Additional file 1
Solvent effects on the structure-property relationship of anticonvulsant
hydantoin derivatives. A solvatochromic analysis.
Nemanja Trišović, Nataša Valentić*, Gordana Ušćumlić
Department of Organic Chemistry, Faculty of Technology and Metallurgy, University of
Belgrade, Karnegijeva 4, 11000 Belgrade, Serbia
*
Corresponding author:
Tel.: +381 11 3303671
fax: +381 11 3370387
E-mail address: NT: n.trisovic@yahoo.com
NV: naca@tmf.bg.ac.rs
GU: goca@tmf.bg.ac.rs
1
General Procedure for the Preparation of 5-alkyl-5-phenylhydantoins [1].
Following the method of Bucherer and Lieb, the appropriate ketone (0.020 mol) was
dissolved in 50 % ethanol (50 ml) and ammonium carbonate (7.70 g, 0.080 mol) and
potassium cyanide (2.60 g, 0.040 mol) were then added. This mixture was warmed under
a condenser at temperature of 60 °C for 15 h, after which the solution was concentrated to
approximately two-thirds of the initial volume, chilled in an ice-bath and filtered. The
product was dissolved in 5 % sodium hydroxide solution, filtered from unreacted ketone
and reprecipitated by acidification with hydrochloric acid. Recrystallization from 60 %
ethanol yielded a crystalline product.
5-Ethyl-5-phenylhydantoin (C11H12N2O2). White crystalline solid; m.p.: 196-199 °C (lit.
m.p.: 194-196 [2]); yield 72 %; (KBr, cm-1): ν 3286 (NH), 3214 (NH), 1771 (C=O), 1714
(C=O); 1H NMR (200 MHz, DMSO-d6): δ 10.74 (s, 1H, N(3)H), 8.66 (s, 1H, N(1)H),
7.53–7.27 (m, 5H, Ph-H), 2.16–1.80 (m, 2H, CH2), 0.81 (t, J = 7.2 Hz, 3H, CH3);
13
C
NMR (50 MHz, DMSO-d6): δ 176.6 (C4), 157.0 (C2), 139.4, 128.7, 128.0, 125.7, 68.3
(C5), 31.4, 8.3.
5-Methyl-5-phenylhydantoin (C10H10N2O2). White crystalline solid; m.p.: 194-196 °C (lit.
m.p.: 196-198 [2]); yield 75 %; IR (KBr, cm-1): ν 3283 (NH), 3206 (NH), 1770 (C=O),
1717 (C=O); 1H NMR (200 MHz, DMSO-d6): δ 10.77 (s, 1H, N(3)H), 8.64 (s, 1H,
N(1)H), 7.51–7.28 (m, 5H, Ph-H), 1.66 (s, 3H, Me);
13
C NMR (50 MHz, DMSO-d6): δ
177.4 (C4), 156.6 (C2), 140.2, 128.8, 128.1, 125.6, 64.2 (C5), 25.2.
General Procedure for the Preparation of Compounds 1–7 and 11–25 [3].
The appropriate 5-substituted-5-phenylhydantoin (0.010 mol) was dissolved in 60 ml of
dimethylformamide and potassium carbonate (5.60 g, 0.041 mol) was added. Alkyl halide
(methyl iodide, ethyl bromide, n-propyl bromide, isopropyl bromide, allyl bromide, nbutyl chloride, isobutyl bromide or benzyl bromide, 0.011 eq) was then added and the
reaction was stirred over the night. The reaction mixture was poured into three volumes
2
of water and extracted with ethyl acetate. The ethyl acetate extracts were washed with 5%
sodium hydroxide solution, water, and brine, and then dried over magnesium sulfate. The
solvent was removed under reduced pressure and the resulting solid was recrystallized
from ethanol.
3-Methyl-5,5-diphenylhydantoin (1, C16H14N2O2). White crystalline solid; m.p.: 211–213
°C (lit. m.p.: 213–214 °C [4]); yield: 68 %; IR (KBr, cm-1): ν 3286 (NH), 1773 (C=O),
1701 (C=O); 1H NMR (200 MHz, DMSO-d6): δ 9.65 (s, 1H, NH), 7.38–7.26 (m, 10H,
Ph-H), 2.94 (s, 3H, CH3);
13
C NMR (50 MHz, DMSO-d6): δ 173.6 (C4), 155.8 (C2),
139.9, 128.8, 128.4, 128.3, 127.4, 126.9, 69.5 (C5), 4.7.
3-Ethyl-5,5-diphenylhydantoin (2, C17H16N2O2). White crystalline solid; m.p.: 152–154
°C (lit. m.p.: 156 °C [4]); yield: 42 %; (KBr, cm-1): ν 3281 (NH), 1774 (C=O), 1696
(C=O); 1H NMR (200 MHz, DMSO-d6) δ 9.65 (s, 1H, NH), 7.44–7.26 (m, 10H, Ph-H),
3.48 (q, J = 7.1 Hz, 2H, CH2), 1.10 (t, J = 7.0 Hz, 3H, CH3); 13C NMR (50 MHz, DMSOd6): δ 173.3 (C4), 155.5 (C2), 140.0, 128.8, 128.9, 128.4, 128.1, 126.9, 69.2 (C5), 33.3,
13.5.
3-n-Propyl-5,5-diphenylhydantoin (3, C18H18N2O2). White crystalline solid; m.p.: 143–
145 °C (lit. m.p.: 144–147 °C [5]); yield: 71 %; IR (KBr, cm-1): ν 3170 (NH), 1772
(C=O), 1708 (C=O); 1H NMR (200 MHz, DMSO-d6): δ 9.65 (s, 1H, NH), 7.50–7.26 (m,
10H, Ph-H), 3.45–3.38 (m, 2H, CH2CH2CH3), 1.64–1.45 (m, 2H, CH2CH2CH3), 0.78 (t, J
= 7.3 Hz, 3H, CH3) ppm; 13C NMR (50 MHz, DMSO-d6): 173.3 (C4), 155.4 (C2), 140.1,
128.8, 126.3, 126.8, 68.4 (C5), 43.1, 19.6.
3-Isopropyl-5,5-diphenylhydantoin (4, C18H18N2O2). White crystalline solid; m.p.: 180–
185 °C; yield: 54 %; IR (KBr, cm-1): ν 3209 (NH), 1772 (C=O), 1708 (C=O); 1H NMR
(200 MHz, DMSO-d6): δ 9.59 (s, 1H, NH), 7.77–7.30 (m, 10H, Ph-H), 4.31–4.18 (m, 1H,
CH(CH3)2), 1.33 (d, J = 6.8 Hz, 6H, CH(CH3)2); 13C NMR (50 MHz, DMSO-d6): δ 173.3
(C4), 155.4 (C2), 140.1, 128.8, 126.3, 126.8, 68.4 (C5), 43.1, 19.6.
3
3-Allyl-5,5-diphenylhydantoin (5, C18H16N2O2). White crystalline solid; m.p.: 114–117
°C; yield: 68 %; IR (KBr, cm-1): ν 3274 (NH), 1770 (C=O), 1704 (C=O); 1H NMR (200
MHz, DMSO-d6): δ 9.73 (s, 1H, NH), 7.39–7.22 (m, 10H, Ph-H), 5.91–5.72 (m, 1H,
CH2CH=CH2), 5.08 (d, J = 10 Hz, 1H, CH2CH=CH2), 4.98 (d, J = 17 Hz, 1H,
CH2CH=CH2), 4.06 (d, J = 5 Hz, 2H, CH2CH=CH2); 13C NMR (50 MHz, DMSO-d6): δ
173.1 (C4), 155.2 (C2), 139.9, 132.3, 128.8, 128.4, 126.9, 116.5, 69.4 (C5), 40.2.
3-n-Butyl-5,5-diphenylhydantoin (6, C19H20N2O2). White crystalline solid; m.p.: 134–136
°C (lit. m.p.: 135–137 °C [6]); yield: 62 %; IR (KBr, cm-1): ν 3171 (NH), 1770 (C=O),
1705 (C=O); 1H NMR (200 MHz, DMSO-d6): δ 9.64 (s, 1H, NH), 7.44–7.25 (m, 10H,
Ph-H), 3.45 (t, J = 6.7 Hz, 2H, CH2CH2CH2CH3), 1.58– 1.44 (m, 2H, CH2CH2CH2CH3),
1.30–1.11 (m, 2H, CH2CH2CH2CH3), 0.84 (t, J = 7.0 Hz, 3H, CH3); 13C NMR (50 MHz,
DMSO-d6): δ 173.6 (C4), 155.8 (C2), 140.0, 128.4, 126.8, 69.2 (C5), 45.4, 27.1, 19.9.
3-Isobutyl-5,5-diphenylhydantoin (7, C19H20N2O2). White crystalline solid; m.p.: 119–
122 °C; yield: 67 %; IR (KBr, cm-1): ν 3293 (NH), 1705 (C=O), 1775 (C=O); 1H NMR
(200 MHz, DMSO-d6): δ 9.66 (s, 1H, NH), 7.44–7.26 (m, 10H, Ph–H), 3.29–3.25 (m, 2H,
CH2CH(CH3)2), 2.03–1.89 (m, 1H, CH2CH(CH3)2), 0.78 (d, J = 7.0 Hz, 6H, CH3);
13
C
NMR (50 MHz, DMSO-d6): δ 173.6 (C4), 155.8 (C2), 140.0, 128.8, 128.3, 126.8, 69.2
(C5), 45.4, 27.1, 19.9.
3-Benzyl-5,5-diphenylhydantoin (11, C22H18N2O2). White crystalline solid; m.p.: 144–146
°C (lit. m.p.: 145–146 °C [4]); yield: 49 %; IR (KBr, cm-1): ν 3275 (NH), 1760 (C=O),
1715 (C=O); 1H NMR (200 MHz, DMSO-d6): δ 9.82 (s, 1H, NH), 7.44–7.22 (m, 15H,
Ph-H), 4.65 (s, 2H, CH2-N);
13
C NMR (50 MHz, DMSO-d6): δ 173.3 (C4), 155.5 (C2),
139.8, 136.8, 128.8, 128.8, 128.5, 128.3, 127.8, 127.5, 126.8, 69.5 (C5), 41.7.
3-Methyl-5-ethyl-5-phenylhydantoin (12, C12H14N2O2). White crystalline solid; m.p.:
134–136 °C (lit. m.p.: 136–137 °C [7]); yield: 74 %; IR (KBr, cm-1): ν 3283 (NH), 1772
(C=O), 1698 (C=O); 1H NMR (200 MHz, DMSO-d6): δ 8.98 (s, 1H, N-H), 7.55–7.28 (m,
5H, Ph-H), 3.38 (s, 3H, NCH3), 2.18–1.89 (m, 2H, CH2CH3), 0,74 (t. J = 7.4 Hz, 3H,
4
CH2CH3); 13C NMR (50 MHz, DMSO-d6): 174.0 (C4), 156.4 (C2), 139.9, 129.3, 128.7,
126.4, 70.5 (C5), 40.5, 31.5, 7.6.
3,5-Diethyl-5-phenylhydantoin (13, C13H16N2O2). White crystalline solid; m.p.: 86–88 °C
(lit. m.p.: 88–89 °C [4]); yield: 56 %; IR (KBr, cm-1): ν 3291 (NH), 1773 (C=O), 1699
(C=O); 1H NMR (200 MHz, DMSO-d6): δ 8.95 (s, 1H, NH), 7.55-7.29 (m, 5H, Ph-H),
3.45–3.42 (m, 2H, NCH2CH3), 2.21–1.84 (m, 2H, CCH2CH3), 1.05 (t, J = 7.3 Hz, 3H,
NCH2CH3), 0.80 (t, J = 7.3 Hz, 3H, CCH2CH3); 13C NMR (50 MHz, DMSO-d6): δ 174.7
(C4), 156.2 (C2), 139.1, 128.8, 128.1, 125.7, 66.9 (C5), 33.0, 31.5, 13.4, 8.1.
3-n-Propyl-5-ethyl-5-phenylhydantoin (14, C14H18N2O2). White crystalline solid; m.p.:
83–85 °C (lit. m.p.: 84–86 °C [7]); yield:: 66 %; IR (KBr, cm-1): ν 3222 (NH), 1763
(C=O), 1703 (C=O); 1H NMR (200 MHz, DMSO-d6): δ 8.96 (s, 1H, N-H), 7.54–7.28 (m,
5H, Ph-H), 3.33 (t, Ј = 7.0 Hz, 2H, CH2CH2CH3), 2.21–1.85 (m, 2H, CCH2CH3), 1.59–
1.41 (m, 2H, CH2CH2CH3), 0.80 (t, J = 7.4 Hz, 3H, CH3), 0.77 (t, J = 7.2 Hz, 3H, CH3) –
signal at 0.80 is partly covered with signal at 0.77;
13
C NMR (50 MHz, DMSO-d6): δ
174.3 (C4), 156.4 (C2), 139.2, 128.8, 128.1, 125.7, 66.9 (C5), 39.6, 31.4, 21.1, 11.1, 8.2.
3-Isopropyl-5-ethyl-5-phenylhydantoin (15, C14H18N2O2). White crystalline solid; m.p.:
96–98 °C; yield: 48 %; IR (KBr, cm-1): ν 3241 (NH), 1766 (C=O), 1708 (C=O); 1H NMR
(200 MHz, DMSO-d6): δ 8.89 (s, 1H, NH), 7.53–7.28 (m, 5H, Ph-H), 4.24–4.10 (m, 1H,
CH(CH3)2), 2.21–1.81 (m, 2H, CCH2CH3), 1.29 (t, J = 6,4 Hz, 6H, CH(CH3)2), 0.80 (t, J
= 7,3 Hz, 3H, CCH2CH3); 13C NMR (50 MHz, DMSO-d6): δ 174.7 (C5), 156.2 (C2),
139.3, 128.7, 128.1, 125.7, 66.1 (C5), 42.8, 31.5, 19.6, 19.5, 8.0.
3-Allyl-5-ethyl-5-phenylhydantoin (16, C14H68N2O2). White crystalline solid; m.p.: 87–89
°C (lit. m.p.: 88–90 °C [7]); yield: 73 %; IR (KBr, cm-1): ν 3282 (NH), 1775 (C=O), 1707
(C=O); 1H NMR (200 MHz, DMSO-d6): δ 9.04 (s, 1H, NH), 7.56–7.29 (m, 5H, Ph-H),
5.86–5.67 (m, 1H, CH2CH=CH2), 5.09-4.94 (m, 2H, CH2CH=CH2), 3.97 (d, J = 5.0 Hz,
2H, CH2CH=CH2), 2.22–1.87 (m, 2H, CCH2CH3), 0.81 (t, J = 7.3 Hz, 3H, CCH2CH3);
5
C NMR (50 MHz, DMSO-d6): δ 174.5 (C4), 155.9 (C2), 132.4, 128.8, 128.2, 125.7,
13
116.5, 67.2 (C5), 49.9, 31.4, 8.2.
3-n-Butyl-5-ethyl-5-phenylhydantoin (17, C15H20N2O2). White crystalline solid; m.p.: 70–
72 °C (lit. m.p.: 72–73 °C [7]); yield: 57 %; IR (KBr, cm-1): ν 3259 (NH), 1779 (C=O),
1704 (C=O); 1H NMR (200 MHz, DMSO-d6): δ 8.95 (s, 1H, NH), 7.54–7.28 (m, 5H, PhH), 3.36 (t, J = 6.2 Hz, 2H, CH2CH2CH2CH3), 2.21–1.84 (m, 2H, CCH2CH3), 1.53–1.39
(m, 2H, CH2CH2CH2CH3), 1.29–1.11 (2H, m, CH2CH2CH2CH3), 0.84 (t, J = 7.2 Hz, 3H,
CH2CH2CH2CH3), 0.80 (t, J = 7.0 Hz, 3H, CCH2CH3) – signal at 0.84 is partly covered
with signal at 0.80;
13
C NMR (50 MHz, DMSO-d6): δ 174.9 (C4), 156.4 (C2), 139.1,
128.2, 128.1, 125,.7, 66.9 (C5), 37.6, 31.4, 29.8, 19.4, 13.6, 8.1.
3-Isobutyl-5-ethyl-5-phenylhydantoin (18, C15H20N2O2). White crystalline solid; m.p.:
110–112 °C; yield: 43 %; IR (KBr, cm-1): ν 3283 (NH), 1772 (C=O), 1698 (C=O) cm-1;
1
H NMR (200 MHz, DMSO-d6): 8.97 (s, 1H, NH), 7.55–7.28 (m, 5H, Ph-H), 3.20–3.16
(d, J = 6,8 Hz, 2H, CH2CH2(CH3)2), 2.17–1.84 (m, 2H, CCH2CH3), 0.85–0.75 (m, 9H,
CH3);
13
C NMR (50 MHz, DMSO-d6): δ 175.1 (C5), 156.5 (C2), 139.2, 128.7, 128.1,
125.6, 66.9 (C5), 45.2, 31.3, 27.1, 19.9, 8.2.
3-Benzyl-5-ethyl-5-phenylhydantoin (19, C18H18N2O2). White crystalline solid; m.p.:
138–140 °C (lit. m.p.:139–140 °C [7]); yield: 62 %; IR (KBr, cm-1): ν 3211 (NH), 1768
(C=O), 1706 (C=O); 1H NMR (200 MHz, DMSO-d6): δ 9.10 (s, 1H, NH), 7.55–7.20 (m,
10H, Ph-H), 4.56 (s, 2H, CH2Ph), 0.75 (t, J = 7,3 Hz, 3H, CCH2CH3);
13
C NMR (50
MHz, DMSO-d6): δ 174.8 (C4), 156.2 (C2), 138.9, 136.9, 128.8, 128.2, 127.7, 127.6,
125.7, 67.2 (C5), 41.4, 31.6, 8.1.
3,5-Dimethyl-5-phenylhydantoin (20, C11H12N2O2). White crystalline solid; m.p.: 189–
191 °C (lit. m.p.: 188–190 °C [8]); yield: 40 %; IR (KBr, cm-1): ν 3262 (NH), 1783
(C=O), 1710 (C=O); 1H NMR (300 MHz, DMSO-d6): δ 8.90 (s, 1H, NH), 7.49–7.28 (m,
5H, Ph-H), 2.84 (s, 3H, NCH3), 1.67 (s, 3H, CCH3);
13
C NMR (75 MHz, DMSO-d6): δ
173.2 (C4), 153.6 (C2), 137.5, 126.2, 125.7, 123.2, 60.7 (C5), 22.7, 22.1.
6
3-Ethyl-5-methyl-5-phenylhydantoin (21, C12H14N2O2). White crystalline solid; m.p.:
108–110 °C (lit. m.p.: 109 °C [9]); yield: 62 %; (KBr, cm-1): ν 3259 (NH), 1783 (C=O),
1704 (C=O) cm-1; 1H NMR (300 MHz, DMSO-d6): δ 8.89 (s, 1H, NH), 7.48–7.29 (m,
5H, Ph-H), 3.38 (q, J = 7.1 Hz, 2H, CH2CH3), 1.66 (s, 3H, CCH3), 1.05 (t, J = 7.0 Hz,
3H, CH2CH3);
13
C NMR (75 MHz, DMSO-d6): δ 172.9 (C4), 153.3 (C2), 137.4, 126.3,
125.7, 123.2, 60.4 (C5), 30.6, 22.3, 11.0.
3-n-Propyl-5-methyl-5-phenylhydantoin (22, C13H16N2O2). White crystalline solid; m.p.:
98–100 °C (lit. m.p.: 100 °C [9]); yield: 53 %; IR (KBr, cm-1): ν 3261 (NH), 1782 (C=O),
1705 (C=O); 1H NMR (300 MHz, DMSO-d6): δ 8.89 (s, 1H, NH), 7.48–7.27 (m, 5H, PhH), 3.36 (t, J = 7.1 Hz, 2H, CH2CH2CH3), 1.67 (s, 3H, CCH3), 1.56-1.44 (m, 2H,
CH2CH2CH3), 0.76 (t, J = 7.3 Hz, CH2CH2CH3); 13C NMR (75 MHz, DMSO-d6): δ 173.2
(C4), 153.5 (C2), 137.5, 126.3, 125.7, 123.1, 60.4 (C5), 37.1, 22.7, 18.6, 8.7.
3-Isopropyl-5-methyl-5-phenylhydantoin (23, C13H16N2O2). White crystalline solid; m.p.:
107–109 °C; yield: 35 %; IR (KBr, cm-1): ν 3224 (NH), 1769 (C=O), 1699 (C=O); 1H
NMR (300 MHz, DMSO-d6): δ 8.83 (s, 1H, NH), 7.47–7.29 (m, 5H, Ph-H), 4.19–4.09
(m, 1H, CH(CH3)2), 1.64 (s, 3H, CCH3), 1.31-1.26 (d, J = 6,8 Hz, 6H, CH(CH3)2);
13
C
NMR (75 MHz, DMSO-d6): δ 173.0 (C4), 153.3 (C2), 137.5, 126.3, 125.7, 123.1, 59.7
(C5), 40.3, 22.6, 17.2.
3-n-Butyl-5-ethyl-5-phenylhydantoin (24, C14H18N2O2). White crystalline solid; m.p.: 88–
90 °C (lit. m.p.: 91 °C [9]); yield: 66 %; IR (KBr, cm-1): ν 3258 (NH), 1782 (C=O), 1705
(C=O); 1H NMR (300 MHz, DMSO-d6): δ 8.89 (s, 1H, NH), 7.48–7.30 (m, 5H, Ph-H),
3.38–3.32 (m, 2H, CH2CH2CH2CH3), 1.67 (s, 3H, CCH3), 1.48–1.41 (m, 2H,
CH2CH2CH2CH3), 1.25–1.33 (m, 2H, CH2CH2CH2CH3); 0.84 (t, J = 7.0 Hz,
CH2CH2CH2CH3);
C NMR (75 MHz, DMSO-d6): δ 173.1 (C4), 153.5 (C2), 137.4,
13
126.3, 125.7, 123.1, 60.4 (C5), 35.2, 27.3, 22.7, 17.0, 11.2.
3-Isobutyl-5-methyl-5-phenylhydantoin (25, C14H18N2O2). White crystalline solid; m.p.:
70–72 °C; yield: 44 %; IR (KBr, cm-1): ν 3293 (NH), 1777 (C=O), 1703 (C=O); 1H NMR
7
(300 MHz, DMSO-d6): δ 8.90 (s, 1H, NH), 7.48–7.30 (m, 5H, Ph-H), 3.18–3.16 (m, 2H,
CH2CH(CH3)2), 1.97–1.84 (m, 1H, CH2CH(CH3)2), 1.67 (s, 3H, CCH3), 0.80–0.75 (d, J =
7,0 Hz, 6H, CH2CH2(CH3)2);
13
C NMR (75 MHz, DMSO-d6): 173.3 (C4), 153.6 (C2),
137.5, 126.3, 125.7, 123.1, 60.4 (C5), 42.7, 24.7, 22.7, 17.5.
General Procedure for the Preparation of Compounds 8–10 [10].
To a solution of benzil (20.2 g, 96.2 mmol) and the appropriate urea (167 mmol) in
dimethyl sulfoxide (40 ml) 5 % potassium hydroxide solution (25 ml) was added under
stirring. The resulting mixture was refluxed for 2 h and poured into cold water. The
precipitate was filtrated and the filtrate was acidified with glacial acetic acid. The
resulting precipitate was collected, dried and recrystallized from ethanol.
3-tert-Butyl-5,5-diphenylhydantoin (8, C19H20N2O2). White crystalline solid; m.p.: 191–
193 °C (193–193,5 °C [11]); yield: 58 %; IR (KBr, cm-1): ν 3220 (NH), 1767 (C=O),
1712 (C=O); 1H NMR (200 MHz, DMSO-d6): δ 9.46 (s, 1H, NH), 7.44–7.17 (m, 10H,
Ph-H), 1.54 (s, 9H, CH3);
13
C NMR (50 MHz, DMSO-d6): δ 174.3 (C4), 156.4 (C2),
140.5, 128.8, 128.3, 126.9, 68.0 (C5), 57.2, 28.5.
3-Cyclopentyl-5,5-diphenylhydantoin (9, C20H20N2O2). White crystalline solid; m.p.:
132–134 °C; yield: 56 %; IR (KBr, cm-1): ν 3206 (NH), 1766 (C=O), 1707 (C=O); 1H
NMR (200 MHz, DMSO-d6): δ 9.64 (s, 1H, NH), 7.49–7.23 (m, 10H, Ph-H), 4.42–4.30
(m, 1H, CH-N), 1.85–1.80 (m, 6H, cPe-H), 1.53–1.50 (m, 2H, m, cPe-H); 13C NMR (50
MHz, DMSO-d6): δ 173.3 (C4), 155.5 (C2), 140.1, 128.8, 128.4, 126.8, 68.5 (C5), 51.0,
29.0, 25.0.
3-Cyclohexyl-5,5-diphenylhydantoin (10, C21H22N2O2). White crystalline solid; m.p.:
179–181 °C (lit. m.p.: 179–180 °C [10]); yield: 53 %; IR (KBr, cm-1): ν 3232 (NH), 1772
(C=O), 1712 (C=O); 1H NMR (200 MHz, DMSO-d6): δ 9.59 (s, 1H, NH), 7.50–7.22 (m,
10H, Ph-H), 3.89–3.77 (m, 1H, CH-N), 2.14–1.96 (m, 2H, cHx-H), 1.78–1.55 (m, 5H,
8
cHx-H), 1.34–1.03 (m, 3H, cHx-H); 13C NMR (50 MHz, DMSO-d6): δ 173.4 (C4), 155.5
(C2), 140.1, 128.8, 128.4, 126.9, 68.4 (C5), 50.8, 29.1, 25.5, 25.0.
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Murray RG, Whitehead DM, Le Strat F, Conway S: Facile one-pot synthesis of
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Suzuki H, Kneller MB, Rock DA, Jones JP, Trager WF, Rettie AE: Active-site
characteristics of CYP2C19 and CYP2C9 probed with hydantoin and
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4.
Hoffmann C: Synthesis of some 3-substituted 5,5-diphenylhydantoins. Bull Soc
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