Agric. Biol Chem., 47 (4), 829-838, 1983 829

Stereochemistry and Reactions of Aziridinyl-phosphinothionates Derived from AminoAcids

Akinori Hirashima and Morifusa EtoDepartment of Agricultural Chemistry,Kyushu University, Fukuoka 812, Japan

Received October 1, 1982

Aziridinylphosphinothionates were prepared from optically active ethyl hydrogen phenylphos-phonothionates and l-bromo-2-alkanamines derived from leucine or valine. The aziridine ring wasopened by the action of some nucleophiles. Refluxing the aziridinylphosphinothionates in acetonewith sodium iodide caused hydrolysis accompanied by the rearrangement of the sulfur atom to give

/?-mercaptoethylphosphonamidates. The reaction mechanism was discussed with stereochemicalconsiderations. The insecticidal activity of the products was also examined.

The authors and their coworkers have

found a potent insecticidal activity of 2-meth-oxy-4-alkyl-l,3,2-oxazaphospholidine 2-sul-

fides, i.e. five-membered cyclic phosphorami-dothionates, derived from L-leucine and l-valine.1 ~3) There are four stereoisomers, eachdue to two asymmetric atoms of phosphorusand 4-carbon. An attempt to prepare anal-ogous optically active thiazaphospholidineoxides (8) from j8-bromoethylamines (5) de-

rived from amino acids and chiral phosphono-chloridothionates (2) obtained from resolvedhydrogen phosphonothioates (1) was made.Although a model experiment using diethylphosphonochloridothionate and 3-bromopro-pylamine successfully gave a thiazaphos-phorine derivative (Eq. 1), the attempt to(EtO)2P(S)Cl + BrCH2CH2CH2NH2

0II,

EtO-P' > (1)

prepare 8 was unsuccessful; aziridinylphos-phinothionates (6) were obtained, one of thediastereomers is shown in Fig. 1. This chapterdeals with their streochemistry and reactions.

Formation and reactions of aziridinylphos-

phino thionatesO-Ethyl hydrogen ethyl- and phenyl-

phosphonothioates were resolved via their qui-nine or brucine salts4>5) into the (+)- and (-)-enantiomers. Both the (-)-acids have been

assigned to the (S) configuration by direct X-ray diffraction analysis or chemical correla-

tion.4'^ They were converted into the chlo-rides by the action of phosphorus pentachlo-ride.7) This reaction is known to proceedwith inversion accompanied by a smallamount of racemization. Oxalyl chloride wasmore useful for the chlorination because lessracemization occurred. The optical rotationsand yields of the obtained enantiomers arelisted in Table I.

Optically active l-bromo-2-alkanamine hy-

drobromides (5) were derived from the methylesters (3) of l- and D-leucine and valine by

reduction with sodium borohydride2) into 2-aminoalcohols (4) followed by treatment withhydrobromic acid and phosphorus tri-bromide.8) Their yields and optical rotationsare listed in Table II.

The optically active ethyl phenylphos-phonochloridothionate reacted with enan-tiomeric l -bromo-3-methyl-2-butanamine de-rived from L-valine to give two productswhich were detected on TLC and HPLC(Fig. 2). They were isolated by flash columnchromatography and characterized as thediastereomers of ethyl (2-isopropyl-l-

830 A. Hirashima and M. Eto

aziridinyl)phenylphosphinothionate (6) (R =C6H5; R' = z-C3H7). The (i?)(-)-chloride prep-

aration gave isomers (S)p(S)c and (R)p(S)cof 6 in 77.2 and 22.8% yields, respectively,and the (S)(+)-chloride one gave them in

22.3 and 77.7% yields, respectively, on thebasis of HPLCanalysis. Similar results wereobtained with other bromoamines as shownin Table III. This may be due to the possible

Table I. Ethyl Phosphonochloridothionate(2) from O-Ethyl Hydrogen

Phosphonothioate (1)

1 2

R Con fig- Con fig- Yielduration L(XJd uration [(XJd (%)

(R) +14.8° ($) +48.0° 40

6 5 (5) -14.0° (/?) -47.0° 40

CR) +10.0° (5) +50.0° 332 5 (S) -ll.8° (R) -65.6° 27

optical impurity of the resolved acids or/andracemization in the displacement reactionsat the phosphorus atom, i.e. chlorinationand amidation. At least the major productsshould be twice inverted and the configura-tion assignments were supported by NMRdata; owing to the electron-electron repul-sion between the P = S bonding and anti-nitro-gen lone pair of the aziridine ring and to thefavorable relation between the phosphorusand the alkyl substituent on the aziridine ring,the isopropyl group may be situated closer tothe benzene ring in the (R)p(S)c isomer than inthe (S)p(S)c isomer as shown in the Newmanprojections in Fig. 3 and, consequently, mustbe affected by the diamagnetic anisotropy,consisting of the chemical shift of the methylprotons of <50.46 and 0.78 ppm for (R)P(S)Cand of0.99 and 1.01 ppmfor(S)p(S)c (seeFig. 4).

Figure 5 shows another synthetic route foraziridinylphosphinothionate 6 and its reac-tions. It is possible to suppose that the

PCI.

Et0/P^0H

^-/ -OEtCO2Me

H2N '''R1NaBHt

HBrCH2OHI PBrH2N'R CH2Br+x -

H3N^_''RT

Br^EtO"iH

t 8 S

R Ni..R.

Fig. 1. An Attempt at Thiazaphospholidine Synthesis and Formation of Aziridinylphosphinothionates.

Table II. 1-Bromo-2-alkanammonium Bromides (5) from AminoAcids via 2-Aminoalcohols (4)

4 5

Amino acid Configuration R' V' Id V Id(%) Md (%) Md

Leucine ($) z-QH9 70 + 2.6° 88 + 6.3°(R) /-QH9 76 - 2.6° 95 - 6.7°

Valine (S) i-C3H7 35 + 13.8° 68 + 6.8°(R) V-C3H7 1 5 -25.0° 52 -4.2°

Aziridinylphosphinothionates 831

I

0 8 16 min.

Fig. 2. Separation of Diastereomeric Ethyl (2-Iso-propyl-l-aziridinyl)phenylphosphinothionates by HPLC

on Permaphase ODSEluted with 50% Methanol at 0.22ml/min.

A, (R)P(S)C; B, (S)P(S)C.

bromoalkanaminewasactually converted tothe aziridine prior to reaction with chloride 2.The aziridine ring of 6 was opened by theattack of various nucleophiles. A dithiocar-bamate ion gave dithiocarbamate ester 10; dryhydrogen bromide reacted with 6 to give bro-mide 7 at - 10°C. Furthermore, on heating inacetone in the presence of sodium iodide,aziridinylphosphinothionate 6 gave N-mercaptoethylphosphonamidate 9, probablyvia the iodine analog of 7. Even withoutsodium iodide, refluxing of the acetone so-lution of 6 caused slow conversion of the

aziridine derivative to mercaptan 9, indicatingdirect reaction of the aziridine ring with thethiophosphoryl sulfur group. The mercaptanwas also obtained from 7V-bromoethyl-

phosphonamidothionate 7 and was graduallyconverted to disulflde ll.13C-NMRanalysis of the ring-opened prod-ucts supported that all these ring-opening

Table III. Formation of Aziridinylphosphinothionate Diastereomers 6 (R = C6H5)

Reactants Products 6 (%)

2 5 R ' (R)P(S)C (5)p(5)c CR)P(*)C (S)P(U)C

(/*) (5) z-C4H9 22. 8 77.2(5) (5) /-C4H9 77. 7 22. 3(R) (R) /-QH9 25.4 74. 6OS) (i?) ^-C4H9 7 5. 2 24. 8(R) (S) i-C3H7 22. 5 77. 5

(R) (S) /-C3H7 76.5 23.5

Ha ^^^\/HbV i (So

He ^P- >, ^-s

sHa ,

Hc/^P"0 -^S4A P C\ » H S

Fig. 3. Steric Structures of (R)P(S)C- and (S)p(S)c-Ethyl (2-Isopropyl-l-aziridinyl)phenylphosphino-

thionates.

832A. Hirashima and M. Eto

^PHc=20 Hz ^PHa=20 Hz ^PHb=16 HZ

JHcHd=8 Hz JHaHc=6 Hz JHbHc=4 Hz

^HaHb=1HZ

S ^ HeB .p-N^f't A KaHbL OEt 'à"å CHdMe2 1 1 A,\

__/*uu jiL___jilW 1l » 1 1 L L _J J_ )

A

i

6 5 4 . 3 2 1 ppm 0

Fig. 4. Proton NMRof Ethyl (2-Isopropyl-l-aziridinyl)phenylphosphinothionates.A, CR)p(S)c; B, (5)p(5)c.

EtO S EtO S SCSNMeo EtO S ^SCSNMe2

v +h<i-+vA > X i

2 6 10

HBr/ A with orwithout Nal

1-EtO^/S ^-Br EtO ^0 ^SH EtON^0 .S-S. 0^^OEt

7 9 ll

Fig. 5. Another Synthetic Route for Aziridinylphosphinothionates and Their Reactions.

reactions proceeded by N-CH2bond cleavage(not by N-CHRbond cleavage) indicating thatthe SN2 mechanism was more predominantthan the SN1 mechanism under the employedexperimental conditions.

Spectral characteristicsTable IV shows the characteristic NMRandIR spectral data of amines derived from l-leucine and of the products. The NMRdata of1-methylene and 2-methine, which have toform the aziridine ring, are characteristic on

Aziridinylphosphinothionates 833

Table IV. Spectral Characteristics of Some Products (R=C6H5; R' = j-C4H9)

^-NMR 13C-NMRCompound 31P-NMR IR

CH CH2 CH CH2

4 2.9 (m) 3.5 (q) 50.608 66.401 3500-3200 (OH)3.2(t)

5 3.5-3.9 (m) 51.195 32.995 3400 (NH)6 1.5-2.9 (m) 36.341 31.351 99.027* 810-680 (P=S)

97.609*7 3.2-3.6 (m) 48.847 44.502 810-680 (P=S)

3200(NH)

9 3.4 (m) 2.6 (q) 49.316 31.762 21.257 1220 (P=O), 32002.9 (t) 3400 (NH)

ll 3.2-3.6 (m) 50.197 41.449 3200 (NH)

R =z-C3H7.

comparison amongthe starting materials andthe products. The 2-aminoalcohol (4) gave

complicated proton NMRsignals between 2.9and 3.5 ppm, which shifted to a lower mag-netic field on bromination (5). After the re-action with ethyl phenylphosphonochlorido-thionate, the chemical shift of these protonsmoved to a high field, suggesting ring-closuregiving aziridine (6). This is clearly indicated

by the 13C-NMRdata, too. The 13C signal ofthe 1-methylene at a low field (66 ppm) inthe 2-aminoalcohol (4) was shifted to 33 ppmby bromination, whereas that of the methinecarbon connected with the amino group waschanged little by the reaction. However, theproduct (6) of the reaction with the phos-phonochloridothionate showed the signals ofboth the carbons at a higher field, owing tostraining of the three-membered ring.The aziridinyl derivative gave a bromide (7)with the action of hydrogen bromide showing13C signals of both the carbons at a lower field;the chemical shift of BrCH2 is at a con-

siderably lower field than expected from thesubstitution effect of bromine, probably due tothe deshielding effect of the P= S group. If thering-opening occurred through the SN1 coursegiving a secondary bromide (7'), the expectedchemical shift values of both the methyleneand methine carbons are muchmore deviatedfrom the observed values. This is the case formercaptan 9, too.

EtO S Br\ # *

P CH-iBu/ \ «

Ph NH-CH 2

7'

Mercaptan 9 produced from bromide 7 ordirectly from aziridine 6 shows the 13C chemi-cal shift of methylene as expected as CH2SH.31P-NMR and IR spectrometries confirmedthe conversion of the P=S group into theP=Ogroup in the course of the mercaptanformation. The structure of mercaptan 9 isfurther supported by the mass spectrum (Fig.6), in which the fragment ion M+-CH2SH(m/z 254) gives the base peak.

Stereochemistry and reaction mechanismsThe absolute phosphorus configuration of

ethyl phenylphosphoramidate 9p derived from(S)(-)-ethyl hydrogen phenylphosphono-

thioate lp was determined by chemical cor-relation. The acid catalyzed methanolysis of 9pafforded ( - )-ethyl methyl phenylphosphonate12 in a 75% yield, whose absolute configu-ration has been established as (R).9) This dis-placement reaction occurs with inversion ofthe configuration of phosphorus.10) Thus, thephosphorus configuration of 9p should be (R)as shown in Fig. 7. Twoother stereochemicalcourses of the reactions utilized in this studyhave been established; both the chlorination of

834 A. Hirashima and M. Eto

(*)100

50-

27

2943254

77

Ph+77(93%)iBu

\ 254(100%)

Ph-P-OH j141(36%)

ill100200Ph{?HSL1+N/Ps A'

EtO NH tBu301(M^ trace)

301(P)

m/z 300

Fig. 6. Mass Spectrum of (9-Ethyl A^-(l-Mercapto-4-methylpent-2-yl)phenylphosphonamidate.

PC15

orS (COC1) 2 s

EtO

(S)(-) IPEtO

(*)(-) 2pH2N^'*'-B ft

EtO

(5)p(5)c 6p

M eOH 0 HS,X

H2O

^-~ p 1 «-Me07^0 H+ ^/\N^""R

EtO EtO H

(i?)(-) 12 WpC^c 9p1HBr

S -Br

EtO H(S)p(5)c 7p

Fig. 7. Stereochemistry of Reactions on the Phosphorus Atom.

hydrogen phosphonothioate with phosphoruspentachloride and the amide linkage for-

mation displacing chlorine atoms proceed es-sentially with the inversion of the phosphorus

configuration.7'11} Therefore, it is reasonable

to presume the aziridinylphosphinothionate 6pderived from (£)(-) acid lp has the (S)p

configuration. Since the aziridine ring openingdoes not affect the phosphorus configuration,

the conversion of /?-bromoethylphosphon-amidothionate 7p to jS-mercaptoethylphos-

phonamidate 9p should occur with retention

of the phosphorus configuration as shown inFig. 7.

There are two possible routes for the hy-drolysis of7 to give the mercaptan as shown inFig. 8. In route a, the nucleophilic attack of awater molecule on the phosphorus accom-panied by intramolecular alkylation of thesulfur atom to cause a trigonal bipyramidal(TBP) intermediate maygive the mercaptan bythe following P-S bond cleavage. According tothis route the configuration of the phosphorusmust be inverted. This is not the case for the

Aziridinylpho sphinothionates 835

S HBr S /Br (a) S~"\,..R'II II f .. R-...I /

,p ^ ^r,PN], -/A* >-NH

EtO* ^-R' EtO# H H2° OH

(5)6 \ (S)7 II \A I I,

Nal \ \ (b) *

R-/^NA-R' R-/ H

EtO Na EtO 0

/ 13 (5) 9

/h2o

HO-P-NH ^_ 'P-NH > ^P H

R OEt OEt OEt

14a 14b (*) 9

Fig. 8. Proposed Mechanism for the Hydrolytie Sulfur Rearrangement.

Table V. Physical Properties and Insecticidal Activity of EthylAZIRIDINYLPHOSPHINOTHIONATES (6) (R = C6H5)

Configuration .... , ..R/ _ Yield ral - W24 t t Rfc Mortality %

R p c (%) Md Uu tR Rf (10|ig/fly)

H (R) 71 +2 (1.2) 1.5694 5.4. 0.4 53.8

(S) 54 1.5712 5.4 0.4 2.6

i-C3H7 (i?) OS) 63 + 20 (0.7) 1.5418 12.0 0.3 0(S) (S) 78 +3 (1.2) 1.5433 15.2 0.5 0

j-C4H9 (R) (S) 83 + 13 (0.6) 1.5392 23.6 0.51 10.3(S) (S) 83 +4 (0.5) 1.5302 27.2 0.61 7.7

(R) (R) 88 - 5 (0.8) 1.5340 26.8 0.61 -OS) (R) 100 - 14 (1.1) 1.5330 20.0 0.51 -

a InEtOH.

b HPLC, permaphase ODS 2.1mmx0.5m, MeOH-H2O= 1 : 1, 0.22 ml/min.c TLC, benzene-hexane= 1 : 1.

observed reaction. Pseudorotation of the TBPintermediate may give S-/?-aminoethyl phos-

phonothiolate, which was not actually ob-tained.

Another route, b, starts by intramolecularalkylation forming a thiazaphosphole inter-

mediate (13) followed by the attack of watergiving TBP 14a. A similar thiazaphosphole

intermediate has been proposed for the mech-anism of formation of an SH-compoundbythe acid-catalyzed hydrolysis of thio-TEPA[tris-(l-aziridinyl)phosphine sulfide].12) Be-

cause of the greater apicophilicity of thesulfur atom than that of nitrogen,13) the TBPintermediate (14a) may undergo pseudoro-tation to cause P-S bond cleavage through

836 A. Hirashima and M. Eto

Table VI. Insecticidal Activity ofO-Ethyl 7V-( 1 -Mercapto-2-alkyl)-

phosphonamidates(9)

Con fig- Mortality %uration L Jd at 10//g/fly

C2H5 i-C4H9 (S)p(S)c +35° 97.5(70.3)°(R)P(S)C - 60° 5.0

(S)p(*)c + 45° 52.5(R)P(R)C - 17° 97.5 (97.5)fl

C6H5 z-C3H7 (S)p(S)c 0

WP(5)C + 14° 0/-C4H9 (S)p(S)c - 28° 5.0

(R)P(S)C - 24° 5.0(5)pWc +21° 2.5

(R)P(R\ + 29° 5.0

a Mortality % at 5/zg/fly.

14b. Thus, the phosphorus configuration isretained through the reaction consistent withthe observed result.

Insecticidal activityDiastereomers were separated by flash chro-matography on a silica gel column eluted withfl-hexane. The insecticidal activities of aziridin-ylphosphinothionate 6 and mercaptoalkyl-phosphonamidates 9 were examined againsthousefly (SRS) by topical application. The re-sults are shown in Tables V and VI with theirphysical properties. Phenylphosphonate deriv-atives showed little activity, whereas ethyl-phosphonate derivatives showed some activity.As to the mercaptoalkylphosphonamidates,the insecticidal activity is in the increasingorder of (R)P(S)C, (S)P(R)C, (S)p(S)c and

(R)p(R)c. The difference in insecticidal activitybetween a pair of enantiomers is not significantin comparison with that between diasteTeo-

mers.

EXPERIMENTAL

2-Ethoxy perhydro-1 ,3,2-thiazaphosphorine 2-oxide. To10ml of a 10% alkaline solution of 3-bromopropylaminehydrobromide (0.44 g, 0.002 mol) and a catalytic amountof benzyltriethylammonium chloride (BTEAC) was added

slowly 0,O-diethyl phosphorochloridothionate (0.4g,0.002 mol) in methylene chloride (10 ml). The mixture wasstirred for 1 hr at room temperature. The organic layer waswashed twice with small portions of saturated sodium

chloride solution and then dried over sodium sulfate. Thesolvent was removedunder vacuumand the crude residuewas distilled in a molecular still under high vacuum. Theproduct was obtained in a 88% (0.3g) yield, mp 70~72°C.Found: C, 32.48; H, 6.49; N, 7.25%. Calcd. for

C5H12PO2SN: C, 33.14; H, 6.68; N, 7.74%. ^-NMR

<SSf PPm: 1.3 (3H, t, /=8Hz, OCH2CH3), 1.7 (2H, m,

SCH2CH2CH2NH), 2.6-3.5 (5H, m, NHCH2CH2CH2S),4.05 (2H, m, OCH2CH3). IR vá"I cm"1: 3400, 3200(N-H), 2950, 1420 (C-H), 1215 (P=O), 1050 (P-O-C),560 (P-S).

2-Amino-l-bromo-4-methylpentane hydrobromide (5;

R' = i-C4H9). Leucinol (2-amino-4-methylpentanol) ob-tained from leucine2) was converted to the hydrobromidesalt by treatment with concentrated hydrobromic acid andremoval of water under reduced pressure. The hydrobro-mide (5.3g, 0.03 mol) and 5g (50% excess) of redistilledphosphorus tribromide were placed in a 50ml round-bottomed flask equipped with an extra-long reflux con-denser with an efficientgas-trap attached. The reactionmixture was warmedwith a free flame until the vigorousreaction was complete, the excess phosphorus tribromidewas removed by warming under reduced pressure and thecooled solid residue was washed thoroughly with dry etherand then recrystallized from ethanol. Found: C, 26.98; H,5.88; N, 5.54%. Calcd. for C6H15NBr2: C, 27.61; H, 5.79;N, 5.38%. ^-NMR $££§f ppm: 0.98 (6H, d, /=7Hz,(H3C)2CH), 1.82 (3H, m, Me2CHCH2), 3.50-3.90 (3H,m, BrCH2-CHN), 8.28 (3H, m, NH3+Br"). 13C-NMR

S£53? PPm: 22-016> 22.662 ((H3C)2CH), 24.364 (Me2CH),32.995 (BrCH2CH), 40.158 (CHCH2CHMe2), 51.195(CHNH). (5)-isomer; mp 155~157°C, [ocg0 +6.3° (c=

0.89, EtOH). (i?)-isomer; mp 165- 167°C, [afe° -6.7° (c=2.3, EtOH).

( + )-O-Ethyl phenylphosphonochloridothidnate (2p).(+)-0-Ethyl hydrogen phenylphosphonothioate (0.4g,0.002 mol, [afe° + 14° (c=2.0, i-Pr2O)) dissolved in CC14(10ml) was added dropwise at -5°C to stirred oxalylchloride (0.5g, 0.004 mol) in CC14 (10ml). After the

addition had been completed, stirring was continued for30m at 0°C. After removal of CC14 under reduced pres-sure, the residue was purified by column chromatographyon silica gel using «-hexane as eluent, yielding 0.3 g (68%)of 2p, [a]f>° +95° (c= 1.0, /-Pr2O).

Ethyl (2-isobutyl-l-aziridinyl)phenylphosphinothionate(6; R=C6H5, R'=i-CAH9). To 10ml of a 10% alkalinesolution of 2-amino-l-bromo-4-methylpentane hydro-bromide (5, 0.5g, 0.002 mol) and a catalytic amount ofbenzyltriethylammonium chloride (BTEAC) was addedslowly O-ethyl phenylphosphonochloridothionate (2p;0.4g; 0.002 mol) in methylene chloride (10ml). The mix-ture was stirred for 1 hr at room temperature. The organiclayer was washed twice with small portions of saturatedsodium chloride solution and then dried over sodium

Aziridinylphosphinothionates 837

sulfate. Evaporation of the solvent gave the product whichwas separated by flash column chromatography15) (silicagel, «-hexane) to give the diastereomers (see Table III).Found: C, 58.70; H, 7.79; N, 4.87%. Calcd. forC14H22NOPS: C, 59.34; H, 7.83; N, 4.94%. ^-NMR

£££3i3 PPm: A' Wei 0.65, 0.72 (6H, d, /=7Hz,(H3C)2CH),.1.28 (6H, Me2CHCH2, OCH2CH3, CHMe2),1.80-2.20 (2H, m, NCH2CH), 2.40-2.75 (1H, m,NCH2CH), 3.80-4.30 (2H, m, OCH2CH3), 7.30-8.15(5H, m, PC6H5). B; (S)P(S)C; 1.00 (6H, d, /=7Hz,

(H3C)2CH), 1.29 (5H, Me2CHCH2CH, OCH2CH3),1.40-2.20 (3H, m, NCH2CH, Me2CH), 2.50-2.90 (1H,

m, NCH2CH), 3.80-4.15 (2H, m, OCH2CH3), 7.30-8.15(5H, m, PC6H5). 13C-NMR agggf ppm: 16.027, 16.321 (q,OCH2CH3), 21.605, 23.014 (q, (H3C)2CH), 26.595 (d,

Me2CH), 31.351 (t, NCH2CH), 36.341 (d, NCHCH2),41.038, 41.214 (t, CHCH2CHMe2), 62.350 (t, OCH2CH3),127.810 (P-Ph-/>), 128.341 (P-Ph-m), 131.333 (P-Ph-o),131.746 (P-Ph-x). 31P-NMR ^po34 PPm: (R)P(S)C; 98.576,

(S)p(S)c; 98.392. IR v£eaaxl cm"1: 3050, 2950 (C-H), 1470,1440 (C-H), 1120 (C-N), 1080-1010 (P-O-C), 810-680(P=S). MSm/z: 283(M+; 28.0%), 240(M+ -/Pr; 14.5%),214 [EtOP(SH)PhN=CH2; 100%], 185 [EtOP(S)Ph;99.7%], 157 [PhP(O)SH; 77.0%], 98 (N^-/Bu; 34.1%).

The 2-isopropyl homologue was obtained similarly fromvaline. Found: C, 57.81; H, 7.39; N, 5.01%. Calcd. forC13H20NOPS: C, 57.94; H, 7.48; N, 5.20%. ^-NMR

£££S3 PPm: A; Wp©c; 0.46, 0.78 (6H, d, /=7Hz,

(H3C)2CH), 1.29 (4H, OCH2CH3, CHMe2), 1.70-2.10

(2H, m, NCH2CH), 2.35-2.68 (1H, m, NCH2CH),

3.80-4.30 (2H, m, OCH2CH3), 7.30-8.15 (5H, m,PC6H5). B; (S)p(S)c; 0.99, 1.01 (3H, d, /=5Hz,

(H3C)2CH), 1.25 (3H, t, OCH2CH3), 1.50 (1H, m,

Me2CH), 1.65-2.15 (2H, m, NCH2CH), 2.20-2.63

(1H, m, NCH2CH), 3.80-4.25 (2H, m, OCH2CH3),

7.30-8.15 (5H, m, PC6H5). 31P-NMR d%$?4 ppm: A;(R)P(S)C; 99.027, B; (S)p(S)c; 97.609. MS m/z: 269 (M+;25%), 214 [EtOP(SH)PhN=CH2; 14.6%], 186(EtOPPhSH; 50%), 157 [PhP(O)SH; 62.5%], 84(N^-/Pr; 100%).

Ethyl (2-methyl-l-aziridinyl)phenylphosphinothionate(6; R=C6H5, R'=CHZ). From 0.8g (0.004 mol) of 2p

and 0.2g (0.002 mol) of propyleneimine, 0.95g (99% ofyield) of the object compound was obtained in the waydescribed above. Found: C, 54.88; H, 6.81; N, 5.81%.Calcd. for CnH^NOPS: C, 54.77; H, 6.64; N, 5.81%. XH-NMR dgggf ppm: 1.09, 1.ll, 1.16, 1.19 (3H, d, /=5Hz,

CHCH3), 1.35 (3H, t, /=5Hz, OCH2CH3), 1.5-3.0 (3H,m, CH2CH), 3.8-4.3 (2H, m, OCH2CH3), 7.3-8.2 (5H,m, PC6H5). 13C-NMR5$%i ppm: 16.380 (CH3CH),

17.084 (CH3CH2O), 32.114 (NCH2CH), 32.701(NCHCH2), 62.233 (OCH2CH3), 127.871 (P-Ph-/?),

128.397 (P-Ph-m), 131.098 (P-Ph-o), 131.511 (P-Ph-x). IR

vS? cm"1: 2950, 1460, 1440 (C-H), 1030 (C-N), 1060-

1010 (P-O-C).

Ethyl N-[ l - (N' ,Nf-dimethylthiocarbamoylth io) -4-methylpent-2-yl]phenylphosphonamidothionate (10; R =C6H5, R'=i-C±H9, (RS)p(S)J. A mixture of the cor-

responding aziridine 6 and excess potassium dimethyl-dithiocarbamate in ethanol was refluxed for 7 hr. Work upand column chromatography on silica gel gave 10, Rf(benzene-acetone=l : l) 0.4, [afe° -1° (c= 1.04, EtOH),ni5 1.5956. Found: C, 49.96; H, 7.19; N, 6.91%. Calcd. forC17H29N2OPS3: C, 50.37; H, 7.21; N, 6.91%. ^-NMR<$2$i3 PPm: 0.95 (6H, d, /=7.2Hz, CH(CH3)2), 1.4 (5H,

m, CHCH2CHNH, CH3CH2O), 1.7 (1H, m, Me2CH),

3.2-3.6 (9H, m, N(CH3)2, CH2S2C, CH2CHNH), 4.05(2H, m, OCH2CH3), 7.3-8.1 (5H, m, PC6H5). 13C-NMR<SS3 PPm: 15.910, 16.262 (q, OCH2CH3), 22.662, 22.779

(q, (H3C)2CH), 24.658 (d, Me2CH), 41.449 (t, SCH2),

43.915, 44.091 (t, CH2CHMe2), 45.500, 46.381 (q,(H3C)2N), 61.235, 61.411 (t, OCH2CH3), 128.106 (P-Ph-

p), 128.636 (P-Ph-m), 131.215 (P-Ph-o), 131.568 (P-Ph-*).

IR v^1 cm"1: 3200 (N-H), 2950, 1440 (C-H), 1380

(N-H), 1500, 1250 (C(S)N), 1130 (C-N), 1030 (P-O-C),

820-690 (P=S).

Ethyl N- (l-bromo-4-methylpent-2-yl)phenylphosphon-amidothionate (1; R=C6H5, R/=i-C4.H9). Through

the corresponding aziridine 6 in dry ether, dry hydro-gen bromide prepared from bromine and tetrahydro-naphthalene14) was bubbled at - 10°C. After evapora-tion of ether the residue was dissolved in chloroformand washed twice with a small portion of dilute aqueoussodium carbonate solution and then dried over sodiumsulfate. Evaporation of the solvent and column chroma-tography on silica gave 7. n^ 1.5568. Found: C, 46.97;H, 6.53; N, 3.12%. Calcd. for C14H23NOPSBr: C,46.16; H, 6.36; N, 3.85%. ^-NMR <5ggf ppm: 0.96 (6H,d, .7=6.4Hz, (H3C)2CH), 1.28 (5H, OCH2CH3,NHCHCH2CH), 1.4 (1H, m, CHMe2), 3.2-3.6 (4H, m,

NHCHCH2Br), 4.05 (2H, m, OCH2CH3), 7.3-8.1 (5H,

m, PC6H5). 13C-NMR 5££g? ppm: 16.380 (q, OCH2CH3),22.133, 23.073 (q, (H3C)2CH), 27.006 (d, Me2CH), 41.332(t, NHCHCH2CH), 44.502 (t, NHCHCH2Br), 48.847 (d,NHCHCH2), 62.467 (t, OCH2CH3), 127.871 (d, P-Ph-/?),

128.458 (d, P-Ph-m), 131.159 (d, P-Plw>), 131.568 (s, P-Ph-x). IR v^ax1 cm"1: 3200 (N-H), 3050, 1470, 1440 (C-H),1120 (C-N), 1080-1010 (P-O-C), 820-690 (P=S).

Ethyl N- ( l -mercap to-4-methylpent-2-yl)phenylphos-phonamidate (9; R=C6H5, R'=i-CAH9). The aziridine

(6; R=C6H5, R/=i-C4H9) was refluxed with sodium io-dide in acetone for 7hr. After evaporation of acetonethe residue was dissolved in chloroform and washedtwice with a small portion of saturated sodium chloridesolution and then dried over sodium sulfate. Evapora-tion of the solvent and column chromatography on asilica gave the product. Found: C, 55.47; H, 7.97; N,4.71%. Calcd. for C14H24NO2PS: C, 55.81; H, 7.97; N,4.68%. JH-NMR <$££§f ppm: 0.78, 0.82 (6H, d, /=6Hz,(H3C)2CH), 1.36 (6H, OCH2CH3, NHCHCH2CH, SH),

838 A. Hirashima and M. Eto

1.5-1.8 (1H, m, Me2CH), 2.28 (1H, NH), 2.64, 2.92 (2H,q, t, HSCH2CH), 3.4 (1H, m, CH2CHNH), 4.05 (2H, m,OCH2CH3), 7.3~7.9 (5H, m, PC6H5). 13C-NMR S^hppm: 16.262, 16.556 (q, OCH2CH3), 22.133, 22.838 (q,

(H3C)2CH), 24.482 (d, Me2CH), 31.762 (t, SHCH2),

43.680, 43.915 (t, Me2CHCH2CH), 49.316 (d, CHNH),

60.823 (t, POCH2Me), 128.106 (P-Ph-p), 128.636 (P-Ph-m), 131.215 (P-Ph-o), 131.568 (P-Ph-x). 31P-NMR 8gá"\.ppm: 21.257. IR v££ cm'1: 3400, 3200 (N-H), 2950

(C-H), 1060-1010 (P-O-C), 1220 (P=O). MS m/z: 301(M+; trace), 254 (M+ -CH2SH; 100%), 141 (HO2PPh;36%), 77 (Ph+; 93%).

The disulfide (ll; R=C6H5, R'=i-C4H9). Found: C,

55.89; H, 7.81; N, 4.70%. Calcd. for C28H46N2O4P2S2: C,55.98; H, 7.72; N, 4.66%. ^-NMR $£g§? ppm: 0.78, 0.82(6H, d, J=6.8Hz, CH(CH3)2), 1.3 (5H, OCH2CH3,

CHCH2CHMe), 1.6 (1H, m, CHMe2),2.28 (1H, NH),

2.64, 2.92 (2H, q, t, -SCH2CH), 3.4 (1H, m, CH2CHNH),4.05 (2H, m, OCH2CH3), 7.3-7.9 (5H, m, PC6H5). IRv££ cm"1: 3400, 3200 (N-H), 2950, 1440 (C-H), 1240-

1200 (P=O), 1130 (C-N), 1060-1010 (P-O-C). MS m/z:600 (M+; trace), 254 [M+ -(CH2SSH2C); 94.6%], 186

[PhP(OEt)(OH)NH2; 50.7%], 158 [PhP(OH)2NH2; 100%],

141 [HOP(O)Ph, 79.8%], 94.0 [(MeS)2, 80.4%], 86.0 (2,3-dimethylbutane, 30.5%), 77 (Ph+, 60.8%).

(R)-( - )-O-Ethyl O-methyl phenylphosphonate (\2). Asolution of 9p, (R)P(S)C, [a&0 -24° (0.3g, 0.001 mol) inacidic methanol (1 m H2SO4-MeOH)was stored at roomtemperature for 24 hr and then poured into dilute aqueoussodium carbonate and extracted with chloroform. Thechloroform extract was dried and concentrated.Chromatography of the residue, eluted with ethyl acetate-light petroleum (4: 1), gave 12 (0.15g, 75%), [<x]l° -3.1°(c=1.34, CCI4). ^-NMR <S§3 ppm: 1.32 (3H, t, J=

8.0Hz, POCH2CH3), 3.75 (3H, d, J= 15Hz, POCH3), 4.1(2H, m, POCH2CH3), 7.3-7.9 (5H, m, PC6H5).

Chromatographies. Thin layer chromatography (TLC)

was performed with silica gel G and the following solventsystem: benzene +«-hexane (1 : 1). The phosphonamido-thionates were visualized by spraying 0,5% palladiumchloride in 1 n HC1 or with iodine vapor.

A Shimadzu 830-high performance liquid chromato-

graph (HPLC) was fitted with an ultra-violet photometricdetector and the detection conditions were as follows:Wavelength, 220 nm; chart speed, 2.5 mm/min at a current

of 1 mV; column ODS 2.1 mmx0.5m stainless steel col-umn; mobile phase, methanol-water= 1 : 1; and flow rate;0.22 ml/min.

Other methods. Infrared absorption spectra (IR) wererecorded with a Shimadzu IR-27G spectrophotometer.Mass spectra were obtained with a JEOLmass spec-trometer JMS-01 SG, at 75eV and a D 300 at 70eV. Pro-ton nuclear magnetic resonance spectra, 13C-NMRand31P-NMR were determined on a JEOL JNM-FX100

spectrometer at 100 MHz,100 MHzand 60 MHz,re-spectively. Optical rotations were measured with a HitachiUnion Giken PM-101 polarimeter.

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