82(m, 5H), 3.62(brs, 2H), 3.44(brs, 2H), 3.34—3.41(m, 3H), 3.21(brs, 1H), 3.01(brs, 3H), 1.56(m, 2H), 1.24—1.35(m, 8H), 0.91(t, J=7.6 Hz, 3H)	170.5, 140.6, 133.2, 129.9, 126.9, 53.5, 44.6, 40.6, 32.4, 31.4, 27.4, 19.6, 18.6, 14.1
8b^b	7.97(brs, 1H), 7.64—7.84(m, 5H), 7.33—7.42(m, 5H), 4.76—4.21(m, 2H), 3.66(brs, 2H), 3.33(s, 3H), 3.10—3.16(m, 2H), 3.01—3.08(m, 2H), 1.26—1.20(m, 6H)	171.2, 140.5, 137.7, 133.3, 129.9, 129.1, 127.9, 127.0, 126.9, 53.6, 47.3, 40.5, 27.7, 18.5, 17.8
8c^b	7.60—7.81(m, 10H), 4.05(s, 1H), 3.26—3.34(m, 4H), 3.10(s, 3H), 2.97(s, 1H), 1.27(s, 1H), 0.96(d, J=6.8 Hz, 6H)	172.4, 140.6, 138.1, 132.2, 128.3, 128.1, 126.5, 124.1, 123.3, 55.1, 32.1, 30.6, 20.8, 19.6
Compd.	¹H NMR(600 MHz)	¹³C NMR(151 MHz)
8d^b	10.20, 7.99(brss, 1H), 7.66—7.84(m, 5H), 7.06—7.26(m, 4H), 3.80(s, 3H), 3.70(brs, 2H), 3.09—3.35(m, 7H), 1.25(brs, 6H)	171.7, 159.3, 140.5, 133.3, 129.9, 129.6, 128.3, 126.9, 115.1, 56.0, 53.2, 40.5, 30.5, 19.4, 18.6
9^a	7.51—7.89(m, 5H), 5.50(s, 1H), 3.02(t, J=6.0 Hz, 2H), 2.46(t, J=6.0 Hz, 2H), 2.10(s, 3H), 1.95(d, J=7.5 Hz, 2H), 1.68—1.72(m, 1H), 0.83(d, J=6.6 Hz, 6H)	139.5, 132.7, 129.1, 126.9, 65.5, 55.9, 41.7, 40.0, 25.8, 20.6
10^a	7.47—7.87(m, 5H), 6.43, 6.08(ss, 1H), 3.44—3.47(m, 2H), 3.00—3.15(m, 2H), 2.98, 2.85(ss, 3H), 2.72—2.74(m, 1H), 1.10—1.11(m, 6H)	178.7, 175.6, 140.1, 140.0, 132.7, 132.5, 129.2, 129.1, 126.9, 126.8, 49.6, 47.5, 41.4, 41.1, 35.9, 33.8, 30.5, 29.9, 19.7, 19.1
12^a	7.47—7.86(m, 5H), 6.07(br s, 1H), 3.46(t, J=6.0 Hz, 2H), 3.11(t, J=6.0 Hz, 2H), 2.99(s, 3H), 2.84(s, 1H), 2.71—2.75(m, 1H), 1.12(d, J=6.6 Hz, 6H)	178.7, 140.1, 132.5, 129.1, 126.9, 49.6, 47.5, 41.5, 35.9, 30.5, 19.7, 19.1
13^a	7.28—7.85(m, 5H), 5.75(t, J=6.0 Hz, 1H), 3.68—3.79(m, 2H), 3.30(s, 3H), 3.21—3.29(m, 1H), 3.11—3.20(m, 2H), 1.39(d, J=7.2 Hz, 6H)	180.6, 139.3, 133.2, 129.5, 126.9, 117.8, 117.5, 54.7, 51.5, 42.8, 40.9, 32.9, 19.5

Fig.3 Structures of compounds 6—8

Fig.4 Structures of compounds 9—13

Fig.5 Molecular structure of compound 8a

Table 3 Crystal data and refinement parameters for compound 8a

Formula	C₁₇H₃₀IN₃O₂S	α/(°)	107.288(6)	θ Range /(°)	3.12—26.37
Formula weight	467.19	β/(°)	90.086(5)	Data/parameters/restraints	8857/533/106
Crystal size/mm³	0.31×0.23×0.11	γ/(°)	102.039(5)	GOF	1.050
Crystal system	Triclinic	V/nm³	2.165(2)	R₁[I>2σ(I)]	0.0630
Space group	P $1 ˉ$	Z	2	Reflections collected(R_int)	16995(0.0451)
a/nm	1.0562(5)	D_c/(g·cm^-3)	1.469	wR₂(all data)	0.2093
b/nm	1.3410(10)	F(000)	968.8
c/nm	1.6411(10)	μ/mm^-1	1.731

Table 3 Crystal data and refinement parameters for compound 8a

Formula	C₁₇H₃₀IN₃O₂S	α/(°)	107.288(6)	θ Range /(°)	3.12—26.37
Formula weight	467.19	β/(°)	90.086(5)	Data/parameters/restraints	8857/533/106
Crystal size/mm³	0.31×0.23×0.11	γ/(°)	102.039(5)	GOF	1.050
Crystal system	Triclinic	V/nm³	2.165(2)	R₁[I>2σ(I)]	0.0630
Space group	P $1 ˉ$	Z	2	Reflections collected(R_int)	16995(0.0451)
a/nm	1.0562(5)	D_c/(g·cm^-3)	1.469	wR₂(all data)	0.2093
b/nm	1.3410(10)	F(000)	968.8
c/nm	1.6411(10)	μ/mm^-1	1.731

Table 4 Selected bond distances(nm) and bond angles(°) for compound 8a

C7—C8	0.1509(8)	C11—C12	0.1533(16)	N2—S1	0.1601(5)	C10—N4	0.1332(8)
C8—N3	0.1462(8)	C12—C13	0.1461(19)	N4—C11	0.1419(10)	C10—C16	0.1524(9)
C9—N3	0.1452(9)	C13—C14	0.1460(19)	O1—S1	0.1419(5)	C16—C17	0.1524(11)
C10—N3	0.1331(8)	C7—N2	0.1472(8)	O2—S1	0.1423(5)	C16—C15	0.1531(10)
N3—C10—N4	118.9(6)	C10—C16—C15	110.6(6)	C10—N4—C11	132.3(7)	N2—C7—C8	110.3(5)
C1—C6—S1	120.6(6)	N4—C10—C16	121.6(6)	C10—N3—C9	118.8(6)	N3—C7—C8	111.7(5)
O1—S1—O2	118.9(3)	C17—C16—C10	112.1(7)	C10—N3—C8	125.6(5)	C7—N2—S1	120.7(5)
C5—C6—S1	119.8(6)	C17—C16—C15	114.8(7)	N3—C10—C16	119.4(6)	C9—N3—C8	115.5(5)

参考文献 29

[1]	Christensen K., E. , Mackenzie R., E. , Bioessays, 2006, 28, 595- 605
[2]	Methzler D. E., Biochemistry: The Chemical Reaction of Living Cells, Academic Press, New York, 1977, 493— 516
[3]	Vichers T., J. , Murta S. M., F. , Mandell M., A. , Beverley S., M. , Mol. Biochem. Para., 2009, 166, 142- 152
[4]	Ames T., D. , Rodionov D., A. , Weinberg, Z. , Breaker R., R. , Chem. Biol., 2010, 17, 681- 685
[5]	Page M., I. , Williams, A. , Enzyme, Mechanisms , The Royal Society of Chemistry Burlington, House , London, 1987, 429-450
[6]	Kallen R., G. , Jenchs W., P. , J. Biol. Chem., 1966, 241, 5845- 5849
[7]	Bieraugh, H. , Plemp, R. , Hiemstra H., C. , Pandit U., K. , Tetrahedron, 1983, 39, 3971- 3980
[8]	Pandit U., K. , Trav. Chim. Pays-Bas, 1988, 107, 111- 120
[9]	Pandit U., K. , Pure & Appl. Chem., 1994, 66, 759- 765
[10]	Xia C., Z. , Chen J., X. , Zhao B., J. , Wang H., X. , Kang C., M. , Ni Y., P. , Zhou P., W. , Synth. Commun., 2002, 32, 1129- 1134
[11]	陈建新, 潘继刚, 夏炽中, 程津培. 化学学报, 1998, 56, 819- 826
	Chen J., X. , Pan J., G. , Xia C., Z. , Cheng J., P. , Acta Chim. Sinica, 1998, 56, 819- 826
[12]	Li D., H. , Zhang Y., B. , Xia C., Z. , Guo, W. , Heterocycles, 2005, 65, 2893- 2900
[13]	Li D., H. , Hao J., S. , Deng, B. , Xia C., Z. , Guo, W. , Synth. Commun., 2004, 34, 3535- 3543
[14]	Yang B., Q. , Qiang J., L. , Bai Y., J. , Lu, J. , Shi, Z. , Chin. J. Chem., 2003, 21, 1210- 1212
[15]	Guo, Y. , Wu, X. , Li J., L. , Shi, Z. , Synth. Commun., 2005, 35, 2489- 2496
[16]	赵艳亲, 陈建新. 高等学校化学学报, 2012, 33( 12), 2670- 2675
	Zhao Y., Q. , Chen J., X. , Chem. J. Chinese Universities, 2012, 33( 12), 2670- 2675
[17]	Gunter, N. , Ulrich, E. , Gerhard, S. , J. Org. Chem., 1981, 46, 2824- 2828
[18]	Pool W., O. , Harwood H., J. , Ralston, A.W. , J. Am. Chem. Soc., 1937, 59, 178- 179
[19]	Pizzetti, M. , Luca E., D. , Petricci, E. , Porcheddu, A. , Taddei, M. , Adv. Synth. Catal., 2012, 354, 2453- 2464
[20]	Boiani, M. , Gonzalez, M. , Mini-rev. Med. Chem., 2005, 5, 409- 424
[21]	Evindar, G. , Batey R., A. , J. Org. Chem., 2006, 71, 1802- 1808
[22]	Fang, T. , Sun C., W. , Xu Y., Y. , Yuan, J. , Wang Y., F. , Xing J., H. , Chem. Res. Chinese Universities, 2014, 30( 6), 931- 936
[23]	江玉亮, 韩巧荣, 周文龙, 徐助雄, 王炳样. 高等学校化学学报, 2013, 34( 9), 2120- 2134
	Jiang Y., L. , Han Q., R. , Zhou W., L. , Xu Z., X. , Wang B., X. , Chem. J. Chinese Universities, 2013, 34( 9), 2120- 2134
[24]	Hein D., W. , Alheim R., J. , Leavitt J., J. , J. Am. Chem. Soc., 1957, 79, 427- 429
[25]	Wang, Y. , Sarris, K. , Sauer D., R. , Djuric S., W. , Tetrahedron Lett., 2006, 47, 4823- 4826
[26]	Gogoi, P. , Konwar, D. , Tetrahedron Lett., 2006, 47, 79- 82
[27]	Bahrami, K. , Khodaei M., M. , Naali, F. , J. Org. Chem., 2008, 73, 6835- 6837
[28]	Elizabeth A., J. , Kelly G., S. , Eric E., S. , J. Comb. Chem., 2000, 2, 441- 449
[29]	Viirre R., D. , Hudson R. H., E. , J. Org. Chem., 2003, 68, 1630- 1643