Summary of the invention
The object of the invention is to design and synthesize a series of Diaryl propionyl-N-methyl hydroxamic acid (I) type urease inhibitor, on the basis of further investigation structure activity relationship, find the new urea enzyme inhibitors that activity is higher, toxic side effect is lower, and the method for making of Diaryl propionyl-N-methyl hydroxamic acid compound is provided.
Technical scheme of the present invention is as follows:
One class Diaryl propionyl-N-methyl hydroxamic acid compound, they have following general structure:
R in formula I
1, R
2, R
3, R
4, R
5, R
6, R
7and R
8definition take from following each group arbitrary group:
(1) R
2=R
3=R
4=R
5=R
6=R
7=R
8=H, R
1=F, Cl, Br, NO
2, OH, OMe, OEt or NH
2;
(2) R
1=R
3=R
4=R
5=R
6=R
7=R
8=H, R
2=F, Cl, Br, NO
2, OH, OMe, OEt or NH
2;
(3) R
1=R
2=R
4=R
5=R
6=R
7=R
8=H, R
3=F, Cl, Br, NO
2, OH, OMe, OEt or NH
2;
(4) R
2=R
3=R
4=R
5=R
6=R
7=H, R
1=R
8=F, Cl, Br, NO
2, OH, OMe, OEt or NH
2;
(5) R
1=R
3=R
4=R
5=R
6=R
7=H, R
2=R
7=F, Cl, Br, NO
2, OH, OMe, OEt or NH
2;
(6) R
1=R
2=R
4=R
5=R
7=R
8=H, R
3=R
6=CH
3or N (CH
3)
3;
(7) R
2=R
4=R
5=R
7=R
8=H, R
1=OH, R
3=OMe or O (CH
2)
7cH
3;
(8)R
1=R
4=R
5=R
6=R
7=R
8=H,R
2=R
3=CH
3;
(9)R
2=R
3=R
4=R
5=R
7=R
8=H,R
1=R
6=F;
(10)R
2=R
4=R
5=R
6=R
7=R
8=H,R
1=R
3=F;
(11)R
1=R
4=R
5=R
6=R
7=R
8=H,R
2=R
3=F;
(12) R
4=R
5=R
6=R
8=H, R
1=R
3=OH, R
2=R
7=OH or H;
(13)R
2=R
4R
5=R
6=R
7=R
8=H,R
1=Cl,R
3=NO
2;
(14)R
1=R
2=R
4=R
5=R
6=R
7=R
8=H,R
3=CH
3;
(15) R
2=R
4=R
5=R
6=R
7=R
8=H, R
1=NH
2, R
3=NO
2or Cl;
(16) R
2=R
3=R
4=R
5=R
6=R
7=H, R
1=OH, NH
2, NO
2, OMe or OEt, R
8=F, Cl or Br;
(17) R
2=R
3=R
4=R
5=R
6=R
8=H, R
1=OH, NH
2, NO
2or OMe, R
7=F, Cl or Br;
(18) R
2=R
3=R
4=R
5=R
6=R
8=H, R
1=OEt, R
7=Cl or Br;
(19) R
1=R
3=R
4=R
5=R
6=R
8=H, R
2=OH, R
7=F, Cl or Br.
Prepare a method for Diaryl propionyl-N-methyl hydroxamic acid series compound, it is made up of the following step substantially:
Step 1. is by 1-R
1-2-R
2-3-R
3-4-R
4substituted benzene joins BF
3et
2in O, be warming up between 40-50 DEG C, treat 1-R
1-2-R
2-3-R
3-4-R
4substituted benzene adds 2-R after dissolving
8-3-R
7-4-R
6-5-R
5substituted benzoic acid, the ratio of amount of substance: 1-R
1-2-R
2-3-R
31-R
1-2-R
2-3-R
3-4-R
4benzene: 2-R
8-3-R
7-4-R
6-5-R
5substituted benzoic acid: BF
3et
2o=1:(1 ~ 4): (60 ~ 100), are warming up between 65-110 DEG C and react 4 ~ 24h, react complete, pour in the aqueous solution of AcONa, stir 2 ~ 10h, suction filtration, washing, EtOH-H
2o recrystallization, obtains 1-R
1-2-R
2-3-R
3-4-R
4-2 '-R
8-3 '-R
7-4 '-R
6-5 '-R
5substituted diphenylamine base ketone (II);
Step 2. is by 1-R
1-2-R
2-3-R
3-4-R
4-2 '-R
8-3 '-R
7-4 '-R
6-5 '-R
5substituted diphenylamine base ketone (II), Zn powder, NH
4cl, ethyl bromoacetate are ground evenly together, the ratio of amount of substance: 1-R
1-2-R
2-3-R
3-4-R
4-2 '-R
8-3 '-R
7-4 '-R
6-5 '-R
5substituted diphenylamine base ketone (II): Zn:NH
4cl: ethyl bromoacetate=1:10:9:(1 ~ 5), room temperature pours saturated NH into after leaving standstill 10 ~ 24h
4cl solution, AcOEt extracts, anhydrous MgSO
4drying, boils off solvent, and with silica column purification, eluent volume ratio: AcOEt: sherwood oil=1:12 ~ 2:1, obtains 3-(2-R
1-3-R
2-4-R
3-5-R
4substituted-phenyl)-3-(2-R
8-3-R
7-4-R
6-5-R
5substituted-phenyl)-3-hydroxypropionate (III);
Step 3. is by 3-hydroxyl-3-(2-R
1-3-R
2-4-R
3-5-R
4substituted-phenyl)-3-(2-R
8-3-R
7-4-R
6-5-R
5substituted-phenyl) ethyl propionate (III) is dissolved in anhydrous methanol, then adds CH
3nHOHHCl, sodium methylate, the ratio of amount of substance is: 3-hydroxyl-3-(2-R
1-3-R
2-4-R
3-5-R
4substituted-phenyl)-3-(2-R
8-3-R
7-4-R
6-5-R
5substituted-phenyl) ethyl propionate (III): CH
3nHOHHCl:CH
3oNa=1:4:(2 ~ 9), stir 11 ~ 30h, boil off methyl alcohol, add deionized water, with AcOEt extraction, merge organic layer, MgSO
4drying, boils off solvent, and with silica column purification, eluent volume ratio: AcOEt: sherwood oil=1:10 ~ 3:1, obtains 3-hydroxyl-3-(2-R
1-3-R
2-4-R
3-5-R
4substituted-phenyl)-3-(2-R
8-3-R
7-4-R
6-5-R
5substituted-phenyl) propionyl-N-methyl hydroxamic acid (I), wherein said R
1, R
2, R
3, R
4, R
5, R
6, R
7and R
8definition identical with above-mentioned definition.
Embodiment
Further describe the present invention by following examples, but scope of the present invention should be noted not by any restriction of these embodiments.
The preparation of embodiment 1:3-(3-hydroxy phenyl)-3-(2,3,4-trihydroxy-phenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (50)
2.52g pyrogallol is joined 20ml BF
3et
2in O, then add 3.31g m-Salicylic acid, be warming up between 85 DEG C and react 15h, react complete, pour in the aqueous solution of AcONa, suction filtration, washing, EtOH-H
2o recrystallization, obtains 3-hydroxy phenyl-2,3,4-trihydroxy-phenyl ketone 3.78g, productive rate 77%;
By 3-hydroxy phenyl-2,3,4-trihydroxy-phenyl ketone 2.46g and 6.5g Zn powder, 4.82g NH
4cl, 4.45mL ethyl bromoacetate is ground evenly together.After room temperature leaves standstill 18h, pour saturated NH into
4cl solution, AcOEt extracts, anhydrous MgSO
4drying, boils off solvent, and with silica column purification, eluent volume ratio: AcOEt: sherwood oil=1:2, obtains 3-hydroxyl-3-(3-hydroxy phenyl)-3-(2,3,4-trihydroxy-phenyl) ethyl propionate, 2.17g, productive rate 65%;
Again by 1.67g3-hydroxyl-3-(3-hydroxy phenyl)-3-(2,3,4-trihydroxy-phenyl) ethyl propionate is dissolved in 30mL anhydrous methanol, adds CH under stirring
3nHOHHCl1.67g, CH
3oNa1.35g, stirring at room temperature 29h, add 10mL deionized water after boiling off methyl alcohol, AcOEt extracts, and merges organic layer, anhydrous MgSO
4drying, boils off solvent, silica gel (200-300 order) column chromatography purification, eluent volume ratio: AcOEt: sherwood oil=1:1, obtains white solid 3-hydroxyl-3-phenyl-3-(2,3,4-trihydroxy-phenyl) propionyl-N-methyl hydroxamic acid (50) 0.96g, productive rate 57%.Fusing point: 120-122 DEG C; EIMSm/z:335 [M
+]; IR(KBr) cm
-1: 2768(OH), 3021(NH);
1h NMR(DMSO-d
6) δ ppm:3.16(s, 2H), 3.29(s, 3H), 3.67(s, 1H), 5.76(s, 4H) and, 6.85(d, 1H), 7.01(d, 1H) and, 7.26(dd, 1H), 7.33(m, 3H) and, 8.21(s, 1H), 10.32(s, 1H).
Embodiment 2:
By the method that embodiment 1 is similar, be raw material with the phenylformic acid of different replacement forms and benzene, synthesized the Diaryl propionyl-N-methyl hydroxamic acid series compound 1 ~ 86 listed by table 1.
Each R group of Diaryl propionyl-N-methyl hydroxamic acid series compound in table 1 general formula I
Sequence number |
R
1 |
R
2 |
R
3 |
R
4 |
R
5 |
R
6 |
R
7 |
R
8 |
1 |
F |
H |
H |
H |
H |
H |
H |
H |
2 |
Cl |
H |
H |
H |
H |
H |
H |
H |
3 |
Br |
H |
H |
H |
H |
H |
H |
H |
4 |
NO
2 |
H |
H |
H |
H |
H |
H |
H |
5 |
OH |
H |
H |
H |
H |
H |
H |
H |
6 |
OMe |
H |
H |
H |
H |
H |
H |
H |
7 |
OEt |
H |
H |
H |
H |
H |
H |
H |
8 |
NH
2 |
H |
H |
H |
H |
H |
H |
H |
9 |
H |
F |
H |
H |
H |
H |
H |
H |
10 |
H |
Cl |
H |
H |
H |
H |
H |
H |
11 |
H |
Br |
H |
H |
H |
H |
H |
H |
12 |
H |
NO
2 |
H |
H |
H |
H |
H |
H |
13 |
H |
OH |
H |
H |
H |
H |
H |
H |
Sequence number |
R
1 |
R
2 |
R
3 |
R
4 |
R
5 |
R
6 |
R
7 |
R
8 |
14 |
H |
OMe |
H |
H |
H |
H |
H |
H |
15 |
H |
OEt |
H |
H |
H |
H |
H |
H |
16 |
H |
NH
2 |
H |
H |
H |
H |
H |
H |
17 |
H |
H |
F |
H |
H |
H |
H |
H |
18 |
H |
H |
Cl |
H |
H |
H |
H |
H |
19 |
H |
H |
Br |
H |
H |
H |
H |
H |
20 |
H |
H |
NO
2 |
H |
H |
H |
H |
H |
21 |
H |
H |
OH |
H |
H |
H |
H |
H |
22 |
H |
H |
OMe |
H |
H |
H |
H |
H |
23 |
H |
H |
OEt |
H |
H |
H |
H |
H |
24 |
H |
H |
NH
2 |
H |
H |
H |
H |
H |
25 |
F |
H |
H |
H |
H |
H |
H |
F |
26 |
Cl |
H |
H |
H |
H |
H |
H |
Cl |
27 |
Br |
H |
H |
H |
H |
H |
H |
Br |
28 |
NO
2 |
H |
H |
H |
H |
H |
H |
NO
2 |
29 |
OH |
H |
H |
H |
H |
H |
H |
OH |
30 |
OMe |
H |
H |
H |
H |
H |
H |
OMe |
31 |
OEt |
H |
H |
H |
H |
H |
H |
OEt |
32 |
NH
2 |
H |
H |
H |
H |
H |
H |
NH
2 |
33 |
H |
F |
H |
H |
H |
H |
F |
H |
34 |
H |
Cl |
H |
H |
H |
H |
Cl |
H |
35 |
H |
Br |
H |
H |
H |
H |
Br |
H |
36 |
H |
NO
2 |
H |
H |
H |
H |
NO
2 |
H |
37 |
H |
OH |
H |
H |
H |
H |
OH |
H |
38 |
H |
OMe |
H |
H |
H |
H |
OMe |
H |
39 |
H |
OEt |
H |
H |
H |
H |
OEt |
H |
40 |
H |
NH
2 |
H |
H |
H |
H |
NH
2 |
H |
Sequence number |
R
1 |
R
2 |
R
3 |
R
4 |
R
5 |
R
6 |
R
7 |
R
8 |
41 |
H |
H |
CH
3 |
H |
H |
CH
3 |
H |
H |
42 |
H |
H |
N(CH
3)
2 |
H |
H |
N(CH
3)
2 |
H |
H |
43 |
OH |
H |
OCH
2(CH
2)
6CH
3 |
H |
H |
H |
H |
H |
44 |
H |
CH
3 |
CH
3 |
H |
H |
H |
H |
H |
45 |
OH |
H |
OMe |
H |
H |
H |
H |
H |
46 |
F |
H |
H |
H |
H |
F |
H |
H |
47 |
F |
H |
F |
H |
H |
H |
H |
H |
48 |
H |
F |
F |
H |
H |
H |
H |
H |
49 |
OH |
OH |
OH |
H |
H |
H |
OH |
H |
50 |
OH |
H |
OH |
H |
H |
H |
H |
H |
51 |
Cl |
H |
NO
2 |
H |
H |
H |
H |
H |
52 |
H |
H |
CH
3 |
H |
H |
H |
H |
H |
53 |
NH
2 |
H |
NO
2 |
H |
H |
H |
H |
H |
54 |
NH
2 |
H |
Cl |
H |
H |
H |
H |
H |
55 |
OH |
H |
H |
H |
H |
H |
H |
F |
56 |
OH |
H |
H |
H |
H |
H |
H |
Cl |
57 |
OH |
H |
H |
H |
H |
H |
H |
Br |
58 |
NH
2 |
H |
H |
H |
H |
H |
H |
F |
59 |
NH
2 |
H |
H |
H |
H |
H |
H |
Cl |
60 |
NH
2 |
H |
H |
H |
H |
H |
H |
Br |
61 |
NO
2 |
H |
H |
H |
H |
H |
H |
F |
62 |
NO
2 |
H |
H |
H |
H |
H |
H |
Cl |
63 |
NO
2 |
H |
H |
H |
H |
H |
H |
Br |
64 |
OMe |
H |
H |
H |
H |
H |
H |
F |
65 |
OMe |
H |
H |
H |
H |
H |
H |
Cl |
66 |
OMe |
H |
H |
H |
H |
H |
H |
Br |
67 |
OEt |
H |
H |
H |
H |
H |
H |
F |
Sequence number |
R
1 |
R
2 |
R
3 |
R
4 |
R
5 |
R
6 |
R
7 |
R
8 |
68 |
OEt |
H |
H |
H |
H |
H |
H |
Cl |
69 |
OEt |
H |
H |
H |
H |
H |
H |
Br |
70 |
OH |
H |
H |
H |
H |
H |
Cl |
H |
71 |
OH |
H |
H |
H |
H |
H |
Br |
H |
72 |
OH |
H |
H |
H |
H |
H |
F |
H |
73 |
NH
2 |
H |
H |
H |
H |
H |
Cl |
H |
74 |
NH
2 |
H |
H |
H |
H |
H |
Br |
H |
75 |
NH
2 |
H |
H |
H |
H |
H |
F |
H |
76 |
NO
2 |
H |
H |
H |
H |
H |
Cl |
H |
77 |
NO
2 |
H |
H |
H |
H |
H |
Br |
H |
78 |
NO
2 |
H |
H |
H |
H |
H |
F |
H |
79 |
OMe |
H |
H |
H |
H |
H |
Cl |
H |
80 |
OMe |
H |
H |
H |
H |
H |
Br |
H |
81 |
OMe |
H |
H |
H |
H |
H |
F |
H |
82 |
OEt |
H |
H |
H |
H |
H |
Cl |
H |
83 |
OEt |
H |
H |
H |
H |
H |
Br |
H |
84 |
H |
OEt |
H |
H |
H |
H |
F |
H |
85 |
H |
OEt |
H |
H |
H |
H |
Cl |
H |
86 |
H |
OEt |
H |
H |
H |
H |
Br |
H |
Note: initial feed is all purchased from aldrich company
Embodiment 3: the Inhibiting enzyme activity of compound
25 μ LJack bean(sword beans are added in 96 orifice plates) urease (4U) and 25 μ L(1mM) solution of test compound, 2h is cultivated at 37 DEG C, then the phosphoric acid buffer 55 μ L containing 100mM urea and 100mM is added, 15min is cultivated at 30 DEG C, add 45 μ L phenol reagents (containing phenol 1% and the mixing solutions containing Sodium Nitroprusside 0.005%) and 70 μ L alkali reagents (mixing solutions containing the NaOCl of NaOH0.5% and 0.1% reactive chlorine), after at room temperature placing 50min, measure the OD value under 630nm by microplate reader, percent inhibition is calculated as follows:
All tests are all carry out (the K of 0.01M in the solution of 8.2 at pH
2hPO
4, the LiCl of the EDTA of 1mM, 0.01M), active height is with half inhibiting rate IC
50represent, IC
50less, the activity of this compound is higher, the results are shown in Table 2.
Result shows: part Diaryl propionyl-N-methyl hydroxamic acid series compound of the present invention has good inhibit activities to urease, and some are higher than the activity of positive control N-acetylhydroxylamine.
Table 2 Diaryl propionyl-N-methyl hydroxamic acid series compound is to the restraining effect (IC of sword bean urease
50)
Result shows, compound 3,15,23,32,39,43,50,57,65,69,75,80 pairs of sword bean ureases have significant restraining effect, and restraining effect comparatively N-acetylhydroxylamine is higher, active best 212 times that reach N-acetylhydroxylamine.
The above embodiment of the present invention shows: in the Diaryl propionyl-N-methyl hydroxamic acid series compound of synthesis, the Urease inhibitor effect of a part is higher than positive control N-acetylhydroxylamine, the anxious poison experiment of rat is shown, it is the non-toxic of States Pharmacopoeia specifications that the dosage of compound 15,32,50,69,80 reaches this dosage of 5g/kg() time, do not find that rat has signs of toxicity, therefore, under normal dose, they are safe as medicinal application.
The fusing point of compound 1 ~ 86, mass spectrum, infrared and nucleus magnetic hydrogen spectrum data:
3-phenyl-3-(2-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (1)
Mp137-139℃;EIMS m/z:289[M
+];IR(KBr)cm
-1:2761(OH),3025(NH);
1H NMR(DMSO-d
6)δppm:3.20(s,2H),3.28(s,3H),3.60(s,1H),7.21~7.28(m,1H),7.46~7.53(m,6H),7.53~7.71(m,2H),8.21(s,1H),10.25(s,1H)。
3-phenyl-3-(2-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (2)
Mp142-144℃;EIMS m/z:305[M
+];IR(KBr)cm
-1:2764(OH),3023(NH);
1H NMR(DMSO-d
6)δppm:3.17(s,2H),3.29(s,3H),3.57(s,1H),7.33~7.40(m,1H),7.45~7.53(m,5H),7.53~7.61(m,2H),7.82~7.90(m,1H),8.25(s,1H),10.23(s,1H)。
3-phenyl-3-(2-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (3)
Mp154-156℃;EIMS m/z:335[M
+];IR(KBr)cm
-1:2765(OH),3027(NH);
1H NMR(DMSO-d
6)δppm:3.18(s,2H),3.30(s,3H),3.58(s,1H),7.36~7.42(m,2H),7.45~7.51(m,4H),7.55~7.63(m,2H),7.63~7.71(m,1H),8.23(s,1H),10.24(s,1H)。
3-phenyl-3-(2-nitrophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (4)
Mp166-167℃;EIMS m/z316[M
+];IR(KBr)cm
-1:2768(OH),3026(NH);
1H NMR(DMSO-d
6)δppm:3.18(s,2H),3.31(s,3H),3.56(s,1H),7.42~7.50(m,3H),7.54~7.62(m,2H),7.71~7.77(m,2H),7.82~7.88(m,1H),8.30~8.41(m,2H),10.20(s,1H)。
3-phenyl-3-(2-hydroxybenzene)-3-hydroxyl propionyl-N-methyl hydroxamic acid (5)
Mp138-140℃;EIMS m/z:287[M
+];IR(KBr)cm
-1:2765(OH),3029(NH);
1H NMR(DMSO-d
6)δppm:3.17(s,2H),3.30(s,3H),3.60(s,1H),5.48(s,1H),7.02~7.17(m,2H),7.39~7.47(m,2H),7.48~7.53(m,3H),7.57~7.61(m,2H),8.22(s,1H),10.20(s,1H)。
3-phenyl-3-(2-methoxyl group base phenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (6)
Mp147-149℃;EIMS m/z:301[M
+];IR(KBr)cm
-1:2766(OH),3025(NH);
1H NMR(DMSO-d
6)δppm:3.18(s,2H),3.29(s,3H),3.64(s,1H),4.04(s,3H),7.15~7.22(m,3H),7.36~7.40(m,1H),7.45~7.50(m,3H),7.54~7.63(m,2H),8.24(s,1H),10.22(s,1H)。
3-phenyl-3-(2-ethoxyl phenenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (7)
Mp170-172℃;EIMS m/z:315[M
+];IR(KBr)cm
-1:2767(OH),3025(NH);
1H NMR(DMSO-d
6)δppm:1.18(t,3H),3.19(s,2H),3.28(s,3H),3.39(m,2H),3.64(s,1H),7.17~7.23(m,3H),7.36~7.40(m,1H),7.46~7.51(m,3H),7.55~7.63(m,2H),8.22(s,1H),10.23(s,1H)。
3-phenyl-3-(2-aminophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (8)
Mp131-133℃;EIMS m/z:286[M
+];IR(KBr)cm
-1:2768(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:3.18(s,2H),3.27(s,3H),3.62(s,1H),6.53(s,2H),6.91~6.97(m,2H),7.24~7.30(m,2H),7.47~7.53(m,3H),7.57~7.63(m,2H),8.22(s,1H),10.24(s,1H)。
3-phenyl-3-(3-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (9)
Mp139-141℃;EIMS m/z289[M
+];IR(KBr)cm
-1:2765(OH),3029(NH);
1H NMR(DMSO-d
6)δppm:3.17(s,2H),3.31(s,3H),3.63(s,1H),7.09(t,1H),7.32~7.40(m,2H),7.48~7.55(m,4H),7.55~7.62(m,2H),8.21(s,1H),10.23(s,1H)。
3-phenyl-3-(3-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (10)
Mp162-164℃;EIMS m/z:305[M
+];IR(KBr)cm
-1:2762(OH),3029(NH);
1H NMR(DMSO-d
6)δppm:3.19(s,2H),3.29(s,3H),3.63(s,1H),7.47~7.55(m,5H),7.58~7.63(m,3H),7.74(t,1H),8.24(s,1H),10.20(s,1H)。
3-phenyl-3-(3-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (11)
Mp175-177℃;EIMS m/z349[M
+];IR(KBr)cm
-1:2763(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:3.17(s,2H),3.29(s,3H),3.68(s,1H),7.33~7.40(m,1H),7.45~7.52(m,4H),7.54~7.60(m,2H),7.62~7.70(m,2H),8.21(s,1H),10.22(s,1H)。
3-phenyl-3-(3-nitrophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (12)
Mp169-170℃;EIMS m/z316[M
+];IR(KBr)cm
-1:2761(OH),3026(NH);
1H NMR(DMSO-d
6)δppm:3.17(s,2H),3.31(s,3H),3.67(s,1H),7.42~7.50(m,3H),7.53~7.61(m,3H),7.81~7.87(m,1H),7.92~7.96(m,1H),8.20(s,1H),8.41~8.46(m,1H),10.21(s,1H)。
3-phenyl-3-(3-hydroxy phenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (13)
Mp149-151℃;EIMS m/z287[M
+];IR(KBr)cm
-1:2765(OH),3029(NH);
1H NMR(DMSO-d
6)δppm:3.16(s,2H),3.29(s,3H),3.68(s,1H),5.47(s,1H),6.97-7.05(m,1H),7.11~7.18(m,1H),7.26~7.33(m,1H),7.35~7.43(m,1H),7.44~7.50(m,3H),7.58~7.65(m,2H),8.21(s,1H),10.21(s,1H)。
3-phenyl-3-(3-p-methoxy-phenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (14)
Mp160-162℃;EIMS m/z301[M
+];IR(KBr)cm
-1:2760(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:3.17(s,2H),3.31(s,3H),3.64(s,1H),4.13(s,3H),7.12~7.19(m,2H),7.25~7.32(m,1H),7.35~7.41(m,1H),7.47~7.53(m,3H),7.57~7.62(m,2H),8.22(s,1H)10.24(s,1H)。
3-phenyl-3-(3-ethoxyl phenenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (15)
Mp182-184℃;EIMS m/z315[M
+];IR(KBr)cm
-1:2764(OH),3022(NH);
1H NMR(DMSO-d
6)δppm:1.16(t,3H),3.17(s,2H),3.31(s,3H),3.41-3.54(m,2H),3.68(s,1H),7.07~7.13(m,2H),7.29(s,1H),7.47~7.54(m,4H),7.57~7.64(m,2H),8.23(s,1H)10.25(s,1H)。
3-phenyl-3-(3-aminophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (16)
Mp144-146℃;EIMS m/z:286[M
+];IR(KBr)cm
-1:2766(OH),3025(NH);
1H NMR(DMSO-d
6)δppm:3.15(s,2H),3.29(s,3H),3.67(s,1H),6.81(s,2H),7.13~7.20(m,3H),7.29~7.31(m,1H),7.47~7.55(m,3H),7.57~7.64(m,2H),8.21(s,1H)10.23(s,1H)。
3-phenyl-3-(4-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (17)
Mp137-139℃;EIMS m/z:289[M
+];IR(KBr)cm
-1:2764(OH),3026(NH);
1H NMR(DMSO-d
6)δppm:3.12(s,2H),3.29(s,3H),3.66(s,1H),7.32(t,2H),7.45~7.53(m,5H),7.57~7.63(m,2H),8.22(s,1H),10.22(s,1H)。
3-phenyl-3-(4-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (18)
Mp144-145℃;EIMS m/z:305[M
+];IR(KBr)cm
-1:2764(OH),3022(NH);
1H NMR(DMSO-d
6)δppm:3.10(s,2H),3.30(s,3H),3.69(s,1H),7.34(t,2H),7.45~7.52(m,3H),7.62(t,2H),7.57~7.66(m,2H),8.26(s,1H),10.23(s,1H)。
3-phenyl-3-(4-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (19)
Mp186-188℃;EIMS m/z:349[M
+];IR(KBr)cm
-1:2768(OH),3022(NH);
1H NMR(DMSO-d
6)δppm:3.12(s,2H),3.26(s,3H),3.69(s,1H),7.33(t,2H),7.45~7.53(m,3H),7.59~7.68(m,2H),8.12(t,2H),8.24(s,1H),10.24(s,1H)。
3-phenyl-3-(4-nitrophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (20)
Mp165-167℃;EIMS m/z:316[M
+];IR(KBr)cm
-1:2768(OH),3023(NH);
1H NMR(DMSO-d
6)δppm:3.19(s,2H),3.29(s,3H),3.66(s,1H),7.45~7.52(m,3H),7.57~7.63(m,2H),7.92(t,2H),8.22(s,1H),8.32(t,2H),10.25(s,1H)。
3-phenyl-3-(4-hydroxy phenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (21)
Mp131-133℃;EIMS m/z:287[M
+];IR(KBr)cm
-1:2765(OH),3026(NH);
1H NMR(DMSO-d
6)δppm:3.19(s,2H),3.26(s,3H),3.68(s,1H),5.75(s,1H),6.92(t,2H),7.36(t,2H),7.46~7.53(m,3H),7.57~7.63(m,2H),8.22(s,1H),10.21(s,1H)。
3-phenyl-3-(4-p-methoxy-phenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (22)
Mp138-139℃;EIMS m/z:301[M
+];IR(KBr)cm
-1:2764(OH),3027(NH);
1H NMR(DMSO-d
6)δppm:3.18(s,2H),3.29(s,3H),3.69(s,1H),4.19(s,3H),7.13(t,2H),7.39(t,2H),7.44~7.50(m,3H),7.57~7.64(m,2H),8.22(s,1H),10.23(s,1H)。
3-phenyl-3-(4-ethoxyl phenenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (23)
Mp140-142℃;EIMS m/z:315[M
+];IR(KBr)cm
-1:2762(OH),3027(NH);
1H NMR(DMSO-d
6)δppm:1.19(t,3H),3.17(s,2H),3.31(s,3H),3.42~3.50(m,2H),3.68(s,1H),7.13(t,2H),7.37(t,2H),7.46~7.54(m,3H),7.57~7.63(m,2H),8.24(s,1H),10.21(s,1H)。
3-phenyl-3-(4-aminophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (24)
Mp132-134℃;EIMS m/z:286[M
+];IR(KBr)cm
-1:2767(OH),3029(NH);
1H NMR(DMSO-d
6)δppm:3.17(s,2H),3.31(s,3H),3.68(s,1H),6.57(s,2H),7.29(t,2H),7.44~7.54(m,3H),7.58~7.62(m,2H),7.88(t,2H),8.22(s,1H),10.24(s,1H)。
3,3-bis-(2-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (25)
Mp195-197℃;EIMS m/z:307[M
+];IR(KBr)cm
-1:2765(OH),3027(NH);
1H NMR(DMSO-d
6)δppm:3.15(s,2H),3.29(s,3H),3.66(s,1H),7.29~7.35(m,2H),7.45~7.52(m,2H),7.76~7.82(m,2H),7.89~7.93(m,2H),8.24(s,1H),10.23(s,1H)。
3,3-bis-(2-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (26)
Mp203-205℃;EIMS m/z:339[M
+];IR(KBr)cm
-1:2760(OH),3028(NH);
1H NMR(DMSO-d
6)δppm:3.17(s,2H),3.31(s,3H),3.68(s,1H),7.34~7.42(m,2H),7.48~7.51(m,4H),7.86~7.93(m,2H),8.21(s,1H),10.24(s,1H)。
3,3-bis-(2-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (27)
Mp218-219℃;EIMS m/z:426[M
+];IR(KBr)cm
-1:2768(OH),3026(NH);
1H NMR(DMSO-d
6)δppm:3.17(s,2H),3.30(s,3H),3.68(s,1H),7.34~7.40(m,4H),7.48~7.53(m,2H),7.75~7.83(m,2H),8.21(s,1H),10.21(s,1H)。
3,3-bis-(2-nitrophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (28)
Mp212-214℃;EIMS m/z:361[M
+];IR(KBr)cm
-1:2762(OH),3023(NH);
1H NMR(DMSO-d
6)δppm:3.17(s,2H),3.29(s,3H),3.69(s,1H),7.81~7.88(m,4H),795~804(m,2H),831~839(m,3H),1023(s,1H)。
3,3-bis-(2-hydroxy phenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (29)
Mp179-181℃;EIMS m/z303[M
+];IR(KBr)cm
-1:2763(OH),3026(NH);
1H NMR(DMSO-d
6)δppm:3.19(s,2H),3.29(s,3H),3.69(s,1H),5.78(s,2H),7.19(t,4H),7.35~7.42(m,4H),8.26(s,1H),10.23(s,1H)。
3,3-bis-(2-p-methoxy-phenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (30)
Mp213-215℃;EIMS m/z:331[M
+];IR(KBr)cm
-1:2764(OH),3026(NH);
1H NMR(DMSO-d
6)δppm:3.17(s,2H),3.27(s,3H),3.68(s,1H),4.14(s,6H),7.11~7.20(m,6H),7.35~7.40(m,2H),8.26(s,1H),10.22(s,1H)。
3,3-bis-(2-ethoxyl phenenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (31)
Mp217-219℃;EIMS m/z:359[M
+];IR(KBr)cm
-1:2766(OH),3029(NH);
1H NMR(DMSO-d
6)δppm:1.21(t,6H),3.17(s,2H),3.27(s,3H),3.42~3.47(m,4H),3.69(s,1H),7.11~7.20(m,6H),7.35~7.43(m,2H),8.26(s,1H),10.23(s,1H)。
3,3-bis-(2-aminophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (32)
Mp1384-186℃;EIMS m/z301[M
+];IR(KBr)cm
-1:2763(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:3.18(s,2H),3.27(s,3H),3.69(s,1H),6.63(s,4H),6.92~7.01(m,4H),7.38~7.44(m,4H),8.26(s,1H),10.25(s,1H)。
3,3-bis-(3-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (33)
Mp190-192℃;EIMS m/z307[M
+];IR(KBr)cm
-1:2768(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:3.16(s,2H),3.29(s,3H),3.72(s,1H),7.21(t,2H),7.33~7.39(m,2H),7.40~7.47(m,2H),7.48~7.54(m,2H),8.28(s,1H),10.22(s,1H)。
3,3-bis-(3-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (34)
Mp204-206℃;EIMS m/z339[M
+];IR(KBr)cm
-1:2764(OH),3021(NH);
1H NMR(DMSO-d
6)δppm:3.15(s,2H),3.29(s,3H),3.65(s,1H),7.21(t,2H),7.31~7.36(m,2H),7.40~7.47(m,2H),7.48~7.54(m,2H),8.26(s,1H),10.20(s,1H)。
3,3-bis-(3-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (35)
Mp220-222℃;EIMS m/z:428[M
+];IR(KBr)cm
-1:2765(OH),3020(NH);
1H NMR(DMSO-d
6)δppm:3.15(s,2H),3.29(s,3H),3.65(s,1H),7.33~7.42(m,2H),7.58~7.63(m,2H),7.72~7.78(m,4H),8.26(s,1H),10.23(s,1H)。
3,3-bis-(3-nitrophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (36)
Mp167-169℃;EIMS m/z361[M
+];IR(KBr)cm
-1:2764(OH),3027(NH);
1H NMR(DMSO-d
6)δppm:3.18(s,2H),3.32(s,3H),3.69(s,1H),7.85~7.93(m,4H),8.17(d,2H),8.28(s,1H),8.34(dd,2H),10.24(s,1H)。
3,3-bis-(3-hydroxy phenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (37)
Mp166-168℃;EIMS m/z:303[M
+];IR(KBr)cm
-1:2763(OH),3025(NH);
1H NMR(DMSO-d
6)δppm:3.19(s,2H),3.29(s,3H),3.69(s,1H),5.79(s,2H),7.02~7.11(m,2H),7.17~7.25(m,4H),7.46~7.53(m,2H),8.28(s,1H),10.23(s,1H)。
3,3-bis-(3-p-methoxy-phenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (38)
Mp181-183℃;EIMS m/z331[M
+];IR(KBr)cm
-1:2768(OH),3023(NH);
1H NMR(DMSO-d
6)δppm:3.16(s,2H),3.33(s,3H),3.67(s,1H),4.19(s,6H),7.02~7.11(m,4H),7.28~7.36(m,2H),7.46~7.52(m,2H),8.29(s,1H),10.27(s,1H)。
3,3-bis-(3-ethoxyl phenenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (39)
Mp176-178℃;EIMS m/z359[M
+];IR(KBr)cm
-1:2763(OH),3021(NH);
1H NMR(DMSO-d
6)δppm:1.24(t,6H),3.16(s,2H),3.26(s,3H),3.67(s,1H),4.45~4.53(m,4H),7.02~7.13(m,4H),7.28~7.36(m,2H),7.46~7.52(m,2H),8.23(s,1H),10.24(s,1H)。
3,3-bis-(3-aminophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (40)
Mp181-183℃;EIMS m/z301[M
+];IR(KBr)cm
-1:2766(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:3.16(s,2H),3.31(s,3H),3.67(s,1H),4.45~4.54(m,4H),7.02~7.11(m,4H),7.28~7.36(m,2H),7.46~7.52(m,2H),8.22(s,1H),10.21(s,1H)。
3,3-bis-(4-aminomethyl phenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (41)
Mp165-167℃;EIMS m/z299[M
+];IR(KBr)cm
-1:2764(OH),3027(NH);
1H NMR(DMSO-d
6)δppm:2.47(s,6H),3.18(s,2H),3.29(s,3H),3.69(s,1H),6.92(dd,4H),7.39(dd,4H),8.26(s,1H),10.23(s,1H)。
3,3-bis-(3-Methylaminophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (42)
Mp186-188℃;EIMS m/z:357[M
+];IR(KBr)cm
-1:2761(OH),3026(NH);
1H NMR(DMSO-d
6)δppm:3.16(s,2H),3.26(s,3H),3.37(s,12H),3.65(s,1H),6.87(dd,4H),7.27(dd,4H),8.24(s,1H),10.23(s,1H)。
3-phenyl-3-(2-hydroxyl-3-octyloxyphenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (43)
Mp160-162℃;EIMS m/z:415[M
+];IR(KBr)cm
-1:2767(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:1.35~1.44(m,15H),3.16(s,2H),3.31(s,3H),3.67(s,1H),4.12(t,2H),5.79(s,1H),6.73(dd,2H),7.18(d,1H),7.46~7.50(m,3H),7.52~7.58(m,2H),8.24(s,1H),10.23(s,1H)。
3-phenyl-3-(3,4-3,5-dimethylphenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (44)
Mp147-149℃;EIMS m/z:299[M
+];IR(KBr)cm
-1:2762(OH),3027(NH);
1H NMR(DMSO-d
6)δppm:2.75(s,6H),3.19(s,2H),3.29(s,3H),3.64(s,1H),7.13(d,2H),7.29(d,1H),7.46~7.51(m,3H),7.54~7.63(m,2H),8.24(s,1H),10.21(s,1H)。
3-phenyl-3-(2-hydroxyl-4-p-methoxy-phenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (45)
Mp127-129℃;EIMS m/z:317[M
+];IR(KBr)cm
-1:2762(OH),3022(NH);
1H NMR(DMSO-d
6)δppm:3.18(s,2H),3.29(s,3H),3.69(s,1H),4.13(s,3H),5.74(s,1H),6.77(d,2H),7.18(d,1H),7.46~7.52(m,3H),7.57~7.64(m,2H),8.24(s,1H),10.23(s,1H)。
3-(2-fluorophenyl)-3-(3-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (46)
Mp134-136℃;EIMS m/z:307[M
+];IR(KBr)cm
-1:2762(OH),3023(NH);
1H NMR(DMSO-d
6)δppm:3.16(s,2H),3.31(s,3H),3.67(s,1H),7.09(d,1H),7.24(m,2H),7.34~7.43(m,1H),7.46~7.50(m,2H),7.76(dd,1H),7.81~7.89(m,1H),8.21(s,1H),10.20(s,1H)。
3-phenyl-3-(2,4 difluorobenzene base)-3-hydroxyl propionyl-N-methyl hydroxamic acid (47)
Mp149-151℃;EIMS m/z:307[M
+];IR(KBr)cm
-1:2761(OH),3025(NH);
1H NMR(DMSO-d
6)δppm:3.16(s,2H),3.32(s,3H),3.67(s,1H),6.91(d,1H),7.14(dd,1H),7.45(dd,1H),7.46~7.53(m,3H),7.56~7.65(m,2H),8.24(s,1H),10.25(s,1H)。
3-phenyl-3-(3,4-difluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (48)
Mp134-136℃;EIMS m/z:307[M
+];IR(KBr)cm
-1:2762(OH),3023(NH);
1H NMR(DMSO-d
6)δppm:3.16(s,2H),3.26(s,3H),3.67(s,1H),7.13(d,1H),7.21(dd,1H),7.27(d,1H),7.46~7.53(m,3H),7.56~7.65(m,2H),8.24(s,1H),10.20(s,1H)。
3-(3-hydroxy phenyl)-3-(2,3,4-trihydroxy-phenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (49)
Mp170-172℃;EIMS m/z335[M
+];IR(KBr)cm
-1:2764(OH),3020(NH);
1H NMR(DMSO-d
6)δppm:3.18(s,2H),3.29(s,3H),3.69(s,1H),5.78(s,4H),6.84(d,1H),7.01(d,1H),7.25(dd,1H),7.33~7.41(m,3H),8.26(s,1H),10.31(s,1H)。
3-phenyl-3-(2,4-dihydroxy phenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (50)
Mp170-172℃;EIMS m/z:335[M
+];IR(KBr)cm
-1:2768(OH),3021(NH);
1H NMR(DMSO-d
6)δppm:3.16(s,2H),3.29(s,3H),3.29(s,3H),3.67(s,1H),5.76(s,4H),6.85(d,1H),7.01(d,1H),7.26(dd,1H),7.33(m,3H),8.21(s,1H),10.32(s,1H)。
3-phenyl-3-(2-chloro-4 nitrophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (51)
Mp193-194℃;EIMS m/z350[M
+];IR(KBr)cm
-1:2762(OH),3025(NH);
1H NMR(DMSO-d
6)δppm:3.17(s,2H),3.33(s,3H),3.67(s,1H),5.79(s,2H),7.46~7.52(m,3H),7.76(d,1H),8.12(dd,1H),8.24(s,1H),8.31(d,1H),10.19(s,1H)。
3-phenyl-3-(4-aminomethyl phenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (52)
Mp148-149℃;EIMS m/z285[M
+];IR(KBr)cm
-1:2763(OH),3021(NH);
1H NMR(DMSO-d
6)δppm:2.37(s,3H),3.17(s,2H),3.26(s,3H),3.67(s,1H),5.72(s,2H),6.92(dd,1H),7.30(dd,2H),7.46~7.56(m,3H),7.70(d,1H),8.20(s,1H),10.18(s,1H)。
3-phenyl-3-(2-amino-4-nitrophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (53)
Mp122-124℃;EIMS m/z331[M
+];IR(KBr)cm
-1:2767(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:3.17(s,2H),3.32(s,3H),3.67(s,1H),6.59(s,2H),7.40~7.47(m,3H),7.49~7.56(dd,1H),7.56~7.61(m,2H),7.63~7.74(d,1H),7.73(d,1H),8.24(s,1H),10.14(s,1H)。
3-phenyl-3-(2-amino-4-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (54)
Mp147-149℃;EIMS m/z320[M
+];IR(KBr)cm
-1:2765(OH),3020(NH);
1H NMR(DMSO-d
6)δppm:3.19(s,2H),3.29(s,3H),3.65(s,1H),6.58(s,2H),6.83(d,1H),7.14(d,1H),7.38~7.46(m,3H),7.51~7.62(m,2H),7.94(dd,1H),8.20(s,1H),10.19(s,1H)。
3-(2-hydroxy phenyl)-3-(2-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (55)
Mp186-188℃;EIMS m/z305[M
+];IR(KBr)cm
-1:2766(OH),3023(NH);
1H NMR(DMSO-d
6)δppm:3.17(s,2H),3.27(s,3H),3.67(s,1H),5.76(s,1H),7.14(dd,1H),7.27(dd,1H),7.43~7.56(m,4H),7.73(d,1H),7.90~7.97(m,1H),8.22(s,1H),10.21(s,1H)。
3-(2-hydroxy phenyl)-3-(2-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (56)
Mp204-206℃;EIMS m/z:321[M
+];IR(KBr)cm
-1:2763(OH),3021(NH);
1H NMR(DMSO-d
6)δppm:3.18(s,2H),3.29(s,3H),3.64(s,1H),5.78(s,1H),7.03-7.13(m,1H),7.14(dd,1H),7.24~7.33(m,1H),7.37~7.42(m,2H),7.47~7.55(m,2H),7.87(dd,1H),8.24(s,1H),10.16(s,1H)。
3-(2-hydroxy phenyl)-3-(2-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (57)
Mp217-219℃;EIMS m/z365[M
+];IR(KBr)cm
-1:2765(OH),3021(NH);
1H NMR(DMSO-d
6)δppm:3.18(s,2H),3.29(s,3H),3.64(s,1H),5.78(s,1H),7.03-7.13(m,1H),7.14(dd,1H),7.24~7.32(m,1H),7.35~7.42(m,2H),7.49~7.53(m,2H),7.91(dd,1H),8.27(s,1H),10.18(s,1H)。
3-(2-aminophenyl)-3-(2-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (58)
Mp194-196℃;EIMS m/z304[M
+];IR(KBr)cm
-1:2760(OH),3027(NH);
1H NMR(DMSO-d
6)δppm:3.15(s,2H),3.27(s,3H),3.67(s,1H),6.58(s,2H),7.15~7.20(m,2H),7.24~7.33(m,3H),7.47(dd,1H),7.66(dd,1H),7.89~7.92(m,1H),8.22(s,1H),10.17(s,1H)。
3-(2-aminophenyl)-3-(2-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (59)
Mp180-182℃;EIMS m/z320[M
+];IR(KBr)cm
-1:2764(OH),3023(NH);
1H NMR(DMSO-d
6)δppm:3.15(s,2H),3.32(s,3H),3.67(s,1H),6.59(s,2H),7.15~7.23(m,2H),7.24~7.33(m,2H),7.35~7.41(m,2H),7.46(dd,1H),7.82(dd,1H),8.22(s,1H),10.18(s,1H)。
3-(2-aminophenyl)-3-(2-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (60)
Mp217-219℃;EIMS m/z364[M
+];IR(KBr)cm
-1:2765(OH),3021(NH);
1H NMR(DMSO-d
6)δppm:3.18(s,2H),3.29(s,3H),3.69(s,1H),6.56(s,2H),7.15~7.23(m,2H),7.24~7.31(m,2H),7.38~7.40(m,2H),7.51~7.57(m,1H),7.76(dd,1H),8.20(s,1H),10.19(s,1H)。
3-(2-nitrophenyl)-3-(2-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (61)
Mp198-200℃;EIMS m/z:334[M
+];IR(KBr)cm
-1:2762(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:3.15(s,2H),3.33(s,3H),3.67(s,1H),7.27~7.35(m,1H),7.46(dd,1H),7.77(dd,2H),7.86~7.92(m,2H),7.95~8.02(m,1H),8.11(dd,1H),8.24(s,1H),10.18(s,1H)。
3-(2-nitrophenyl)-3-(2-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (62)
Mp209-211℃;EIMS m/z:350[M
+];IR(KBr)cm
-1:2764(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:3.18(s,2H),3.29(s,3H),3.69(s,1H),7.31~7.39(m,2H),7.44(dd,1H),7.72(dd,2H),7.86~7.94(m,1H),7.95~7.99(m,1H),8.15(dd,1H),8.20(s,1H),10.22(s,1H)。
3-(2-nitrophenyl)-3-(2-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (63)
Mp219-221℃;EIMS m/z:394[M
+];IR(KBr)cm
-1:2767(OH),3022(NH);
1H NMR(DMSO-d
6)δppm:3.15(s,2H),3.29(s,3H),3.69(s,1H),7.37~7.41(m,2H),7.48~7.56(m,1H),7.65(dd,1H),7.70~7.79(m,1H),7.86~7.92(m,1H),7.95~8.05(m,1H),8.11(dd,1H),8.23(s,1H),10.16(s,1H)。
3-(2-p-methoxy-phenyl)-3-(2-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (64)
Mp208-209℃;EIMS m/z:319[M+];IR(KBr)cm-1:2762(OH),3025(NH);1H NMR(DMSO-d6)δppm:3.12(s,2H),3.33(s,3H),3.67(s,1H),4.24(s,3H),7.17~7.21(m,3H),7.29~7.38(m,1H),7.37(dd,1H),7.46~7.56(dd,1H),7.70(dd,1H),7.83~7.94(m,1H),8.20(s,1H),10.18(s,1H)。
3-(2-p-methoxy-phenyl)-3-(2-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (65)
Mp202-204℃;EIMS m/z:335[M
+];IR(KBr)cm
-1:2762(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:3.12(s,2H),3.28(s,3H),3.67(s,1H),4.29(s,3H),7.17~7.22(m,3H),7.41~7.46(m,4H),7.87(dd,1H),8.20(s,1H),10.20(s,1H)。
3-(2-p-methoxy-phenyl)-3-(2-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (66)
Mp231-233℃;EIMS m/z:379[M
+];IR(KBr)cm
-1:2762(OH),3020(NH);
1H NMR(DMSO-d
6)δppm:3.14(s,2H),3.29(s,3H),3.67(s,1H),4.29(s,3H),7.17~7.22(m,3H),7.38(dd,2H),7.51~7.64(m,2H),7.67(dd,1H),8.20(s,1H),10.21(s,1H)。
3-(2-ethoxyl phenenyl)-3-(2-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (67)
Mp218-219℃;EIMS m/z:333[M
+];IR(KBr)cm
-1:2765(OH),3026(NH);
1H NMR(DMSO-d
6)δppm:2.35(t,3H),3.10(s,2H),3.29(s,3H),3.69(s,1H),4.27~4.31(m,2H),7.17~7.24(m,3H),7.27~7.35(m,1H),7.38(dd,1H),7.46(dd,1H)7.69(dd,1H),7.82~7.87(m,1H),8.23(s,1H),10.14(s,1H)。
3-(2-ethoxyl phenenyl)-3-(2-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (68)
Mp206-208℃;EIMS m/z:349[M
+];IR(KBr)cm
-1:2761(OH),3027(NH);
1H NMR(DMSO-d
6)δppm:2.38(t,3H),3.14(s,2H),3.29(s,3H),3.67(s,1H),4.27~4.31(m,2H),7.17~7.25(m,3H),7.27~7.30(m,1H),7.51~7.59(m,3H)7.87(dd,1H),8.20(s,1H),10.22(s,1H)。
3-(2-ethoxyl phenenyl)-3-(2-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (69)
Mp227-229℃;EIMS m/z:393[M
+];IR(KBr)cm
-1:2763(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:2.38(t,3H),3.10(s,2H),3.26(s,3H),3.67(s,1H),4.27~4.31(m,2H),7.17~7.27(m,3H),7.27~7.32(m,1H),7.49~7.53(m,3H)7.63(dd,1H),8.20(s,1H),10.19(s,1H)。
3-(2-hydroxy phenyl)-3-(3-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (70)
Mp212-214℃;EIMS m/z:321[M
+];IR(KBr)cm
-1:2764(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:3.10(s,2H),3.28(s,3H),3.67(s,1H),5.69(s,1H),6.92~7.04(m,2H),7.33~7.39(m,2H),7.47~7.55(m,2H),7.58~7.64(m,1H),7.79(dd,1H),8.22(s,1H),10.16(s,1H)。
3-(2-hydroxy phenyl)-3-(3-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (71)
Mp175-177℃;EIMS m/z:365[M
+];IR(KBr)cm
-1:2768(OH),3026(NH);
1H NMR(DMSO-d
6)δppm:3.10(s,2H),3.29(s,3H),3.69(s,1H),5.69(s,1H),6.92~7.02(m,2H),7.37~7.45(m,3H),7.49~7.55(m,1H),7.69(dd,2H),8.20(s,1H),10.23(s,1H)。
3-(2-hydroxy phenyl)-3-(3-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (72)
Mp205-207℃;EIMS m/z:305[M
+];IR(KBr)cm
-1:2765(OH),3027(NH);
1H NMR(DMSO-d
6)δppm:3.10(s,2H),3.29(s,3H),3.69(s,1H),5.69(s,1H),6.92~7.04(m,3H),7.37~7.41(m,4H),7.50~7.58(m,1H),8.20(s,1H),10.19(s,1H)。3-(2-aminophenyl)-3-(3-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (73)
Mp169-171℃;EIMS m/z:320[M
+];IR(KBr)cm
-1:2764(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:3.17(s,2H),3.29(s,3H),3.67(s,1H),6.57(s,2H),6.97~7.05(m,2H),7.28~7.32(m,2H),7.48~7.56(m,2H),7.55~7.60(m,2H),8.22(s,1H),10.18(s,1H)。
3-(2-aminophenyl)-3-(3-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (74)
Mp215-217℃;EIMS m/z:365[M
+];IR(KBr)cm
-1:2760(OH),3026(NH);
1H NMR(DMSO-d
6)δppm:3.11(s,2H),3.29(s,3H),3.69(s,1H),6.55(s,2H),6.98~7.05(m,2H),7.28~7.35(m,2H),7.39~7.43(m,1H),7.51~7.57(m,1H),7.69~7.74(m,2H),8.20(s,1H),10.19(s,1H)。
3-(2-aminophenyl)-3-(3-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (75)
Mp161-163℃;EIMS m/z:304[M
+];IR(KBr)cm
-1:2766(OH),3023(NH);
1H NMR(DMSO-d
6)δppm:3.12(s,2H),3.31(s,3H),3.66(s,1H),6.54(s,2H),6.95~7.02(m,3H),7.29~7.37(m,3H),7.35~7.40(m,1H),7.43~7.54(m,1H),8.22(s,1H),10.22(s,1H)。
3-(2-nitrophenyl)-3-(3-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (76)
Mp206-208℃;EIMS m/z:350[M
+];IR(KBr)cm
-1:2760(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:3.16(s,2H),3.29(s,3H),3.66(s,1H),7.45~7.53(m,2H),7.58~7.63(m,2H),7.86~7.94(m,3H),7.97~8.06(dd,1H),8.22(s,1H),10.15(s,1H)。
3-(2-nitrophenyl)-3-(3-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (77)
Mp219-221℃;EIMS m/z:394[M
+];IR(KBr)cm
-1:2762(OH),3020(NH);
1H NMR(DMSO-d
6)δppm:3.15(s,2H),3.29(s,3H),3.69(s,1H),7.37(dd,1H),7.46(dd,1H),7.53(m,2H),7.86~796(m,3H),7.97(dd,1H),8.23(s,1H),10.18(s,1H)。
3-(2-nitrophenyl)-3-(3-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (78)
Mp166-168℃;EIMS m/z:334[M
+];IR(KBr)cm
-1:2762(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:3.15(s,2H),3.30(s,3H),3.62(s,1H),7.13(dd,1H),7.22~7.33(m,1H),7.33~7.40(m,1H),7.43~7.49(m,1H),7.86~7.91(m,3H),7.97(dd,1H),8.23(s,1H),10.19(s,1H)。
3-(2-p-methoxy-phenyl)-3-(3-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (79)
Mp148-149℃;EIMS m/z:335[M
+];IR(KBr)cm
-1:2763(OH),3026(NH);
1H NMR(DMSO-d
6)δppm:3.14~3.26(m,5H),3.29(s,3H),3.68(s,1H),6.99~7.05(m,3H),7.37~7.42(m,1H),7.43~7.49(m,2H),7.55(dd,2H),8.23(s,1H),10.15(s,1H)。
3-(2-p-methoxy-phenyl)-3-(3-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (80)
Mp154-156℃;EIMS m/z:379[M
+];IR(KBr)cm
-1:2764(OH),3022(NH);
1H NMR(DMSO-d
6)δppm:3.13(m,5H),3.32(s,3H),3.65(s,1H),6.97-7.06(m,3H),7.39~7.44(m,2H),7.53~7.62(m,1H),7.64~7.71(m,2H),8.23(s,1H),10.23(s,1H)。
3-(2-p-methoxy-phenyl)-3-(3-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (81)
Mp134-136℃;EIMS m/z:319[M
+];IR(KBr)cm
-1:2763(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:3.14~3.20(m,5H),3.27(s,3H),3.62(s,1H),7.05~7.15(m,4H),7.25(dd,1H),7.37~7.46(m,2H),7.47~7.53(m,1H),8.22(s,1H),10.21(s,1H)。
3-(2-ethoxyl phenenyl)-3-(3-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (82)
Mp195-197℃;EIMS m/z:349[M
+];IR(KBr)cm
-1:2763(OH),3021(NH);
1H NMR(DMSO-d
6)δppm:2.03~2.12(m,3H),3.14~3.21(m,4H),3.27(s,3H),3.61(s,1H),7.00~7.16(m,3H),7.37(dd,1H),7.46~7.53(m,2H),7.54~7.60(m,1H),7.63~7.69(m,1H),8.20(s,1H),10.22(s,1H)。
3-(2-ethoxyl phenenyl)-3-(3-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (83)
Mp197-199℃;EIMS m/z:393[M
+];IR(KBr)cm
-1:2761(OH),3025(NH);
1H NMR(DMSO-d
6)δppm:2.04~2.10(m,3H),3.17~3.25(m,4H),3.29(s,3H),3.61(s,1H),7.00~7.10(m,3H),7.38~7.42(m,2H),7.47~7.56(m,1H),7.67~7.72(m,2H),8.20(s,1H),10.24(s,1H)。
3-(3-ethoxyl phenenyl)-3-(3-fluorophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (84)
Mp179-17981℃;EIMS m/z:333[M
+];IR(KBr)cm
-1:2761(OH),3027(NH);
1H NMR(DMSO-d
6)δppm:2.03~2.12(m,3H),3.12~3.25(m,4H),3.27(s,3H),3.61(s,1H),6.93~7.08(m,3H),7.22~7.33(m,2H),7.39~7.43(m,2H),7.49~7.55(m,1H),8.20(s,1H),10.19(s,1H)。
3-(3-ethoxyl phenenyl)-3-(3-chloro-phenyl-)-3-hydroxyl propionyl-N-methyl hydroxamic acid (85)
Mp186-188℃;EIMS m/z:349[M
+];IR(KBr)cm
-1:2760(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:2.13-2.22(m,3H),3.17~3.22(m,4H),3.29(s,3H),3.65(s,1H),6.93~7.05(m,2H),7.20~7.25(m,1H),7.38~7.47(m,2H),7.49~7.53(m,1H),7.57~7.63(m,2H),8.23(s,1H),10.22(s,1H)。
3-(3-ethoxyl phenenyl)-3-(3-bromophenyl)-3-hydroxyl propionyl-N-methyl hydroxamic acid (86)
Mp219-221℃;EIMS m/z:393[M
+];IR(KBr)cm
-1:2763(OH),3024(NH);
1H NMR(DMSO-d
6)δppm:2.12~2.22(m,3H),3.17~3.24(m,4H),3.31(s,3H),3.63(s,1H),6.97~7.08(m,2H),7.20~7.32(m,1H),7.35~7.39(m,2H),7.45~7.54(m,1H),7.66~7.72(m,2H),8.26(s,1H),10.23(s,1H)。