1882
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009
Bondarenko et al.
3
(53.6%) of 2ꢀmethoxyethylamine, b.p. 94—96 °C. 1H NMR
(CDCl3), δ: 1.44 (s, 2 H, NH2); 2.72 (t, 2 H, NCH2, 3JH,H = 5.2 Hz);
3.24 (s, 3 H, OMe); 3.28 (t, 2 H, CH2O, JH,H = 5.2 Hz).
Published data:35 b.p. 95 °C.
NMe2, JH,P = 11.0 Hz); 7.40—7.51 (m, 6 H, Ph); 7.79—7.88
(m, 4 H, Ph).
3
Diphenylphosphinic (2ꢀhydroxyethyl)methylamide (3b) was
prepared by method B from Nꢀ(2ꢀhydroxyethyl)methylamine
(1.2 g, 16.0 mmol), CCl4 (2.5 mL, 24.0 mmol), a 30% aqueous
solution of NaOH (0.4 g, 9.0 mmol), and diphenylphosphinous
acid (1.7 g, 8.0 mmol). After workup of the reaction mixture, the
residue contained, according to 1H and 31P NMR data, 1.9 g
(82 %) of amide 3b (δ 34.0) and 0.4 g (18%) of Oꢀ[2ꢀ(Nꢀdiꢀ
phenylphosphinylꢀNꢀmethyl)amino]ethyl] diphenylphosphinate
Ph2P(O)N(Me)CH2CH2OP(O)Ph2 (δ 32.0 (P—N) and 32.7
(P—O)). After three recrystallizations from a hexane—EtOAc
mixture, the yield of amide 3b was 1.0 g (43.5%), m.p. 108.5—
109.5 °C. 31P NMR (CDCl3), δ: 34.2. 1H NMR (CDCl3), δ:
2.72 (d, 3 H, NMe, JH,P = 10.7 Hz); 3.18—3.43 (m, 2 H,
NCH2 + OH); 3.75 (t, 2 H, CH2O, 3JH,H = 4.3 Hz); 7.42—7.74
(m, 6 H, Ph); 7.79—8.12 (m, 4 H, Ph).
Phosphorylation of primary amines, dimethylamine, and
Nꢀ(2ꢀhydroxyethyl)ꢀNꢀmethylamine. Diethylphosphoric and diarylꢀ
and dibutylphosphinic alkylꢀ and dialkylamides 2a—n and 3a—c
(general procedures). Method А. A 27% aqueous solution of
methylamine (15 mmol) and a 50% aqueous solution of NaOH
(11 mmol) were successively added dropwise at 0—5 °C to a
stirred solution of acid 1 (10 mmol) in CH2Cl2 (10 mL) and
CCl4 (30 mmol). The reaction mixture was stirred at 20—25 °C
for 0.5—1 h, the organic layer was separated, washed with a
saturated solution of K2CO3 (2×5 mL) and water (3×5 mL),
dried with Na2SO4, and concentrated in vacuo. The residue was
distilled, recrystallized or chromatographed on silica gel (see
Tables 1 and 2).
P
P
3
Method B. A solution of acid 1 (5—12 mmol) in CH2Cl2
(5 mL) was added dropwise at 0—5 °C to a stirred mixture of
amine (10 mmol), CCl4 (30 mmol), CH2Cl2 (5 mL), and a
solution of NaOH (13 mmol) in water (1.5 mL). The reaction
mixture was stirred and workedꢀup as in method А. The residue
was recrystallized (see Tables 1 and 2).
Method C. A 30% aqueous solution of NaOH (23 mmol)
was added dropwise at 0—5 °C to a stirred mixture of acid 1
(10 mmol), amine hydrochloride (15 mmol), CCl4 (30 mmol),
and CH2Cl2 (10 mL). After stirring and workup of the reaction
mixture as in method А, the residue was recrystallized (see
Tables 1 and 2).
Dibutylphosphinic dimethylamide (3c) was prepared by
method А from dibutylphosphinous acid (1.6 g, 9.8 mmol), CCl4
(2.8 mL, 29.4 mmol), a 38% aqueous solution of dimethylamine
(0.9 g, 16.3 mmol), and 50% aqueous solution of NaOH (0.5 g,
10.7 mmol) as an oil. After chromatography on a silica gel
column in a CHCl3—MeOH system (10 : 1), the yield of amide
3c was 1.2 g (60%). 31P NMR (CDCl3), δ: 50.2. 1H NMR
(CDCl3), δ: 0.93 (t, 3 H, Me, JH,H = 7.1 Hz); 1.33—1.77 (m,
12 H, PCH2CH2CH2Me); 2.65 (d, 6 H, NMe2, JH,P = 9.2 Hz).
Alkylation of diethyl Nꢀmethylphosphoramidate (2a) with butyl
bromide. А (in the presence of aqueous alkali). A 50% aqueous
solution of NaOH (2.1 g, 53.9 mmol) was added at 20 °C to a
stirred solution of amide 2a (4.5 g, 26.9 mmol) and Bu4NBr
(0.4 g, 1.3 mmol) in toluene (10 mL). Then BuBr (4.6 g,
33.6 mmol) was added dropwise, and the mixture was heated for
4 h at 75—80 °C. The organic layer was separated, washed with
water (3Ѕ5 mL), dried with Na2SO4, and concentrated in vacuo
to give 1.1 g (16%) of diethyl NꢀbutylꢀNꢀmethylphosphoramidate
(4). 31P NMR (CDCl3): δ 10.6. 1H NMR (CDCl3), δ: 0.89 (t,
Diphenylphosphinic (2ꢀhydroxyethyl)amide (2h) was synꢀ
thesized by method B from 2ꢀhydroxyethylamine (1.2 g, 20 mmol),
CCl4 (3 mL, 30 mmol), a 30% aqueous solution of NaOH (0.4 g,
13 mmol), and diphenylphosphinous acid (2.0 g, 10 mmol).
After workup of the reaction mixture as in method А, the residue
1
contained, according to H and 31P NMR data, 2.5 g (95%) of
amide 2h (δP 26.6) and 0.1 g (5%) of Oꢀ[2ꢀ(diphenylphosphinylꢀ
amino)ethyl] diphenylphosphinate Ph2P(O)NHCH2CH2Oꢀ
3
3 H, N(CH2)3CH3, JH,H = 7.2 Hz); 1.22—1.35 (m, 8 H,
P(O)Ph2 (δ 24.6 (P—N) and 33.6 (P—O)). After two recrysꢀ
tallizations from EtOAc, the yield of amide 2h was 2.0 g (77%)
(see Table 1, 2).
Diphenylphosphinic (3ꢀhydroxypropyl)amide (2i) was synꢀ
thesized by method B from 3ꢀhydroxypropylamine (2.2 g,
29.0 mmol), CCl4 (4.2 mL, 43.5 mmol), 30% aqueous solution
of NaOH (0.6 g, 15.9 mmol), and diphenylphosphinous acid
(2.9 g, 14.5 mmol). After workup of the reaction mixture, the
residue contained, according to 1H and 31P NMR data, 3.9 g
OCH2CH3 + NCH2CH2CH2); 1.41—1.52 (m, 2 H, NCH2CH2);
2.61 (δ, 3 H, NMe, 3JH,P = 9.9 Hz); 2.91—2.99 (m, 2 H, NCH2);
3.88—4.08 (m, 4 H, OCH2). The aqueous layer of the reaction
mixture contains sodium Oꢀethyl Nꢀmethylphosphoramidate (5).
31P NMR (D2O), δ: 10.9. 1H NMR (D2O), δ: 1.18 (t, 3 H,
P
3
3
Me, JH,H = 7.0 Hz); 2.39 (d, 3 H, NMe, JH,P = 12.8 Hz);
3.75—4.85 (m, 4 H, OCH2).
В (in the presence of solid alkali). A powdered mixture
of NaOH (2.2 g, 53.8 mmol) and anhydrous K2CO3 (7.4 g,
53.8 mmol) was added at 20 °C to a stirred solution of amide 2a
(4.5 g, 26.9 mmol) in CH2Cl2 (10 mL). Then BuBr (4.6 g,
33.6 mmol) was added dropwise and the mixture was heated for
3 h at 40—45 °C. The precipitate was filtered off, the filtrate was
(97%) of amide 2i (δ 25.6) and 0.1 g (3%) of Oꢀ[3ꢀ(diphenylꢀ
P
phosphinylamino)propyl] diphenylphosphinate Ph2P(O)NHꢀ
CH2CH2CH2OP(O)Ph2 (δ 24.4 (P—N) and 32.9 (P—O)). After
P
two recrystallizations from a EtOAc—MeOH mixture, the yield
of amide 2i was 3.6 g (90%) (see Tables 1 and 2).
1
concentrated. According to H and 31P NMR data, the residue
Diphenylphosphinic dimethylamide (3a) was prepared by
method А from diphenylphosphinous acid (1.7 g, 8.2 mmol),
CCl4 (2.4 mL, 24.5 mmol), 38% aqueous solution of dimethylꢀ
amine (0.7 g, 16.3 mmol), and 50% aqueous solution of NaOH
(0.4 g, 9.0 mmol). From the organic layer, 1.7 g (85%) of the
product was isolated, m.p. 101—103 °C. After recrystallization
from a hexane—benzene mixture, the yield of amide 3a was 1.6 g
(80%), m.p. 103—105 °C (Published data:36 m.p. 103—105 °C).
31P NMR (CDCl3), δ: 31.4. 1H NMR (CDCl3), δ: 2.64 (d, 6 H,
contained 2.8 g (47%) of diethyl NꢀbutylꢀNꢀmethylphosꢀ
phoramidate (4) (δ 10.7) and 2.5 g (48%) of Oꢀbutyl Oꢀethyl
P
Nꢀmethylphosphoramidate (6) (δ 10.4). 1H NMR (CDCl3), δ:
P
0.89 (t, 3 H, N(CH2)3CH3 (4), 3JH,H = 7.2 Hz); 1.12—1.40 (m,
18 H, OCH2CH3 + NCH2CH2CH2 (4) and OCH2CH3
+
OCH2CH2CH2CH3 (6)); 1.41—1.58 (m, 2 H, NCH2CH2 (4));
2.56 (dd, 3 H, NMe, 3JH,P = 12.1 Hz, 3JH,H = 6.4 Hz (6)); 2.61
(d, 3 H, NMe, 3JH,P = 10.0 Hz (4)); 2.91—3.08 (m, 3 H, NCH2
(4) + NH (6)); 3.90—4.13 (m, 8 H, OCH2 (4) + OCH2 (6)).