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A. Goblyos et al. / Tetrahedron 58 22002) 1011±1016
1015
N-Benzyloxycarbonyl-b-alanine anilide :21.96 g, 0.07 mol)
was suspended in 33% HBr in AcOH :90mL) and the
mixture was left to stand at room temperature for an hour
with occasional shaking. The crystals of 3 hydrobromide
that were formed were ®ltered off and dissolved in ice-
cold water :75 mL). The solution was made alkaline with
20% NaOH and extracted with CHCl3 :5£100 mL). The
combined organic phases were dried over Na2SO4 and
evaporated under reduced pressure. The crystalline residue
was puri®ed by column chromatography on silica gel
:eluent: toluene±MeOH1:1). Yield 9.10g :74%), mp
[M11]1. Analysis: calculated for C13H16Cl2N2: C, 57.58;
H, 5.95; N, 10.33; found: C, 57.33; H, 5.67; N, 10.21.
Pure diamine bases 9±11 were obtained from the above
dihydrochlorides by alkaline treatment :20% NaOH),
extraction :CH2Cl2) and evaporation under reduced
pressure. The free bases were dried in a vacuum desiccator
for 24 h before further transformations.
4.2. General method for the synthesis of 2-arylhexa-
hydropyrimidines -14±16) and 2-aryl-1,2,3,4-tetra-
hydroquinazolines -17±19)
1
190±1928C, H NMR :CDCl3) d: 2.47 :m, 2H, CH2CO),
3.12 :m, 2H, NCH2), 7.07 :m, 1H, C6H5), 7.31 :m, 2H,
C6H5), 7.54 :d, 2H, J7.8 Hz, C6H5), 9.92 :br s, 1H, NH);
IR nmax 1659, 1599, 1556, 1498, 1445, 751 cm21; MS m/z
165 [M11]1. Analysis: calculated for C9H12N2O: C, 65.83;
H, 7.37; N, 17.06; found: C, 65.71; H, 7.12; N, 16.87.
To a solution of the appropriate diamine :4, 9±13, 3 mmol)
in absolute MeOH :20mL), an equivalent amount of
aromatic aldehyde was added :in the case of liquid
aldehydes, a freshly distilled sample was used), and the
mixture was left to stand at ambient temperature for 1 h.
The solvent was evaporated off and the evaporation was
repeated after the addition of toluene :10mL). The oily
products were dried in a vacuum desiccator for 24 h. The
NMR spectra proved that the purities of these compounds
were greater than 95%. Crystalline products were ®ltered off
and recrystallized. All of the recrystallized new compounds
:17a, 18a±g, 19a±f) gave satisfactory data on elemental
analysis :C, H, N^0.3%).
4.1.2. General method for the synthesis of N-phenyl-
propylenediamine -4) and 2--methyl-, isopropyl- or
phenylaminomethyl)anilines -9±11). To a stirred suspen-
sion of LiAlH4 :11.39 g, 0.30 mol) in dry THF :350 mL), a
solution of b-alanine anilide :3) or the appropriate 2-amino-
N-substituted-benzamide :6±8) :0.10 mol) in dry THF :3:
200 mL, 6±8: 50mL) was added dropwise. The mixture
was stirred and re¯uxed for 7.5 h and then cooled and the
excess of LiAlH4 was decomposed by addition of a mixture
of water :20mL) and THF :50mL). The inorganic salts
were ®ltered off and washed with EtOAc :3£200 mL).
The combined organic ®ltrates and washings were dried
over Na2SO4 and evaporated under reduced pressure to
give the crude diamines as oily :4, 9, 10) or crystalline
products :11, mp 80 ±818C, lit.9c mp 81±838C).
1
4.2.1. H NMR spectroscopic data on 1-isopropyl-2--4-
bromophenyl)hexahydropyrimidine -15c) and 3-iso-
propyl-2--4-methoxyphenyl)-1,2,3,4-tetrahydroquinazo-
line -18f) in CDCl3. The protons of the open form :A) are
numbered according to the corresponding protons of the
ring form :B) :d in ppm, in brackets the multiplicity,
couplings in Hz and assignment, respectively).
Crude diamine 4 was distilled in vacuo. Yield 14.08 g
:93%). Bp 100±1058C/1±2 mm. The H NMR data on the
1
Compound 15cA: 1.00 :d, 6H, J6.3 Hz, 2£CH3), 1.80±
1.87 :m, 2H, 5-CH2), 2.66 :t, 2H, J7.0Hz, 6-C H2), 2.68±
2.80:m, 1H, C H), 3.63 :t, 2H, J6.5 Hz, 4-CH2), 7.52 :dd,
4H, J20.3, 8.5 Hz, C6H4), 8.19 :s, 1H, NvCH);
Compound 15cB: 0.75 :d, 3H, J6.5 Hz, CH3), 0.85 :d,
3H, J6.8 Hz, CH3), 1.59±1.71 :m, 2H, 5-CH2), 2.39±
2.45 :m, 1H, 6-CH2), 2.62±2.74 :m, 1H, CH), 2.63±2.72
:m, 1H, 4-CH2), 3.01±3.05 :m, 1H, 6-CH2), 3.13 :t, 1H,
J6.96 Hz, 4-CH2), 4.14 :s, 1H, NCHN), 7.29 :d, 2H,
J8.1 Hz, C6H4), 7.42 :d, 2H, J8.1 Hz, C6H4).
product correspond to the literature13 data.
For puri®cation, crude diamines 9±11 were converted to the
crystalline dihydrochlorides by treatment of their ethanolic
:10mL) solutions with an excess of 22% ethanolic HCl and
Et2O. The crystalline dihydrochlorides were ®ltered off and
recrystallized from MeOH±Et2O.
Compound 9: yield 16.35 g :78%), mp 210±2128C :lit.14 mp
236±2388C), 1H NMR :D2O) d: 2.84 :s, 3H, CH3), 4.36 :s,
2H, CH2), 7.46 :m, 1H, C6H4), 7.50±7.61 :om, 3H, C6H4);
IR nmax 2773, 2565, 1538, 1496, 1454, 766, 754 cm21; MS
m/z 137 [M11]1. Analysis: calculated for C8H14Cl2N2: C,
45.95; H, 6.75; N, 13.40; found: C, 45.68; H, 6.57; N, 13.26.
Compound 18fA: 1.06 :d, 6H, J6.2 Hz, 2£CH3), 2.77±
2.80:m, 1H, C H), 3.87 :s, 3H, OCH3), 3.90:s, 2H, C H2),
6.96±7.05 :om, 3H, C6H4), 7.14±7.18 :m, 1H, C6H4), 7.26±
7.28 :m, 1H, C6H4), 7.31±7.32 :m, 1H, C6H4), 7.85 :d, 2H,
J8.7 Hz, C6H4), 8.38 :s, 1H, NvCH); Compound 18fB:
1.01 :d, 3H, J6.4 Hz, CH3), 1.17 :d, 3H, J6.5 Hz, CH3),
2.89±2.80:m, 1H, C H), 3.76 :s, 2H, CH2), 3.79 :s, 3H,
OCH3), 4.14 :br s, 1H, NH), 5.14 :s, 1H, NCHN), 6.54 :d,
1H, J7.9 Hz, C6H4), 6.63±6.66 :m, 1H, C6H4), 6.83±6.90
:om, 3H, C6H4), 6.96±7.04 :m, 1H, C6H4), 7.37±7.40:m,
2H, C6H4).
Compound 10: yield 18.65 g :79%), mp 193±1958C :lit.15
1
mp 1918C), H NMR :D2O) d: 1.42 :d, 6H, J6.6 Hz,
2£CH3), 3.62 :m, 1H, CH), 4.36 :s, 2H, CH2), 7.46 :m,
1H, C6H4), 7.50±7.63 :om, 3H, C6H4); IR nmax 2800,
1561, 1502, 1444, 1392, 1145, 763, 754 cm21; MS m/z
165 [M11]1. Analysis: calculated for C10H18Cl2N2: C,
50.64; H, 7.65; N, 11.81; found: C, 50.38; H, 7.41; N, 11.73.
1
Compound 11: yield 23.79 g :88%), mp 165±1678C, H
Acknowledgements
NMR :D2O) d: 4.76 :s, 2H, CH2), 7.34 :m, 2H, C6H4,
C6H5), 7.40±7.60 :om, 7H, C6H4, C6H5); IR nmax 2727,
2583, 1497, 1478, 1430, 760, 690 cm21; MS m/z 199
Â
We are grateful to Dr Tamas Martinek for helpful
discussions concerning the NMR assignments and to the