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1993,58, 1687-1695
1687
A one-pot synthesis of [6 + 61, [6 + 71, and [6 + 81 bicyclic guanidines based on a new method of
dihydropyrimidoannelation, which involvesreaction of bia(iminophosphoranes)with aryl isocyanates
or isothiocyanates is described. The method is also applicable for the preparation of chiral bicyclic
guanidines.
(iminophosphoranes) in which both iminophosphorane
groups are directly linked to different aromatic or heteroaromaticrings. This new annelation approach, which
involves as the key step a consecutive aza Wittig-type
reaction/ [2 + 21 cycloaddition/transannulardihydropyrimido annelation process, has surprisinglybeen found to
be useful in the simultaneous formation of two fused
dihydropyrimidine rings in the synthesis of bicyclic
guanidines.
~~~
0022-3263/93/1958-1687$04.00/0
Molina et al.
Scheme I*
FT
R'
R'
bR5
R4
Ar-N=C=N-Ar
NAN
R*
compd
S
Sb
SC
H
CH3
CH3
Sd
H
Se
H
Sf
H
8
a
H
8b
H
&
H
8d
CH3
lla
H
llb
H
21a
21b
21c
230
23b
R*
H
H
H
H
CH3
H
H
CH3
H
H
H
CH3
R3
R4
R6
yield,%
mp,OC
H
H
CH3
H
H
CH3
H
CH3
H
CHs
CH3
H
45
22+231
218-220
87-89
235-21
263-265
105-106
306-307
246-248
242-244
22&222
250-251
241-248
161-162
105-106
97-98
289-290
298-299
H
H
H
H
H
H
H
'
NO2
H
H
H
H
H
CH3
H
H
N'
OPPh3
H
CH3
H
H
CH3
68
68
43
58
57
5
53
77
65
57
41
61
63
59
33
42
(ll)Dale,J.A.;Dull,D.L.;M~her,H.S.J.Org.Chem.lsBS,34,2543.
Applications of Bis(iminoph0sphoranes)
Scheme I1
10
11
a R~=F?=I?=H
b R'-H,I?=~,F?=H
13
12
Ph
14
15
Molina et al.
Scheme 111
H
16
41
17
sa
bPh3
Ar-N=PPh3
OPPh3
Ar-NCO
Ar-N=C=N-Ar
19
Ar
18
Scheme IV
R4
qNH2
O
20
'
R4
R4
22
Concluding Remarks
Applicatione of Bidiminophosphoranes)
4.30 (9, 1 H, J = 6.6 Hz), 7.12 (t, 2 H, J = 7.5 Hz), 7.26 (t, 1 H,
J = 7.5 Hz),7.41 (d, 1 H , J = 7.5 Hz);
NMR (CDCb) 6 23.6,
46.1,118.0,124.9,126.2,127.8,136.7
(8). 138.3 (8);massspectrum
m/z (relative intensity) 162 (M+, 51, 149 (33),119 (100). Anal.
Calcd for C&l&: C, 59.24;H, 6.21;N, 34.54. Found C, 59.15;
H, 6.12;N, 34.50.
Mosher amide of Id: lH NMR (CDCb) 6 1.45 (d, 3 H, J = 6.9
Hz), 1.49(d, 3 H, J = 6.9Hz), 3.40 (s,3 H), 3.48 (s,3 H), 5.22-5.28
(m, 2 H), 7.05-7.56 (m, 20 H); lgF NMR (CDCb) 6 6.91, 7.16.
Preparation of (S)-(-)-l-(~Azidophenyl)ethylamine(12).
The amine Id (1.05g and (R)-(-)-mandelic acid (0.99 g) were
dissolvedin a hot mixtureof ethylacetate (100mL) andmethanol
(2mL). The solution was cooled to room temperature. After 3
h the supernatant liquid was separated and the white solid was
recrystallized from ethyl acetate (60 mL) and methanol (1mL).
After 4 h at room temperature the separated solid was fiitered
and dried to give 0.90 g of the amine-mandelate salt. The salt
was suspended in 40mL of dichloromethane, 1 N NaOH (40mL)
was added, and the mixture was stirred for 35 min. The organic
layer was separated, the aqueous layer was extracted two more
times (CHZC12,20 mL), and the combined organic extra& were
dried over MgSO4. The Solvent was removed to give (&-l-(oazidopheny1)ethylamine(0.42g, 90% ). The a-methoxy-a-phenyla-(trifluoromethy1)acetamideofthis material was prepared from
(R)-(+)-MPTA and DCC and analyzed by lH NMR to reveal a
diastereomeric ratio of W10,the major isomer corresponding to
the (S)-1-(0-azidopheny1)ethylamine. A third recrystallization
of the amine mandelate from ethyl acetate (50mL) and methanol
(0.5mL) afforded 0.54 g of the salt, which upon basification
provided (5')-(-)-1-(0-azidopheny1)ethylamine (12):[(YI2OD-15.go
[c 6.66 1
P g/mL (CHdW, 97% eel.
Mosher amide of 12: 'H NMR (CDCg) 6 1.49 (d, 3 H, J = 6.9
Hz), 3.48 (8, 3 H), 5.20-5.29 (m, 1 H), 7.07-7.42 (m, 10 H); lBF
NMR (CDC1.q) 6 6.91.
Preparation of Bis(~azidobenzy1)amine.A mixture of
o-azidobenzyl chloride (6.70 g, 40 mmol) and liquid ammonia
was kept 48 h in a sealed tube stored at room temperature. The
excess of ammonia was removed by evaporation, water (100mL)
was added, and the organic layers were extracted with dichloromethane (3 x 30 mL) and dried over MgSO4. The solvent was
removed under reduced pressure, and the residue was chromatographed (silica gel; ethyl acetateh-hexane (1:l)and then
ethanol) to give tris(o-azidobenzy1)amine (27% ), bis(o-azidobenzy1)amine (37%), and o-azidobenzylamine (la)(25%).
Bis(~azidobenzy1)amine:yield 37% ;mp 42-43 O C ; colorless
needles (ether); IR (Nujol) 3324,2133cm-l; 'H NMR (CDCb) 6
1.99 (e, 1 H), 3.70 (8, 4H), 7.04-7.13 (m, 4 H), 7.23-7.33 (m, 4 H);
19c NMR (CDCb) 6 48.9,118.1, 124.7, 128.4, 130.3, 131.4 (e),
138.2 ( 8 ) ; mass spectrum m/z(relative intensity) 279 (M+,5),106
(loo),91 (63). Anal. Calcd for Cl4H13N7: C, 60.20; H, 4.69; N,
35.10. Found C, 60.09; H, 4.65; N, 34.99.
General Procedure for the Preparation of the Imines 3,
6,and9. Method A. Toasolutionofthecorrespondingaldehyde
2a,2b,5-azido-4-formyl-3-methyl-l-phenyl-W-pyrmle,
or 4 4 do-5-formyl-2-phenylthiazole
(10mmol) in 25 mL of dry ethanol
was added the corresponding benzylamine 1 (10mmol) and a
catalytic amount of acetic acid. The reaction mixture was stirred
at room temperature for 12h, and the separated solid was collected
and crystallized.
Method B. A mixture of o-azidoacetophenone 2c (0.80g, 5
mmol) and the corresponding benzylamine 1 (5"01)
was kept
at room temperature, in the presence of 4A molecular sieves and
MgSO,, until the band corresponding to the carbonyl group
disappeared in the IR of the mixture. The ketimines prepared
by this method (3c, 3 0 were used without purification in the
next step.
3 b yield 82%; mp 59-60 OC; colorless prisms (ethanol); IR
(Nujol) 2129,1640cm-1; 1H NMR (CDCb) 6 1.50 (d, 3 H, J = 6.6
Hz), 2.33 (e, 3 H), 4.85 (4,1 H,J = 6.6 Hz),7.03 (d, 1 H, J = 8.2
Hz), 7.11-7.29 (m, 4 H), 7.68 (dd, 1 H, J = 1.6,7.7 Hz), 7.86 (d,
1 H, J =1.6 Hz), 8.66 (8, 1 H);1% NMR (CDCb) 6 20.8,23.8,63.7,
118.1,118.3,125.1,127.1(a), 127.9,128.0,128.1,132.6,134.7 (E),
136.4 (a), 136.8 (a), 137.1 (E), 155.7;mass spectrum mlz (relative
intensity) 305 (M+, 7). 234 (loo), 91 (89). Anal. Calcd for
C&lsN7: C, 62.94;H, 4.95;N, 32.11. Found C, 62.80;H, 4.89;
N, 32.03.
Molina et al.
3d yield 85% ;mp 58 OC; colorlessprisms (ethanol);IR (Nujol)
2129, 2084,1641cm-I; 'H NMR (CDCb) 6 2.29 (8, 3 H),4.69 (8,
2 H), 7.00-7.17(m, 5 H), 7.41 (dt, 1 H, J = 1.6,8.3Hz), 8.03 (d,
1 H, J = 7.8 Hz), 8.67 (8, 1 H); '9c NMR (CDCls) 6 20.9,60.4,
118.0,118.4,124.9,127.3(a), 128.1,129.0,130.1(8),130.7,131.8,
134.6 (a), 135.1 (e), 139.7 (e), 157.8; maas spectrum m/z(relative
intensity) 291 (M+, 5), 234 (100). 91 (65). Anal. Calcd for
Cld3&: C, 61.85;H, 4.M); N, 33.66. Found C, 61.78;H, 4.40;
N, 33.74.
3e: yield 83% ;mp 78OC; colorleasprisms (ethanol); IR (Nujol)
2129,2095,1643 cm-';'H NMR CCDCb) 6 2.30 (e, 6 H), 4.68 (e,
2 H), 7.00-7.24(m, 5 HI, 7.84 (d, 1 H, J = 2.2 Hz), 8.65 (e, 1 HI;
19c NMR (CDCls) 6 20.7,20.9,60.5,118.0,118.3,126.9
(a), 128.2,
129.0,130.1 (e), 130.8,132.7,134.6 (a), 134.7 (e), 135.2 (a), 137.1
(e), 158.0; mass Spectrum m/z (relative intensity) 305 (M+, 7),
248 (loo),91 (80). Anal. Calcd for Cl6Hl87: C, 62.94;H, 4.96;
N, 32.11. Found: C, 62.81;H, 4.89; N, 32.07.
68: yield 81% ; mp 97-98 OC; colorless needles (ethanol); IR
(Nujol) 2194,1649 cm-l; lH NMR (CDCb) 6 2.42 (8, 3 H), 4.71
(e, 2 H),7.07-7.59 (m, 9 H), 8.36 (e, 1 H); 13CNMR (CDCb) 6 13.0,
60.8,llO.l (e), 118.0,124.0,124.8,127.7,128.3,128.9,130.1,130.8
(e), 136.5 (a), 137.8 (e), 149.7 (s), 153.3,one quaternary carbon
was not observed; mass spectrum m / z (relative intensity) 357
(M+,
7), 329 (86),77 (100). Anal. Calcd for C I ~ H I ~ N
C,~60.50;
:
H, 4.23;N, 35.27. Found: C, 60.47;H, 4.15; N, 35.19.
6 b yield 76% ;mp 98"C; colorlessprisms (ethanol);IR (Nujol)
2135,1652 cm-1; lH NMR (CDCls) 6 2.26 (8, 3 H), 2.37 (a, 3 H),
4.63 (e, 2 H), 6.96-7.54 (m, 8 H), 8.32 (e, 1 H); 13CNMR (CDCb)
6 13.1, 20.9, 61.0,110.2 (s), 118.0, 124.1,127.8,129.0,130.5 (a),
130.9,134.6 (e), 135.1 (81, 136.6 (a), 137.9 (e), 149.8 (a), 153.2 (e),
one aromatic CH was not observed; mass spectrum m/z (relative
intensity) 371 (M+, 5), 149 (1001,77 (91). Anal. Calcd for
ClgH17Ng: C, 61.45;H, 4.61;N, 33.94. Found C, 61.34;H, 4.49;
N, 33.85.
6c: yield 83%; mp 113-114 OC; colorless prism (ethanol); IR
(Nujol) 2146,1644,1290cm-l; 'H NMR (CDCS) 6 2.44 (s,3H),
4.75 (8, 2 H), 7.32-7.65 (m, 6 H), 7.93-7.99 (m, 2 H), 8.42(8, 1 H);
13CNMR (CDCls) 6 13.1,60.3,109.9(s), 112.8,119.7,124.1,127.9,
129.0, 130.3,136.7 (e), 137.7 (e), 138.3 (a), 139.1 (e), 147.6 (a),
149.9 (a), 154.6;mass spectrum m/z(relative intensity) 402 (M+,
71,183 (1001,163 (44). Anal. Calcd for Cl8H14NlOOZ: C, 53.73;
H, 3.51;N, 34.81. Found C, 53.61;H, 3.47;N, 34.70.
6d: yield 75%; mp 67-68 OC; colorless prisms (ethanol); IR
(Nujol) 2130,1639cm-l; 'H NMR (CDCls) 6 1.51 (d, 3 H, J = 6.6
Hz), 2.40 (s,3H), 4.77 (9,1 H, J = 6.6 Hz), 7.14 (t, 2 H, J = 7.9
Hz), 7.26 (M,1 H, J =1.6,7.7Hz), 7.33 (d, 1 H, J =7.1 Hz), 7.43
(t, 2 H, J = 7.8 Hz), 7.56 (d, 2 H, J = 8.8 Hz), 7.72 (d, 1 H, J =
7.9 Hz), 8.37 (8, 1 H); 13C NMR (CDCg) 6 13.0,24.7,64.9,110.2
(e), 117.9,124.1,125.1,127.7,127.9,128.2,128.9,136.3 (E), 136.5
(s), 136.6 (a), 137.9 (a), 149.9 (a), 15l.l;massspectrumm/z(relative
intensity) 371 (M+, 6), 118 (89), 91 (100). Anal. Calcd for
ClgH1.rNe: C, 61.44;H, 4.61;N, 33.94. Found: C, 61.38;H, 4.50;
N, 33.85.
98: yield 935% ;mp 114OC; yellow needles (ethanol); IR (Nujol)
2121,1623,1284cm-l; lH NMR (CDCl3)6 4.68 (e, 2 H), 7.09-7.16
(m, 2 H), 7.29-7.33 (m, 2 H), 7.39-7.45 (m, 3 H), 7.91-7.94 (m,
2H),8.32(~,1H);~~CNMR(CDCls)659.9,118.1,118.7(s),125.0,
126.5, 128.6,129.1, 130.1, 131.3, 132.7 (a), 138.0 (e), 138.3 (e),
149.3 (e), 151.8,168.8( 8 ) ; mass spectrum m/z (relative intensity)
360 (M+, 5),84 (1001,77 (87). Anal. Calcd for CI~HIZNBS:
C,
66.66,H, 3.36; N, 31.09. Found: C, 56.54; H, 3.29;N,31.00.
9b: yield 86%;mp 131 OC; yellow prisms (ethanol); IR (Nujol)
2129, 1622, 1238 cm-l; lH NMR (CDCls) 6 2.30 (8, 3 H), 4.64 (e,
2 H), 6.99-7.09 (m, 3 H), 7.37-7.47 (m, 3 H), 7.89-7.94 (m, 2 H),
8.31 (8, 1 H);13C NMR (CDCls)6 20.9,59.9,118.0,118.8(8). 126.5,
129.1,129.2,129.7 (a), 130.8,131.2,132.6(a), 134.7 (e), 135.2 (e),
149.3 (a), 151.6,168.7 (a); mass spectrum m/z(relative intensity)
374 (M+,6),145 (94),83 (100). Anal. Calcd for Cldil4N& C,
57.74;H, 3.77; N, 29.93. Found: C, 57.65;H, 3.71;N, 29.87.
General Procedure for the Preparation of the Bir(iminophosphoranes)4,7,and 10. Method A. To a solution
of triphenylphoephine (2.62g, 10 mmol) in 25 mL of dry ether
was added bis(o-azidobenzy1)amine(1.39g, 5 mmol) in the same
solvent. The reaction mixture was stirred at room temperature
for 12 h, and the separated solid was filtered and crystallized.
Only 4a was prepared following this method.
Applications of Bis(iminophosphoranes)
Molina et al.
(CDC13)6 2.15 (s,3H), 5.12 (br s, 4 H), 6.44-7.72 (m, 42 H), 8.8
8c: yield 77%; mp 246 "C dec; orange prisms (benzene); IR
(a, 1 H); 13C NMR (CDC13)6 20.7, 46.5 (v br), 118.5 (br), 122.0,
(Nujol) 1634,1589,1579 cm-1; 1H NMR (DMSO-de) 6 2.07 (s,3
127.6 (br), 129.2 (d, Jp-c = 11.5 Hz), 130.5 (br), 131.5 (s),
H), 4.45 (e, 2 H), 4.53 ( ~ ,H),
2 7.16 (t,1 H, J =: 7.4 Hz), 7.32-7.43
132.3 (d, Jp-c = 2.0 Hz), 132.5 (s), 132.6, 132.8,133.2 (d, Jp-c
(m, 4 H), 7.72 ( 8 , 1 H), 7.99 (d, 2 H, J = 8.2 Hz), 9.99 (e, 1 H);
= 9.4 Hz), 138.6 (a), 149.4 (8, br), 157.1 (e), Ci was not observed;
13C NMR (DMSO-ds) 6 12.2,47.0,49.1, 94.2 (S), 107.8, 115.6,
31P NMR (CDC13) 6 2.06 (br), 6.46 (br); mass spectrum m/z
120.2,124.4,124.6(a), 126.8,128.5,137.6 (s), 139.9 (s), 142.9 (s),
(relative intensity) 366 (12),183 (92),133 (371,108(58),91 (481,
146.3(a), 147.5(a), 148.9(a); massspectrum m/z (relativeintensity)
77 (100). Anal. Calcd for CawN4OP2: C, 79.06;H, 5.72;N,
360 (M+, 5), 105 (461, 97 (541,55 (100). Anal. Calcd for
6.36. Found C, 78.81;H, 7.58; N, 6.20.
C&&&
c , 63.33;H, 4.48;N, 23.32. Found C, 63.30; H,
Preparation of 2-(eAzidophenyl)ethylamine (20). The
4.39;N, 23.25.
amine 20 was prepared from 2-(o-azidopheny1)ethanoll4following
8 d yield 65% ;mp 220-222 "C; colorless prisms (chloroform/
the method described for the preparation of Id.
ether); IR (Nujol) 3216,1632,1576cm-l; 'H NMR (CDCl3)6 1.39
N-[2-(eAzidophenyl)ethyl]phthalimide: yield 64% ; mp
(d, 3 H, J = 6.6 Hz), 2.25 (s,3H), 4.20 (q,1 H, J = 6.6 Hz), 4.58
119-120 OC; colorlessprisms (ethyl acetateln-hexane);IR (Nujol)
(d, 1 H, J = 11.2 Hz), 4.69 (d, 1 H, J = 11.2 Hz), 6.34 (d, 1 H,
2129,1772, 1358 cm-l; 1H NMR (CDCl3) 6 2.96 (t, 2 H, J = 6.9
J = 7.9 Hz), 6.79-7.05 (m, 4 H), 7.27 (t, 2 H, J = 7.5 Hz), 7.90
Hz), 3.92 (t, 2 H, J = 6.9 Hz), 6.96-7.29 (m, 4 H), 7.66-7.85 (m,
(d, 2 H, J = 7.7 Hz), 9.12 (8, 1 H); 13CNMR (CDC13) 6 12.6,20.4,
4 H); 13C NMR (CDC13) 6 30.2, 37.9, 118.1,123.1,124.8, 128.2,
46.0, 56.5, 94.5 (a), 113.8, 121.7,121.9, 122.7 (a), 124.8, 125.2,
129.5 (a), 131.0,132.0(s),133.9,138.5(a), 168.1 (8);massspectrum
128.1,128.5,134.8(s), 139.6 (s), 143.9(51,146.2(a), 149.8 (a); mass
m/z (relative intensity) 292 (M+, 7), 264 (29),117 (100). Anal.
spectrummlz (relative intensity) 329 (M+,921,328(100),77(91).
Calcd for C&12N4oZ: C, 65.75;H, 4.14; N, 19.16. Found c,
Anal. Calcd for CZ0Hl9HS:C, 72.92;H. 5.81;N, 21.26. Found
65.64;H, 4.10;N, 19.08.
C, 72.81;H, 5.73;N, 21.28.
24eAzidopheny1)ethylamine (20): yield 83% ;oil; IR 2126,
1 la: yield 57% ;mp 250-251 OC; yellow prisms (benzene); IR
1491,1287 cm-1; 1H NMR (CDC13) 6 2.24 (8, 2 H), 2.75 (t, 2 H,
(Nujol) 3250,1624,1603 cm-1; IH NMR (CDC13 + TFA) 6 4.75
J = 6.9Hz), 2.90 (t,2H,J = 6.9Hz),7.02-7.35(m,4H); 13CNMR
(a, 2 H), 4.91 (a, 2 H), 7.02-7.34 (m, 4 H), 7.49-7.64 (m, 3 H), 7.77
(CDC13) 6 35.1,42.1,118.0,124.6,127.6,130.9,130.9(s), 138.0 (8);
(d, 2 H, J = 7.5 Hz), 9.76 (a, 1 H); 13CNMR (CDC13 + TFA) 6
mass spectrum mlz (relative intensity) 162 (M+, 19), 149 (44),
48.1,50.6,103.1(e), 115.5 (a), 116.3,126.0,126.9,127.0,128.8
(a),
117 (100). Anal. Calcd for CsHloN4: C, 59.24;H, 6.21;N, 34.54.
130.0,130.2,130.3 (s), 133.4,140.4 (a), 146.6 (s), 171.9 ( 8 ) ; mass
Found: C, 59.15;H, 6.12;N, 34.43.
spectrum m/z (relative intensity) 318 (M+,73),317 (loo),91 (33).
Preparation of 3-(eAzidophenyl)propylamine (22). To
Anal. Calcd for C18H14N4SC, 67.90;H, 4.43;N, 17.60. Found
(4.53 g, 30 mmol) in
a solution of 3-(0-aminophenyl)propanol~~
C, 67.75;H, 4.48;N, 17.48.
180mL of 2 N HCl ccoled at -5 "C was added dropwise a solution
11b: yield 41 % ;mp 250 "C dec; yellow prisms (benzene); IR
of sodium nitrite (2.76g, 40 mmol) in 20 mL of water. After 30
(Nujol) 3250,1629,1601 cm-1; 1H NMR (CDC13 + TFA) 6 2.31
min of stirring, a solution of sodium azide (2.60g, 40 mmol) in
(s,3H), 4.73 (a, 2 H), 4.91 (a, 2 H), 6.91-6.97 (m, 2 HI, 7.13 (d,
20 mL of water was added dropwise, and stirring was continued
1 H, J = 8.0Hz), 7.51-7.67 (m, 3 H), 7.78 (d, 2 H, J = 7.7 Hz),
for 3 h. The mixture was extracted with dichloromethane (3X
9.60 (s, 1 H); 1'C NMR (CDC13 TFA) 6 20.6,47.9,50.7, 103.7
30mL), and the organic layers were washed with water and dried
(a), 115.3(s), 116.3,126.4(a), 127.1,127.7,128.5(s),130.1,130.8,
over MgS04. The solvent was removed, and the resulting oil was
133.7,137.6(a), 140.3 (a), 146.4(e), 172.1 (a); mass spectrum mlz
purified by column chromatography (silica gel, etherh-hexane
(relative intensity) 332 (M+, 65), 331 (100). Anal. Calcd for
(7:3))to give 3-(eazidophenyl)propanol: yield 45% oil; IR
C19H&S: C,68.65;H,4.85;N,
16.85. Found: C,68.54;H,4.72;
2125,1491,1287cm-1; 1H NMR (CDC13) 6 1.75-1.92 (m, 2 H),
N, 16.76.
2.03 (a, 1 H), 2.65 (t, 2 H, J = 7.6 Hz), 3.62 (t, 2 H, J = 6.3 Hz),
Preparation of the Chiral Guanidines 13-15. The chiral
7.01-7.34 (m, 4 H);
NMR (CDC13) 6 27.3,33.1,62.0,118.1,
guanidines 13-15 were prepared from the (S)-(-)-1-(0-azidophe(a), 139.5 (6);massspectrum mlz (relative
124.9,127.5,130.6,133.3
ny1)ethylamine (12)followingthe procedure described above for
intensity) 177 (M+,32), 149 (100). Anal. Calcd for CgHllN30
the preparation of the corresponding racemic guanidine.
C, 61.00;H, 6.26;N, 23.71. Found C, 60.89;H, 6.30;N, 23.65.
13: yield 62%; [ a l Z 0
+526.7"
~
[c 4.65
glmL (CHzCldI.
The amine 22 was prepared from 3-(o-azidophenyl)propanol
14: yield 65%;
+463.2" [c 4.75 le3g/mL (CH2Clz)I.
following the procedure described for the preparation of Id.
15: yield 60%; [(Y]%D+223.0 [c 4.95
g/mL (CHzC12)I.
N-[3-(eAzidophenyl)propyl]phthalimide: yield 74% ;mp
Preparation of the Intermediate 16. Method A. To a
88-89 OC; colorless prisms (ethyl acetateln-hexane); IR (Nujol)
solution of 4a (0.75g, 1 mmol) in 10 mL of dry dichloromethane
2118,2094, 1714 cm-l; lH NMR (CDCl3) 6 1.92-2.02 (m, 2 H),
was added p-methylphenyl isocyanate (0.13g, 1 mmol). The
2.62(t,2H,J=8.2Hz),3.72(t,2H,J=7.1Hz),7.03-7.21(m,
reaction mixture was stirred at room temperature for 1 h, the
4 H), 7.68-7.71 (m, 2 H), 7.82-7.84 (m, 2 H); 13CNMR (CDC13)
solvent was removed under reduced pressure, and the resulting
6 28.5,28.8,37.8,118.1,123.2,124.7,127.5,130.2,132.1
(s), 132.5
material was purified by column chromatography (silicagel; ethyl
(s), 133.9, 137.9 (a), 168.4 ( 8 ) ; mass spectrum mlz (relative
acetate) to give 16 as a white amorphous solid in 85% yield.
intensity) 306 (M+, 5), 130 (67), 118 (100). Anal. Calcd for
Method B. Bis(o-azidobenzy1)amine (0.56g, 2 mmol) was
C17H14N402: C, 66.66;H, 4.60; N, 18.29. Found: C, 66.53;H,
dissolved in 10 mL of dry dichloromethane, and p-methylphenyl
4.51;N, 18.33.
isocyanate (0.26g, 2 mmol) was added. The mixture was stirred
34 eAzidopheny1)propylamine (22):yield 92% ;oil; IR3375,
at room temperature for 1 h, the solvent was removed to dryness,
3279,2123 cm-1; 1H NMR (CDCl3) 6 1.63-1.79 (m, 2 H), 2.13 (a,
and the residue was chromatographed (silicagel; etherln-hexane
2 H), 2.60 (t,2 H, J = 7.3 Hz), 2.69 (t,2 H, J = 7.0 Hz), 7.01-7.34
(1:l)) to give l,l-bis(eazidobenzyl)-3-(4-methylphenyl)(m, 4 H);l3C NMR (CDCls)6 28.3,34.2,41.6,117.9,124.6,127.2,
urea: yield 92%; mp 114-115 "C; colorless prisms (ether); IR
130.2,133.4(a), 137.8(e); mass spectrum mlz (relative intensity)
(Nujol) 3358,2129,1662 cm-1; lH NMR (CDC13) 6 2.26 (a, 3 H),
176 (31),148 (100). Anal. Calcd for CgH12Nd: C, 61.34;H, 6.86;
4.52 (e, 4 H), 6.89 ( 8 , 1 H), 7.04 (d, 2 H, J = 8.3 Hz), 7.09-7.19
N, 31.79. Found: C, 61.25;H, 6.77;N, 31.70.
(m,6H),7.30-7.35(m,4H);13CNMR(CDCl3)620.7,46.2,118.2,
General Procedure for the Preparation of the Guanidines
120.1,125.3,128.5 (s), 129.0, 129.4, 129.5, 132.6 (s), 136.6 (a),
21 and 23. The corresponding carbonyl compound 2 (5 mmol)
137.8 (e), 155.9 (a); mass spectrum mlz (relative intensity) 412
was dissolved in 20 mL of dry ether, and MgSO4 (for o-azidoac(M+, 7), 133 (49), 119 (75), 106 (100). Anal. Calcd for
etophenone 4-Amolecular sieves were added also) and then the
C22H20N~O:
C, 64.07;H, 4.88;N, 27.16. Found: C, 64.01;H, 4.73;
adecuate amine 20 or 22 ( 5 mmol) was added. The mixture was
N, 27.08.
kept at room temperature until the band corresponding to the
To a solution of triphenylphosphine (0.52g, 2 mmol) in 10mL
carbonyl group disappeared in the IR of the mixture.
of dry dichloromethane was added, dropwise, a solution of 1,lAfter removal the MgS04,the resulting solution of the crude
bis(2-azidobenzyl)-3-(4methylphenyl)urea(0.41g, 1 mmol) in the
imine was added dropwise to a solution of triphenylphosphine
same solvent (5 mL). The solution was stirred at room tem(2.62g, 10 mmol) in 20 mL of dry ether. The new mixture was
perature for 3h, the solvent was removed under reduced pressure,
stirred at room temperature for 12 h. The separated solid was
and the solid was purified in the same way as in method A to
filtered and dried.
afford 16: yield 85%;IR (Nujol) 3443,1651,1107cm-l; 'H NMR
Applications of Bis(iminophoephoranes)
This material was dissolved in a mixture of dry dichloromethane and dry methanol (20/20 mL) and cooled at 0 "C.
was added. After
Then sodium borohydride (0.75 g, 20 "01)
30 min a second batch of sodium borohydride (0.75g, 20 mmol)
was added and stirriig was continued 1 h. The solvent was
removed under reduced pressure, and the residue was treated
with cold water, filtered, and dried, initially at room temperature
and then at 70 OC to give the corresponding bie(iminophoephorane) substituted secondary amine in an overall yield of 30-81 % ,
which was used without purification in the next step. To a
solution of this bis(iminophosph0rane) (1 "01)
in 20 mL of dry
benzene was added pmethylphenyl isocyanate (2 "01).
The
reaction mixture was stirred at reflux temperature for 4 h.
Guanidinea 21 were isolated from the reaction mixture by the
following procedure: after the mixture was cooled the solvent
was removed under reduced pressure, the resulting material was
treated with n-hexane (3 x 25 mL), and the residue was
chromatographed over eilica gel using as eluent first ethanol and
then ethanol/aqueous ammonia (955).
Guanidines 23 were isolated from the cold reaction mixture
by filtration.
21a: yield 61%;mp 161-162 "C; colorless prisms; IR (Nujol)
1632,1585, 1570 cm-I; 1H NMR (CDCb) 6 3.12 (t, 2 H, J = 5.0
Hz), 3.68 (t,2 H, J = 5.0 Hz), 4.43 (8, 2 H), 6.85-7.14 (m, 9 H);
1% NMR (CDCb) 6 33.5,52.4,52.5,119.0,120.7 (e), 121.6,121.7,
121.8, 124.6, 127.5, 128.3 (e), 128.4, 130.0, 141.5 (s), 142.5 (e),
152.0 (e); maw spectrum m/z (relative intensity) 249 (M+, loo),
248 (831,233 (29). Anal. Calcd for ClSHlaNs: C, 77.08; H, 6.06;
N, 16.85. Found: C, 76.97; H, 6.01; N, 16.77.
21b yield 63%;mp 105-106 "C;colorless prisms; IR (Nujol)
1635, 1584, 1226 cm-'; lH NMR (CDCb) 6 2.27 (8, 3 H), 3.13 (t,
2 H, J = 4.9 Hz), 3.71 (t, 2 H, J = 4.9 Hz), 4.45 (s,2 H), 5.71 (e,
1 H), 6.w7.07 (m, 7 H ) ; W NMR (CDCb) 6 20.9,33.3,52.5,52.9,
117,9,119.5 (s), 121.6, 122.7, 125.4, 127.8,128.3(e), 129.3, 129.9,
132.6(s), 136.6(s), 139.7 (s), 151.4 (e);mawspectrumm/z (relative
intensity) 263 (M+, loo), 262 (96),91 (25). Anal. Calcd for
C17H17Na: C, 77.54;H, 6.50, N, 15.95. F o ~ C,
d 76.47; H, 6.45;
N, 15.90.