CN1174962C - Amidine compound and its preparing process - Google Patents
Amidine compound and its preparing process Download PDFInfo
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- CN1174962C CN1174962C CNB011131985A CN01113198A CN1174962C CN 1174962 C CN1174962 C CN 1174962C CN B011131985 A CNB011131985 A CN B011131985A CN 01113198 A CN01113198 A CN 01113198A CN 1174962 C CN1174962 C CN 1174962C
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Abstract
The present invention relates to an amidine compound and a preparing process thereof. The amidine compound is a fluoric amidine compound and has some potential physiological activities. Under a mild condition, raw materials with three components are synthesized into the amidine compound with various substituent groups in a single pot. The preparing process is a novel, convenient and high-efficient preparing process. The preparing process provides an effective synthetic method for sieving the precursor of medicine.
Description
The present invention relates to a class amidine compound, especially fluorine-containing amidine compound, and a kind of novel, easy, the preparation method efficiently of this compounds.The invention provides a kind ofly under utmost point mild conditions, set out, one pot of synthetic amidine compound with various substituted radicals by three component raw material.Compound of the present invention has some potential physiologically actives, for the screening of prodrug provides a kind of very effectively synthetic method.
A lot of amidine compounds have physiologically active (Matz, J. preferably; McDonald, J.; Wu, E.Appl.WO 2000073313 A1 7 Dec 2000,75 pp.Gomes-Cardoso, L.; Echevarria, A.; Aguiar-Alves, F.; Jansen, A.M.; Leon, L.L.Microbios, 1999,100,181-187.), so they are at agricultural chemicals, pharmaceutically have many uses, as can be used as antiphlogistic drug, insect repellent, medicine (Greenhill, the J.V. of hydragog(ue) and treatment diabetes and cardiovascular disorder; Lue, P.Prog.Med.Chem.1992,30,203.).Some amidines of discovered in recent years have antitumour activity, and have as anticarcinogen (Gambar, R.; Nastruzzi, C.Biochem.Pharmacol.1994,47,599.).Amidine compound can be used for synthetic nitrogen-containing heterocycle compound (Romero-Ortega, M. as the important intermediate of organic synthesis; Aviles, A.; Cruz, R.; Fuentes, A.; Gomez, R.M.; Plata, A.J.Org.Chem., 2000,65,7244-7247.Usui, H.; Watanable, Y.; Kanqo, M.J.Heterocycl.Chem.1993,30,551.).And amidine has catalytic activity preferably, can well a lot of organic reactions of catalysis, also can be used as solidifying agent (Aggarwal, the V.K. of cyclammonium resin and Polyurethane; Mereu, A.J.Org.Chem., 2000,65,7211-7212.).
Along with further expanding of the purposes of amidine, the research of its synthetic method has caused that also people more pay attention to (Choueiry, D.; Giraud, D.L.; Schotten, T.Patent Appl.WO2000078725 A1 28 Dec2000,68 pp.Lange, U.E.W.; Schafer, B.; Baucke, D.; Buschmann, E.; Mack, H.Tetrahedron Lett.1999,40,7067-7070.).Amidine compound synthetic has two kinds of methods commonly used.First kind is Pinner synthesis method, and promptly nitrile (nitriles) and alcohol reaction generate intermediate product amidates under the effect of acid, are generating amidine (Roger, R. with amine generation permutoid reaction then; Neilson, D.G.Chem.Rev.1961,61,179.Tidwell, R.R.; Fox, L.L.; Geratz, J.D.Biochem.Biophys.Acta.1976,445,729.).Reaction formula is as follows:
Second kind be by amide compound (amides) the heating condition under and POCl
3, PCl
5Or SOCl
2Effect, at first generate halo imines product (imidoyl chloride), and then and amine reaction and generate amidine (Ogener, J.I.Acta.Pol.Pharm.1986,43,191.Dubina, V.L.et al Zh.Org.Khim.1986,22,2590.).Reaction formula is as follows:
Very obviously above two kinds of methods respectively have its critical limitations: 1. they all are two-step reactions, and reaction treatment comparatively bothers like this, and therefore productive rate is restricted; 2. their used reagent is as acid, phosphorus oxychloride, phosphorus pentachloride, thionyl chloride etc., not only reaction substrate required to have better stability, and conversion unit is had relatively high expectations, as erosion resistance etc.; 3. big for environment pollution, especially second method will be used excessive phosphorous, chloro-containing reagent, and this can cause great pollution to environment.In environmental consciousness enhanced today day by day, this method can be restricted gradually.The method ortho-formiate method that other is comparatively commonly used, the amide acetals method, the sulfide oxidation method, carboxyl acid method etc., but they exist same shortcoming.Therefore be necessary very much to develop a kind of efficiently, oligosaprobic, gentle synthetic method.
Recently Saluste has reported by isonitrile, aryl bromide and secondary amine reflux in toluene and having realized by three component raw material set out one-step synthesis amidine compound (Saluste, C.G. under the effect of divalence palladium; Whity, R.J.; Furber, M.Angew.Chim.Int.Ed.2000,39,4156-4158.).Since nineteen ninety-five, multi-component reaction MCRs (Multicomponent Reactions) more and more is subject to people's attention (Domling, A.; Ugi, I.Angew.Chem.Int.Engl.Ed.2001,39,3168-3210.).MCRs compares with polystep reaction can save separating and purifying of many intermediates, therefore it has many conspicuous advantages, the viewpoint that meets Green Chemistry (Green Chemistry) and Atom economy (Atom Economy), requirement (Ideal Chemical Synthesis) (Wender, the P.A. that can meet the ideal chemosynthesis preferably; Handy, S.T.; Wright, D.L.Chem.Ind.1997,765.).
The object of the invention provides a class amidine compound, especially fluorine-containing amidine compound.
Another purpose of the present invention provides the synthetic method of such amidine compound.Set out, can generate a series of amidine compound by single step reaction under the room temperature by three component raw material.
Amidine compound molecular formula of the present invention is R
1R
2CHC (=NSO
2Y) NR
3R
4, have following structural formula:
R wherein
1Or R
2=H,, C
1-5Alkyl, replacement or unsubstituted phenyl ZPh-;
R
3Or R
4=C
1-5Alkyl, replacement or unsubstituted phenyl ZPh-,-(C
2H
4C
2H
4)-,-(C
2H
4OC
2H
4)-,-(C
2H
4CH
2C
2H
4)-,-(C
2H
4NHC
2H
4)-,-((C
2H
4N (CH
3) C
2H
4))-,-((C
2H
4N (iC
3H
7) C
2H
4))-or-(C
2H
4NPhC
2H
4)-.
Y=C
1-8Perfluoroalkyl C
nF
2n+1, n=1-8; C
2F
4O (C
2F
4)
mX, m=1-3; The phenyl C that polyfluoro replaces
6F
kH
5-k, k=1-5; Replace or unsubstituted phenyl ZPh-.
Above-described substituting group Z=H, C
1-4Alkyl or W; X is a halogen, as F, Cl, Br, I; W is X, OR, NH
2, NHR, NRR`, NO
2, R or R` are C
1-4Alkyl.
Above-mentioned amidine compound of the present invention can prepare by following method:
In organic solvent and under the room temperature, aldehyde R
1R
2CHCHO, secondary amine HNR
3R
4With triazo-compound YSO
2N
3Carried out complete 2-48 hour at room temperature reaction.In the slower response situation of some speed of response, add a certain amount of molecular sieve, not only this speed of response can be speeded, but also the productive rate of this reaction can be improved.The mol ratio of above-claimed cpd is respectively aldehyde in this reaction: secondary amine: nitrine=1～1.5: 1～1.5: 1.0.Recommend mol ratio to be respectively aldehyde: secondary amine: nitrine=1～1.1: 1～1.1: 1.0.
Adopt method of the present invention, look the difference of substrate and reaction times difference slightly, the result can obtain productive rate 67-95% preferably.Look the difference of substrate and reaction yield difference slightly generates corresponding amidine compound R
1R
2CHC (=NSO
2Y) NR
3R
4
For product is under the solid response situation, and its reaction system can removing desolvates gets final product through draining.Perhaps can obtain pure product through column chromatography or recrystallization again.
Reaction formula of the present invention is as follows:
This reaction response mild condition need not heat or cool off; Byproduct of reaction only is water and nitrogen, therefore environment is not had any pollution; This reaction has higher Atom economy, does not need to add chemical reagent; This reaction raw materials is easy to get and has variable very widely kind, so can synthesize a large amount of amidine compounds that contains different substituents group at short notice.Method of the present invention is a kind of method of suitable explained hereafter.
To help to understand the present invention by following embodiment, but not limit content of the present invention.
Embodiment 1
N`-(3-oxa--ω-iodo perfluoro pentane sulfuryl)-N, N-(3-oxa-cyclopentyl)-2-methyl-prop amidine synthetic
To isobutyric aldehyde (0.108g, 1.500mmol) and the morphine quinoline (0.131g, slowly drip in anhydrous ether solution 1.500mmol) (5mL) 3-oxa--ω-iodo perfluoro amyl group sulfonyl azide (0.612g, 1.363mmol), after the stirring at room 8 hours, the TLC demonstration reacts completely.Removing and desolvate, is that solvent recrystallization gets amidine class product (0.513g, 0.913mmol, 67%, Petroleum ether/EtOAc, 2: 1, R with sherwood oil (amount of ethyl acetate)
f=0.24).
White solid, fusing point 53-54 ℃.
IR(KBr)：ν＝2982(C-H)，1561(C＝N)，1442(SO
2)，1321，1220-1080(C-F).
1H?NMR：8＝3.83-3.78(8H，m)，3.64(1H，m)，1.39(6H，d，J?7.1Hz).
19F?NMR：-63.8(2F，s)，-80.5(2F，t，J?17Hz)，-84.8(2F，t，J?17Hz)，-116.1(2F，s).
MS：m/z(％)＝547(M
+-CH
3，0.69)，435(M
+-I，4.23)，219(M
+-R
f，20.43)，155(M
+- SO
2R
f，21.71)，86(C
4H
8NO
+，100.00).
Ultimate analysis, calculated value: C, 25.62; H, 2.67; N, 4.98%. measured value: C.25.98; H.2.73; N, 5.01%.
Embodiment 2
N`-(3-oxa--ω-iodo perfluoro pentane sulfuryl)-N, N-cyclobutyl-2-methyl-prop amidine synthetic
To isobutyric aldehyde (0.084g, 1.167mmol) and Pyrrolidine (0.083g, slowly drip in anhydrous ether solution 1.167mmol) (5mL) 3-oxa--ω-iodo perfluoro amyl group sulfonyl azide (0.523g, 1.164mmol), after the stirring at room 4 hours, the TLC demonstration reacts completely.Removing and desolvate, is eluent with the petrol ether/ethyl acetate, and column chromatography gets amidine class product (0.476g, 0.872mmol, 75%, Petroleum ether/EtOAc, 2: 1, R
f=0.19).
Colorless oil.
IR(KBr)：ν＝2981(C-H)，1547(C＝N)，1452(SO
2)，1220-1080(C-F).
1H?NMR：δ＝3.67(4H，m)，3.21(1H，m)，2.05(2H，m)，1.91(2H，m)，1.30(6H，d，J7.3Hz).
19F?NMR：-64.7(2F，s)，-80.9(2F，t，J?17Hz)，-85.4(2F，?2F，t，J?17Hz)，-116.4(2F，s).
MS：m/z(％)＝546(M
+，1.71)，227(IC
2F
4 +，2.10)，203(M
+-R
f，6.69)，70(C
4H
8N
+，40.89)，43(C
3H
7 +，100.00).
Ultimate analysis, calculated value: C, 26.37; H, 2.75; N, 5.13%. measured value: C.26.49; H.2.80; N, 5.06%.
Embodiment 3
N`-(perfluorinated butane sulfuryl)-N, N-cyclobutyl-2-methyl-prop amidine synthetic
To isobutyric aldehyde (0.131g, 1.819mmol) and Pyrrolidine (0.129g, slowly drip in anhydrous ether solution 1.819mmol) (5mL) the perfluoro butyl sulfonyl azide (0.591g, 1.818mmol), stirring at room is after 1 hour, TLC shows and reacts completely.Removing and desolvate, is eluent with the petrol ether/ethyl acetate, and column chromatography gets amidine class product (0.522g, 1.237mmol, 68%, Petroleum ether/EtOAc, 2: 1, R
f=0.27).
Colorless oil.
IR(KBr)：ν＝2981(C-H)，1546(C＝N)，1455(SO
2)，1321，1240-1100(C-F).
1H?NMR：δ＝3.71～3.64(4H，m)，3.22(1H，m)，2.09(2H，m)，1.95(2H，m)，1.28(6H，d，J?7.0Hz).
19F?NMR：-79.7(3F，s)，-109.3(2F，m)，-116.7(2F，m)，-122.1(2F，s).
MS：m/z(％)＝423(M
++1，31.08)，203(M
+-R
f，16.40)，70(C
4H
8N
+，100.00).
Ultimate analysis, calculated value: C, 34.12; H, 3.55; N, 6.64%. measured value: C.34.36; H.3.66; N, 6.69%.
Embodiment 4
N`-(perfluor benzene sulfuryl)-N, N-cyclobutyl-ethanamidine synthetic
To acetaldehyde (0.077g, 1.750mmol) and Pyrrolidine (0.124g, slowly drip in anhydrous ether solution 1.750mmol) (5mL) the perfluorophenyl sulfonyl azide (0.455g, 1.667mmol), stirring at room is after 10 hours, TLC shows and reacts completely.Removing and desolvate, is eluent with the petrol ether/ethyl acetate, and column chromatography gets amidine class product (0.530g, 1.550mmol, 93%, Petroleum ether/EtOAc, 2: 1, R
f=0.27).
Colorless oil.
IR(KBr)：ν＝2981(C-H)，1546(C＝N)，1455(SO
2)，1321，1240-1100(C-F).
1H?NMR：δ＝3.73～3.66(4H，m)，2.55(3H，s)，2.08(2H，m)，1.96(2H，m).
19F?NMR：-142.9(2F，d)，-155.5(1F，t)，-164.9(2F，t).
MS：m/z(％)＝342(M
+，20.56)，273(C
6F
5SO
2 +，31.20)，70(C
4H
8N
+，100.00)，69(CF
3 +，16.08).
Ultimate analysis, calculated value: C, 42.11; H, 3.22; N, 8.19%. measured value: C.42.36; H.3.41; N, 8.27%.
Embodiment 5
N`-(to the methylbenzene sulfuryl)-N, N-cyclobutyl-2-methyl-prop amidine synthetic
To isobutyric aldehyde (0.109g, 1.514mmol) and Pyrrolidine (0.108g, slowly drip in anhydrous ether solution 1.514mmol) (5mL) to the Methyl benzenesulfonyl nitrine (0.298g, 1.513mmol), stirring at room is after 12 hours, TLC shows and reacts completely.Removing and desolvate, is eluent with the petrol ether/ethyl acetate, and column chromatography gets amidine class product (0.367g, 1.250mmol, 83%, Petroleum ether/EtOAc, 2: 1, R
f=0.13).
White crystal, fusing point: 101-102 ℃.
IR(KBr)：ν＝3045，2981(C-H)，1522(C＝N)，1450(SO
2)，875，856，833.
1H?NMR：δ＝7.84(2H，d，J?7.9Hz)，7.24(2H，d，J?7.9Hz)，3.73(1H，m)，3.64-3.57(4H，m)，2.39(3H，s)，1.97(2H，t，J?6.7Hz)，1.84(2H，t，J?7.0Hz)，1.29(6H，d，J?7.0Hz).
MS：m/z(％)＝295(M
++1，1.47)，294(M
+，0.60)，155(Ts
+，18.16)，139(M
+-Ts，12.84)，91(C
7H
7 +，43.71)，70(C
4H
8N
+，100.00).
Ultimate analysis, calculated value: C, 61.22; H, 7.48; N, 9.52%. measured value: C.61.04; H.7.23; N, 9.45%.
Embodiment 6
N`-(normal hexane sulfuryl)-N, N-di-isopropyl-3-methyl fourth amidine synthetic
To isovaleric aldehyde (0.143g, 1.667mmol) and diisopropylamine (0.168g, slowly drip in anhydrous ether solution 1.667mmol) (5mL) to the n-hexyl sulfonyl azide (0.303g, 1.588mmol), stirring at room is after 24 hours, TLC shows and reacts completely.Removing and desolvate, is eluent with the petrol ether/ethyl acetate, and column chromatography gets amidine class product (0.464g, 1.397mmol, 88%, Petroleum ether/EtOAc, 2: 1, R
f=0.44).
Colorless oil.
IR(KBr)：ν＝2987(C-H)，1522(C＝N)，1444(SO
2)，1306，1220-1122(C-F).
1H?NMR：δ＝3.74(2H，m)，2.66(2H，t，J?7.1Hz)，2.43(2H，d，J?6.5Hz)，2.22(1H，m)，1.74-1.40(8H，m)，1.21(12H，d，J?6.4Hz)，0.92(6H，d，J?6.1Hz)，0.89(3H，t，J7.0Hz).
MS：m/z(％)＝333(M
++1，3.80)，332(M
+，10.20)，177(M
+-Ts，12.84)，149(C
6H
13SO
2 +，28.80)，100(C
6H
14N
+，100.00)，91(C
7H
7 +，36.22).
Ultimate analysis, calculated value: C, 61.33; H, 10.84; N, 8.43%.Measured value: C.61.27; H.10.70; N, 8.30%.
Embodiment 7
N`-(perfluorinated butane sulfuryl)-N, N-diethyl-2-methyl-prop amidine synthetic
To isobutyric aldehyde (0.131g, 1.819mmol) and diethylamide (0.129g, slowly drip in anhydrous ether solution 1.819mmol) (5mL) to the perfluoro butyl sulfonyl azide (0.563g, 1.732mmol), stirring at room is after 36 hours, TLC shows and reacts completely.Removing and desolvate, is eluent with the petrol ether/ethyl acetate, and column chromatography gets amidine class product (0.592g, 1.397mmol, 74%, Petroleum ether/EtOAc, 2: 1, R
f=0.38).
Colorless oil.
IR(KBr)：ν＝2991(C-H)，1542(C＝N)，1450(SO
2)，1348，1258-1080(C-F).
1H?NMR：δ＝3.74(1H，m)，3.55(2H，q，J?7.0Hz)，3.48(2H，q，J?7.0Hz)，1.33(3H，t，J7.0Hz)，1.28(6H，d，J?7.0Hz)，1.21(3H，t，J?7.0Hz).
MS：m/z(％)＝424(M
+，8.60)，283(C
4F
9SO
2 +，31.80)，141(M
+-C
4F
9SO
2，16.80)，72(C
4H
10N
+，100.00)，43(C
3H
7 +，45.66).
Ultimate analysis, calculated value: C, 33.96; H, 4.01; N, 6.60%. measured value: C.34.21; H.4.21; N, 6.81%.
Embodiment 8
Synthesizing of N`-(perfluorinated butane sulfuryl)-N-methyl-N-phenyl-benzene ethanamidine
To phenylacetic aldehyde (0.151g, 1.258mmol) and methylphenylamine (0.135g, slowly drip in anhydrous ether solution 1.258mmol) (5mL) to the perfluoro butyl sulfonyl azide (0.389g, 1.198mmol), after the stirring at room 12 hours, the TLC demonstration reacts completely.Removing and desolvate, is eluent with the petrol ether/ethyl acetate, and column chromatography gets amidine class product (0.521g, 1.030mmol, 86%, Petroleum ether/EtOAc, 3: 1, R
f=0.32).
Colorless oil.
IR(KBr)：ν＝2990(C-H)，1544(C＝N)，1445(SO
2)，1305，1240-1050(C-F).
1H?NMR：δ＝7.52(3H，m)，7.18(2H，m)，7.13(2H，m)，7.22(3H，m)，3.84(2H，s)，3.35(3H，s).
19F?NMR：-79.7(3F，s)，-109.3(2F，m)，-116.7(2F，m)，-122.1(2F，s).
MS：m/z(％)＝506(M
+，4.20)，283(C
4F
9SO
2 +，25.50)，141(M
+-C
4F
9SO
2，10.50)，72(C
4H
10N
+，100.00)，43(C
3H
7 +，31.08)，.
Ultimate analysis, calculated value: C, 45.06; H, 2.96; N, 5.53%. measured value: C.45.31; H.3.21; N, 5.71%.
Embodiment 9
N`-(3-oxa--ω-iodo perfluoro pentane sulfuryl)-N, N-(3-phenyl-3-nitrogen heterocyclic amyl group)-just own amidine synthetic
To n-hexyl aldehyde (0.164g, 1.608mmol) and the 4-phenylpiperazine (0.264g, slowly drip in anhydrous ether solution 1.608mmol) (5mL) 3-oxa--ω-iodo perfluoro pentane sulfonyl azide (0.688g, 1.531mmol), after the stirring at room 4 hours, the TLC demonstration reacts completely.Removing and desolvate, is eluent with the petrol ether/ethyl acetate, and column chromatography gets amidine class product (0.758g, 1.164mmol, 76%, Petroleum ether/EtOAc, 2: 1, R
f=0.42).
Colorless oil.
IR(KBr)：ν＝2985(C-H)，1559(C＝N)，1451(SO
2)，1298，1200-1050(C-F).
1H?NMR：δ＝7.22(2H，m)，6.82(2H，d，J?8.4Hz)，6.77(1H，m)，3.47-3.54(4H，m)，2.61(2H，t，J?7.0Hz)，2.44(2H，t，J?7.5Hz)，2.38(2H，t，J?7.5Hz)，1.66(2H，m)，1.40(4H，m)，0.88(3H，t，J?9.0Hz).
19F?NMR：-63.3(2F，s)，-80.2(2F，t，J?17Hz)，-84.4(2F，t，J?17Hz)，-115.8(2F，s).
MS：m/z(％)＝651(M
+，3.23)，524(M
+-I，8.22)，308(M
+-R
f，24.20)，244(M
+-SO
2R
f，30.56)，77(C
6H
5 +，100.00).
Ultimate analysis, calculated value: C, 36.87; H, 3.69; N, 4.30%. measured value: C.36.99; H.3.83; N, 5.42%.
Embodiment 10
N`-(trifyl)-N, N-(cyclopentyl)-synthesizing to the anisole ethanamidine
To p-methoxy phenylacetaldehyde (0.243g, 1.620mmol) and hexahydropyridine (0.138g, slowly drip in anhydrous ether solution 1.620mmol) (5mL) the trifluoromethyl sulfonyl azide (0.270g, 1.543mmol), after the stirring at room 8 hours, the TLC demonstration reacts completely.Removing and desolvate, is eluent with the petrol ether/ethyl acetate, and column chromatography gets amidine class product (0.404g, 1.111mmol, 72%, Petroleum ether/EtOAc, 2: 1, R
f=0.49).
Colorless oil.
IR(KBr)：ν＝2985(C-H)，1559(C＝N)，1451(SO
2)，1298，1200-1050(C-F).
1H?NMR：δ＝7.08(2H，d，J?7.0Hz)，7.00(2H，d，J?7.0Hz)，3.84(2H，s)，3.80(2H，t，J5.7Hz)，3.68(3H，s)，3.60(2H，t，J?5.7Hz)，1.65(6H，m).
19F?NMR：-76.5(3F，s).
MS：m/z(％)＝364(M
+，10.21)，231(M
+-SO
2R
f，32.70)，84(C
5H
10N
+，100.00)，69(CF
3 +，51.20).
Ultimate analysis, calculated value: C, 49.45, H, 5.22; N, 7.69%. measured value: C.49.22; H.5.01; N, 7.40%.
Embodiment 11
N`-(PFO alkylsulfonyl)-N, N-(dimethyl)-p-nitrophenyl ethanamidine synthetic
To p-nitrophenyl acetaldehyde (0.285g, 1.728mmol) and dimethyl amine (0.078g, slowly drip in anhydrous ether solution 1.728mmol) (5mL) the Perfluorononane sulfonyl azide (0.864g, 1.646mmol), after the stirring at room 48 hours, the TLC demonstration reacts completely.Removing and desolvate, is eluent with the petrol ether/ethyl acetate, and column chromatography gets amidine class product (0.897g, 1.333mmol, 81%, Petroleum ether/EtOAc, 2: 1, R
f=0.35).White solid, fusing point: 198-199 ℃.
IR(KBr)：ν＝2985(C-H)，1559(C＝N)，1451(SO
2)，1298，1200-1050(C-F).
1H?NMR：δ＝8.05(2H，d，J?8.4Hz)，7.37(2H，d，J?8.4Hz)，3.88(2H，s)，2.89(6H，s).
19F?NMR：-81.6(CF
3，s)，-113.8(CF
2，s)，-121.6(CF
2，s)，-122.3(C
4F
8，s)，-126.8(CF
2，s).
MS：m/z(％)＝673(M
+，0.82)，631(M
+-C
2H
5N，2.37)，254(M
+-R
f，16.70)，122(Ar
+，20.88)，69(CF
3 +，13.20)，42(C
2H
5N
+，100.00).
Ultimate analysis, calculated value: C, 32.10; H, 1.78; N, 6.24%. measured value: C.32.33; H.1.98; N, 6.43%.
Embodiment 12
N`-(3-oxa--ω-iodo perfluoro nonane alkylsulfonyl)-N, N-(3-methyl-3-nitrogen heterocyclic amyl group)-cumic aldehyde ethanamidine synthetic
To p-isopropyl phenylacetic aldehyde (0.231g, 1.425mmol) and 4-methylpiperazine (0.143g, 1.425mmol) anhydrous ether solution (5mL) in slowly drip 3-oxa--ω-iodo perfluoro nonane sulfonyl azide (0.881g, 1.357mmol), after the stirring at room 12 hours, the TLC demonstration reacts completely.Removing and to desolvate, is eluent with sherwood oil/methyl-formiate, column chromatography get amidine class product (1.072g, 1.240mmol, 87%, Petroleumether/EtOAc, 1-2: 1, R
f=0.39).
Colorless oil.
IR(KBr)：ν＝2985(C-H)，1559(C＝N)，1451(SO
2)，1298，1200-1050(C-F).
1H?NMR：δ＝7.30(2H，d，J?6.5Hz)，7.05(2H，d，J?6.5Hz)，3.47-3.54(4H，m)，3.30(2H，s)，2.85(1H，m)，2.44(4H，d，J?7.5Hz)，2.23(3H，s)，1.19(6H，d，J?7.0Hz).
19F?NMR：-80.5(CF
2，s)，-82.0(CF
2，s)，-115.0(CF
2，s)，-119.5(C
4F
8，m)，-124.6(CF
2，s).
MS：m/z(％)＝865(M
+，0.54)，322(M
+-R
f，10.24)，119(C
9H
11 +，32.18)，99(C
5H
11N
2 +，100.00).
Ultimate analysis, calculated value: C, 33.29; H, 2.77; N, 4.86%. measured value: C.33.67; H.2.99; N, 4.93%.
Embodiment 13
N`-(p-nitrophenyl sulfuryl)-N, N-di-n-butyl-synthesizing to the Dimethylaminobenzene ethanamidine
To Dimethylaminobenzene second (0.258g, 1.582mmol) and di-n-butyl amine (0.204g, slowly drip in anhydrous ether solution 1.582mmol) (5mL) the p-nitrophenyl sulfonyl azide (0.344g, 1.507mmol), after the stirring at room 36 hours, the TLC demonstration reacts completely.Removing and desolvate, is eluent with sherwood oil/ethyl formate, and column chromatography gets amidine class product (0.450g, 0.949mmol, 63%, Petroleum ether/EtOAc, 2: 1, R
f=0.27).
White crystal, fusing point: 186-187 ℃.
IR(KBr)：ν＝3045，2981(C-H)，?1522(C＝N)，1450(SO
2)，875，856，833.
1H?NMR：δ＝8.36(2H，d，J?8.5Hz)，7.75(2H，d，J?8.5Hz)，6.81(2H，d，J?8.4Hz)，6.72(2H，d，J?8.4Hz)，3.60(2H，q，J?7.2Hz)，3.50(2H，q，J?7.2Hz)，3.40(2H，s)，2.87(6H，s)，1.62(4H，m)，1.31(4H，m)，0.99(3H，t，J?7.2Hz)，0.92(3H，t，J?7.2Hz).
MS：m/z(％)＝474(M
+，10.22)，288(M
+-SO
2Ar，45.20)，128(C
8H
18N
+，68.96)，57(C
4H
9 +，100.00).
Ultimate analysis, calculated value: C, 60.76; H, 7.17; N, 11.81%. measured value: C.60.51; H.7.01; N, 11.54%.
Embodiment 14
N`-(to the methylbenzene sulfuryl)-N, N-(3-sec.-propyl-3-nitrogen heterocyclic amyl group)-2-methylbenzene ethanamidine synthetic
To 2-methyl phenylacetaldehyde (0.203g, 1.514mmol) and 4-sec.-propyl piperazine (0.194g, slowly drip in anhydrous ether solution 1.514mmol) (5mL) to the Methyl benzenesulfonyl nitrine (0.298g, 1.513mmol), after the stirring at room 12 hours, the TLC demonstration reacts completely.Removing and desolvate, is eluent with the petrol ether/ethyl acetate, and column chromatography gets amidine class product (0.753g, 1.250mmol, 77%, Petroleum ether/EtOAc, 2: 1, R
f=0.32).
White crystal, fusing point: 181-182 ℃.
IR(KBr)：ν＝3025，2989(C-H)，1528(C＝N)，1445(SO
2)，880，846，823.
1H?NMR：δ＝7.84(2H，d，J?7.9Hz)，7.32(2H，m)，7.24(2H，d，J?7.9Hz)，7.21(1H，m)，7.15(2H，d，J?8.3Hz)，4.98(1h，q，J?7.0Hz)，3.48-3.55(4H，m)，2.74(1H，m)，2.54-2.58(4H，m)，1.32(3H，d，J?7.0Hz)，1.13(6H，d，J?7.0Hz).
MS：m/z(％)＝414(M
++1，2.20)，413(M
+，3.82)，155(Ts
+，20.80)，258(M
+-Ts，32.84)，91(C
7H
7 +，69.78)，127(C
7H
15N
2 +，100.00).
Ultimate analysis, calculated value: C, 66.83; H, 7.51; N, 10.17%. measured value: C.66.97; H.7.70; N, 10.33%.
Claims (4)
1. amidine compound is characterized in that having following structural formula:
Wherein
R
1Or R
2=H, C
1-5Alkyl, replace or unsubstituted phenyl ZPh-;
R
3Or R
4=C
1-5Alkyl, replace or unsubstituted phenyl ZPh-,-(C
2H
4C
2H
4)-,-(C
2H
4OC
2H
4)-,-(C
2H
4CH
2C
2H
4)-, ,-((C
2H
4N (CH
3) C
2H
4))-,-((C
2H
4N (iC
3H
7) C
2H
4))-,-(C
2H
4NPhC
2H
4)-;
Y=C
1-8Perfluoroalkyl C
nF
2n+1, n=1-8; C
2F
4O (C
2F
4)
mX, m=1-3; The phenyl ZC that polyfluoro replaces
6F
kH
5-k, k=1-5;
Above-described substituting group, Z=H, C
1-4Alkyl or W; X is a halogen, F, Cl, Br or I; W is X, OR, NH
2, NHR, NRR` or NO
2R or R` are C
1-4Alkyl.
2, the preparation method of a kind of amidine compound as claimed in claim 1, it is characterized in that in organic solvent and room temperature under, aldehyde R
1R
2CHCHO, secondary amine HNR
3R
4With triazo-compound YSO
2N
3Mol ratio is an aldehyde: amine: nitrine=1～1.5: 1～1.5: 1.0 o'clock, reacted 2-48 hour, wherein R
1, R
2, R
3, R
4With Y according to claim 1.
3, the preparation method of a kind of amidine compound as claimed in claim 2 is characterized in that described aldehyde, secondary amine and triazo-compound mol ratio are aldehyde: amine: nitrine=1～1.1: 1～1.1: 1.0.
4, the preparation method of a kind of amidine compound as claimed in claim 2 is characterized in that desolventizing after the reaction, column chromatography or recrystallization.
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|---|---|---|---|
| CNB011131985A CN1174962C (en) | 2001-06-29 | 2001-06-29 | Amidine compound and its preparing process |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011131985A CN1174962C (en) | 2001-06-29 | 2001-06-29 | Amidine compound and its preparing process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1327981A CN1327981A (en) | 2001-12-26 |
| CN1174962C true CN1174962C (en) | 2004-11-10 |
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ID=4659940
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|---|---|---|---|
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| CN110078642B (en) * | 2019-05-30 | 2021-12-31 | 华侨大学 | Application of chlorodifluoromethane as C1 source in synthesis of amidine compounds |
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