JOURNALꢀOFꢀCHEMICALꢀRESEARCHꢀ2008ꢀ 563
insteadꢀofꢀammoniaꢀtoꢀgiveꢀa-hydroxyꢀphosphonatesꢀinsteadꢀ
ofꢀanꢀimineꢀfollowedꢀbyꢀtheꢀadditionꢀofꢀaꢀdiethylꢀphosphiteꢀtoꢀ
formꢀtargetꢀproducts.
H,ꢀ5.61;ꢀN,ꢀ9.70%.
1
2
(
1e): Oil,ꢀ HꢀNMRꢀ(CDCl )ꢀ2.09(br,ꢀ2H,ꢀNH );ꢀ4.18(d,ꢀ1H,ꢀ JPHꢀ
3
2
3
3
=
ꢀ16.0,ꢀCH);ꢀ1.29ꢀ(t,ꢀ3H,ꢀ Jꢀ=ꢀ7.2,ꢀCH );ꢀ1.19(t,ꢀ3H,ꢀ Jꢀ=ꢀ7.2,ꢀCH );ꢀ
3
3
1
3
4
1
1
.11–3.83ꢀ(m,ꢀ4H,ꢀ2CH );ꢀ7.20–6.66ꢀ(m,ꢀ4H,ꢀAr);ꢀ CꢀNMR(CDCl )ꢀ
6.21,ꢀ16.31,ꢀ62.7,ꢀ62.0,ꢀ49.5,ꢀ128.3,ꢀ115.2,ꢀ154.3;ꢀIR(Film,ꢀcm )ꢀ
216ꢀ(Pꢀ=ꢀO),ꢀ1027ꢀ(P–O–Et),ꢀ3193(br,–OH,ꢀ–NH );ꢀAnal.ꢀCalcdꢀforꢀ
2
3
Inꢀ summary,ꢀ aꢀ facileꢀ andꢀ straightforwardꢀ synthesisꢀ ofꢀ a-
aminoꢀ phosphonatesꢀ underꢀ solvent-freeꢀ reactionꢀ conditionsꢀ
isꢀdescribedꢀonꢀanꢀacidicꢀsilicaꢀgelꢀsupportꢀusingꢀanhydrousꢀ
ammoniumꢀacetate,ꢀaromaticꢀaldehydesꢀandꢀdiethylꢀphosphiteꢀ
asꢀ startingꢀ materialsꢀ inꢀ moderateꢀ yields.ꢀ Thisꢀ methodꢀ isꢀ aꢀ
simpleꢀoperation,ꢀandꢀitꢀhasꢀrelativelyꢀfastꢀreactionꢀratesꢀandꢀ
shortꢀreactionꢀtimes.ꢀTheseꢀmakeꢀtheꢀmethodꢀanꢀattractiveꢀandꢀ
usefulꢀcontributionꢀtoꢀpresentꢀsyntheses.
-
1
2
C H NO P: C, 50.96; H, 7.00; N, 5.40. Found: C, 51.21; H, 6.91;
11
18
4
N,ꢀ5.20%.
1f): Oil,ꢀ Hꢀ NMRꢀ (CDCl )ꢀ 2.08(br,ꢀ 2H,ꢀ NH );ꢀ 4.18(d,ꢀ 1H,ꢀ
1
(
3
2
2J ꢀ=ꢀ16.0,ꢀCH);ꢀ3.85ꢀ(s,ꢀ3H,ꢀ–OCH );ꢀ1.29(t,ꢀ3H,ꢀ Jꢀ=ꢀ7.2,ꢀCH );ꢀ
3
PH
3
3
3
1
(
.19ꢀ (t,ꢀ 3H,ꢀ Jꢀ =ꢀ 7.2,ꢀ CH );ꢀ 4.08–3.96ꢀ (m,ꢀ 4H,ꢀ 2CH );ꢀ 7.02–6.83ꢀ
m,ꢀ3H,ꢀAr);ꢀ CꢀNMR(CDCl )ꢀ15.81,ꢀ15.41,ꢀ59.7,ꢀ58.3,ꢀ50.6,ꢀ56.9,ꢀ
3
2
1
3
3
-1
1
29.7,ꢀ120.6,ꢀ112.3,ꢀ115.7,ꢀ146.9,ꢀ148.5;ꢀIR(Film,ꢀcm )ꢀ1218ꢀ(Pꢀ=ꢀO),ꢀ
1
027ꢀ(P–O–Et),ꢀ3184(–OH,ꢀ–NH );ꢀAnal.ꢀCalcdꢀforꢀC H NO P: C,
2
12 20
5
Experimental
49.83; H, 6.97; N, 4.84. Found: C, 49.56; H, 6.81; N, 4.71%.
1
2
(
1g): Oil,ꢀ HꢀNMRꢀ(CDCl )ꢀ2.00ꢀ(br,ꢀ2H,ꢀNH );ꢀ4.20ꢀ(d,ꢀ1H,ꢀ JPHꢀ
3
2
AllꢀmeltingꢀpointsꢀwereꢀdeterminedꢀonꢀaꢀYanacoꢀapparatusꢀandꢀareꢀ
uncorrected.ꢀ NMRꢀ spectraꢀ wereꢀ measuredꢀ onꢀ aꢀ Brukerꢀ 400ꢀ NMRꢀ
instrumentꢀ inꢀ CDCl ꢀ andꢀ chemicalꢀ shiftsꢀ areꢀ expressedꢀ asꢀ dꢀ units,ꢀ
TMSꢀ wasꢀ usedꢀ asꢀ anꢀ internalꢀ standardꢀ forꢀ Hꢀ NMR,ꢀ Cꢀ NMR.ꢀ
IR spectra were determined as liquid films on Avatar360FT-IR
spectrophotometer.
3
=
(
ꢀ16.4,ꢀCH);ꢀ3.79ꢀ(s,ꢀ3H,ꢀ–OCH );ꢀ1.28ꢀ(t,ꢀ3H,ꢀ Jꢀ=ꢀ7.2,ꢀCH );ꢀ1.18ꢀ
t,ꢀ3H,ꢀ Jꢀ=ꢀ7.2,ꢀCH );ꢀ4.08–3.87ꢀ(m,ꢀ4H,ꢀ2CH );ꢀ7.38–6.87ꢀ(m,ꢀ4H,ꢀ
Ar);ꢀ CꢀNMR(CDCl3)ꢀ16.21,ꢀ16.31,ꢀ62.7,ꢀ62.0,ꢀ49.7,ꢀ55.8,ꢀ128.4,ꢀ
58.6,ꢀ127.2,ꢀ114.3;ꢀIR(Film,ꢀcm )ꢀ1249ꢀ(Pꢀ=ꢀO),ꢀ1023ꢀ(P–O–Et),ꢀ
458ꢀ(–NH );ꢀAnal.ꢀCalcdꢀforꢀC H NO P: C, 52.74; H, 7.38; N,
.13. Found: C, 52.76; H, 7.21; N, 5.21%.
3
3
3
3
2
3
13
1
13
-1
1
3
5
2
12 20
4
ElementalꢀanalysisꢀwasꢀcarriedꢀoutꢀwithꢀaꢀYanacoꢀCHNcorderꢀMT-
ꢀAnalyser.ꢀAllꢀaldehydesꢀwereꢀredistilledꢀbeforeꢀbeingꢀused.
1
2
(1h): Oil,ꢀ HꢀNMRꢀ(CDCl )ꢀ2.01(br,ꢀ2H,ꢀNH );ꢀ4.15ꢀ(d,ꢀ1H,ꢀ JPHꢀ
3
2
3
=
ꢀ 16.0,ꢀ CH);ꢀ 2.93ꢀ (s,ꢀ 6H,ꢀ –N(CH ) );ꢀ 1.30–1.12ꢀ (m,ꢀ 6H,ꢀ 2CH );ꢀ
3
2
3
1
3
4
.11–3.95ꢀ(m,ꢀ4H,ꢀ2CH );ꢀ7.31–6.63ꢀ(m,ꢀ4H,ꢀAr);ꢀ CꢀNMR(CDCl )ꢀ
2
3
General method
1
4.8,ꢀ14.0,ꢀ58.3,ꢀ59.1,ꢀ49.8,ꢀ40.4,ꢀ125.5ꢀ154.4,ꢀ112.2,ꢀ127.0;ꢀIR(Film,ꢀ
Toꢀtheꢀmixtureꢀofꢀanhydrousꢀammoniumꢀacetate 2ꢀ(0.037ꢀmol)ꢀandꢀ
chromatographyꢀ silicaꢀ gelꢀ (2ꢀ g)ꢀ wasꢀ addedꢀ aromaticꢀ aldehydesꢀ 4ꢀ
-1
cm )ꢀ1240ꢀ(Pꢀ=ꢀO),ꢀ1027ꢀ(P–O–Et),ꢀ3457ꢀ(–NH );ꢀAnal.ꢀCalcdꢀforꢀ
2
C H N O P: C, 54.54; H, 8.10; N, 9.78. Found: C, 54.46; H, 8.21;
1
3
23
2
3
(0.025ꢀmol),ꢀthenꢀdiethylꢀphosphiteꢀ3 (0.025ꢀmol)ꢀwasꢀaddedꢀwithꢀ
N,ꢀ9.51%.
vigorousꢀstirring.ꢀAfterꢀtheꢀcompletionꢀofꢀtheꢀaddition,ꢀtheꢀreactionꢀ
mixtureꢀisꢀsmoothlyꢀheatedꢀatꢀ50–60ꢀ°Cꢀforꢀ1–2ꢀh.ꢀandꢀthenꢀallowedꢀtoꢀ
coolꢀtoꢀroomꢀtemperature.ꢀTheꢀresultingꢀreactionꢀmixtureꢀisꢀextractedꢀ
withꢀdichloromethane(2ꢀ¥ꢀ25ꢀml).ꢀEvaporationꢀofꢀtheꢀsolventꢀgaveꢀtheꢀ
crude product. The product was purified by column chromatography
onꢀ silicaꢀ gelꢀ usingꢀ aꢀ mixtureꢀ ofꢀ ethylacetateꢀ andꢀ hexaneꢀ asꢀ eluentꢀ
1
(
3
2
3
3
Jꢀ=ꢀ3.2,ꢀfurfuryl);ꢀ1.32(t,ꢀ3H,ꢀ Jꢀ=ꢀ6.8,ꢀCH );ꢀ1.25ꢀ(t,ꢀ3H,ꢀ Jꢀ=ꢀ6.8,ꢀ
3
3
3
1
3
CH );ꢀ4.15–3.99(m,ꢀ4H,ꢀ2CH );ꢀ CꢀNMR(CDCl )ꢀ16.3,ꢀ16.0,ꢀ60.3,ꢀ
3
2
3
-1
6
1
(
10:90) to give oil liquid compounds 1.
2
1
2
(1a): Oil, HꢀNMRꢀ(CDCl )ꢀ2.74ꢀ(br,ꢀ2H,ꢀNH );ꢀ4.22ꢀ(d,ꢀ1H,ꢀ JPHꢀ
3
2
=
ꢀ17.2,ꢀCH);ꢀ1.27–1.13ꢀ(m,ꢀ6H,ꢀ2CH );ꢀ4.04–3.82ꢀ(m,ꢀ4H,ꢀ2CH );ꢀ
3
2
.48–7.27ꢀ(m,ꢀ5H,ꢀAr);ꢀ13CꢀNMR(CDCl )ꢀ16.11,ꢀ16.32,ꢀ62.7,ꢀ62.9,ꢀ
Received 17 June 2008; accepted 31 July 2008
Paper 08/5332 doi: 10.3184/030823408X349998
Published online: 8 October 2008
7
4
3
-1
9.5,ꢀ128.3,ꢀ136.7,ꢀ126.7;ꢀIR(Film,ꢀcm )ꢀ1241ꢀ(Pꢀ=ꢀO),ꢀ1028ꢀ(P–O–
Et),ꢀ3383ꢀ(NH );ꢀAnal.ꢀCalcdꢀforꢀC H NO P: C, 54.32; H, 7.46; N,
2
11 18
3
5
.76. Found: C, 54.37; H, 7.61; N, 5.42%.
1
2
(
1b): Oil,ꢀ HꢀNMRꢀ(CDCl )ꢀ1.97(br,ꢀ2H,ꢀNH );ꢀ4.24ꢀ(d,ꢀ1H,ꢀ J
3 2 PHꢀ
3
3
References
=
ꢀ17.2,ꢀCH);ꢀ1.28ꢀ(t,ꢀ3H,ꢀ Jꢀ=ꢀ7.2,ꢀCH );ꢀ1.21ꢀ(t,ꢀ3H,ꢀ Jꢀ=ꢀ7.2,ꢀCH );ꢀ
3
3
1
3
ꢀ 2ꢀ R.ꢀEngel,ꢀChem. Rev.,ꢀ1977,ꢀ77,ꢀ349.
4
1
1
.09–3.89ꢀ(m,ꢀ4H,ꢀ2CH );ꢀ7.41–7.28(m,ꢀ4H,ꢀAr);ꢀ CꢀNMR(CDCl )ꢀ
6.21, 16.32, 62.4, 62.6, 49.5, 128.5, 134.7, 130.7; IR(film, cm )ꢀ
240ꢀ (Pꢀ =ꢀ O),ꢀ 1026ꢀ (P–O–Et),ꢀ 3376ꢀ (–NH );ꢀ Anal.ꢀ Calcdꢀ forꢀ
2
3
-
1
ꢀ
ꢀ
ꢀ
ꢀ
3ꢀ J.ꢀHiratakeꢀandꢀJ.ꢀOda,ꢀBiosci. Biotechnol. Biochem.,ꢀ1997,ꢀ61,ꢀ211.
4ꢀ K.A.ꢀSchugꢀandꢀW.ꢀLindner,ꢀChem. Rev.,ꢀ2005,ꢀ105,ꢀ64.
acids,ꢀJohnꢀWileyꢀ&ꢀSons,ꢀChichester,ꢀ2000.
2
C H ClNO P: C, 47.58; H, 6.17; N, 5.04. Found: C, 47.36; H, 6.21;
N,ꢀ5.10%.
1c): Oil,ꢀ HꢀNMRꢀ(CDCl )ꢀ1.98ꢀ(br,ꢀ2H,ꢀNH );ꢀ4.77ꢀ(d,ꢀ1H,ꢀ JPHꢀ
11
17
3
1
2
(
3
2
=
ꢀ 18.4,ꢀ CH);ꢀ 1.34–1.15ꢀ(m,ꢀ6H,ꢀ2CH );ꢀ4.18–3.87ꢀ(m,ꢀ4H,ꢀ2CH );ꢀ
ꢀ 7ꢀ S.ꢀBhagatꢀandꢀA.K.ꢀChakraboorti,ꢀJ. Org. Chem.,ꢀ2007,ꢀ72,ꢀ3158.
ꢀ 8ꢀ S.ꢀ Chandrasekhar,ꢀ S.J.ꢀ Prakash,ꢀ V.ꢀ Jagadeshwarꢀ andꢀ C.ꢀ Narsihmulu,ꢀ
Tetrahedron Lett.,ꢀ2001,ꢀ42,ꢀ5561.ꢀ
3
2
7
4
.63–7.29ꢀ(m,ꢀ3H,ꢀAr);ꢀ13CꢀNMR(CDCl )ꢀ16.52,ꢀ16.41,ꢀ60.7,ꢀ61.5,ꢀ
3
-1
4.5,ꢀ140.5,ꢀ129.7,ꢀ126.2,ꢀ133.2,ꢀ130.1,ꢀ133.1;ꢀIR(Film,ꢀcm )ꢀ1241ꢀ
ꢀ
9ꢀ S.ꢀKudrimotiꢀandꢀV.R.ꢀBommena,ꢀTetrahedron Lett., 2005,ꢀ46,ꢀ1209.
(Pꢀ=ꢀO),ꢀ1031ꢀ(P–O–Et),ꢀ3384ꢀ(–NH ); ꢀA nal.ꢀCalcdꢀforꢀC H Cl NO P:
2 11 16 2 3
ꢀ10ꢀ M.E.ꢀChalmersꢀandꢀG.M.ꢀKosolapoff,ꢀJ. Am. Chem. Soc.,ꢀ1953,ꢀ75,ꢀ5278.
C, 42.33; H, 5.17; N, 4.49. Found: C, 42.36; H, 5.31; N, 4.70%.
1
2
ꢀ11ꢀ H.ꢀ Takahashi,ꢀ M.ꢀ Yoshioka,ꢀ N.ꢀ Imai,ꢀ K.ꢀ Onimuraꢀ andꢀ S.ꢀ Kobayashi,ꢀ
(
1d): Oil,ꢀ HꢀNMRꢀ(CDCl )ꢀ2.25ꢀ(br,ꢀ2H,ꢀNH );ꢀ4.44ꢀ(d,ꢀ1H,ꢀ JPHꢀ
3
2
Synthesis,ꢀ1994,ꢀ763.
=
ꢀ18.0,ꢀCH);ꢀ1.28–1.25ꢀ(m,ꢀ6H,ꢀ2CH );ꢀ4.11–4.07ꢀ(m,ꢀ4H,ꢀ2CH );ꢀ
3
2
ꢀ
12ꢀ J.ꢀOlcksyszyn,ꢀL.ꢀSubotkowskaꢀandꢀP.ꢀMastalerz,ꢀSynthesis, 1979,ꢀ985.
ꢀ13ꢀ B.ꢀKaboudinꢀandꢀR.ꢀNazariꢀTetrahedron Lett., 2001,ꢀ42,ꢀ8211.
14ꢀ B.ꢀKaboudinꢀandꢀK.ꢀMoradi,ꢀTetrahedron Lett.,ꢀ2005,ꢀ46,ꢀ2989.
8
4
.37–7.52ꢀ(m,ꢀ4H,ꢀAr);ꢀ13CꢀNMR(CDCl )ꢀ16.51,ꢀ16.31,ꢀ62.7,ꢀ61.5,ꢀ
3
-1
8.5,ꢀ147.3,ꢀ137.0,ꢀ134.3,ꢀ123.3,ꢀ129.6,ꢀ121.9;ꢀIR(Film,ꢀcm )ꢀ1244ꢀ
ꢀ
(Pꢀ =ꢀ O),ꢀ 1027ꢀ (P–O–Et),ꢀ 3277ꢀ (–NH ),ꢀ 1531,ꢀ 1362ꢀ (–NO );ꢀAnal.ꢀ
ꢀ15ꢀ H.ꢀ Takahashi,ꢀ M.ꢀ Yoshioka,ꢀ N.ꢀ Imai,ꢀ K.ꢀ Onimuraꢀ andꢀ S.ꢀ Kobayashiꢀ
2
2
CalcdꢀforꢀC H N O P: C, 45.84; H, 5.94; N, 9.72. Found: C, 45.66;
Synthesis,ꢀ1994,ꢀ763.
11
17
2
5