1598 CHINESE JOURNAL OF CHEMISIRY Unn, 20, 1598-1601

Synthesis, Mechanism of Formation and Insecticidal Activity of Novel Fluorinated Organophosphorus Compounds

WU, Jun'*"(%%) IIUDSON, HarrgR.' 'Department ofchemisny, Z h e j m g Univers*, Hangzhou, ,Zhqumg 310027, China Division of Chemistry, School of Bwbgicul and Applied sciences, University of North London, London N7 8DB, UK

Introduction

Organophosphorus cornpounds are widely used as in- secticides, herbicides and fungcides. In view of the pos- sible influence of fluorine substitution on the biological activity of organophosphorus compounds we have turned our attention to the study of the synthesis and biological activity of fluorinated organophosphorus compounds.

In the c o w of investigation on the fungicidal activ- ity of guanidine derivatives, including the N-( o-guanidi- noallryl) arninoakmephosphonic acids and their amino-

phosphonic pl.ecursors, Hudson et ul . found that certain members of the a-aminoalkan ephosphonic acids showed the best activity and were patented as agricultural fuqg- cides, especially as seed-dressing agents. ' Of these com- poundes, a-aminopropanephosphonic acid is the most ac- tive and is now listed under the name ampropylfos as an available alternative to organomercury compounds for the

contml of covered smut, loose smut in oats.2 ~n view of the influence of fluorine substitution on the fuqgcidal ac- tivity of a-aminoalkanephosphonic acid, we attempted the p r e p t i o n of fluorinated a-aminopropanephosphonic acid via diethyl 3-fluompropanoylphosphonate (Scheme 1, R' = Et, R2 = FCH2CH2) (2) . 3 ?he latter was a key inter- mediate in the formation of the componding oxime and thence, by reduction and hydroly-sis, fluorinated a - aminopropanephosphonic acid. Examination of the total initial products obtained from triethyl phosphite and 3-flu- oropropanoyl chloride showed, however, that the major components of the mixture were diethyl ( E ) - 1-( 3-fluom- propanoyloxy ) -3-fluo~pmp- 1 -enylphosphonate ( 3 ) and diethyl 1 - ( diethoxyphosphoryl ) -3-fluoropropyl phosphate (4) .

In this paper, the preparation, mechanism, spec- truscopy and insecticidal activity of novel fluorinated organophosphorus compounds obtained from the interaction between triethyl phosphite and 3-fluoropropanoyl chloride am n3ported.

scheme1

(R'O)$' + R'COCl - (R'O),P(0)COR2 + R'CI 1 2

Results and discusion

Preparation of organophosphorus compowuis 3 and 4

Trialkyl phosphites enter readily into the Michaelis-

* Ed: Wujumvu@hotmail.com Received February 4, 2OU2; revised June 17, u102; accepted August 2, 2002. Roject supported by the SinBritish Friendship Schohh ip Scheme.

Vol. 20 No. 12 2002 Chinese Journal of Chemisby 1599

A k n u ~ v reaction with acyl chlorides (1) at mom tempera- ture or below, to give the corresponding dialkyl acylphos- phonates ( Scheme 1 (2 ) .4,5 Examination of the total initial products obtained from triethyl phosphite and 3-flu- oropmpanoyl chloride by 3' P NMR spectroscopy showed, however, that the major components of the mixture ( ca . 25 m l % of each) were the reaction products (Scheme 2)

ethyl 3-fluompmpanoylphosphonate ( 5 ) ( 6 p - 2.9) was also present ( c a . u) mol%), together with minor amounts ( a. 3-5 mol% ) of triethyl phosphate ( 6 p

- 3.01, diethyl phosphite ( 6 p 7 .9) and a further by- product ( 8 p 19.81, which is tentatively assigned as a- hydrcacy-l,l-bis( phosphonate) (6) . Other ( unidentified amounted up to ca . 15%) phosphorus-containing com- pounds were also present. The initial products were com- plicated and the volatile by-products were k t l y removed at reduced pressure and then the residue was subjected to column chromatography to give 3 and 4.

3 ( 6 ~ 7 . 2 ) and 4 (6p 19.7, -0.6, J p p u ) HZ). Di-

3 4

5 6

Characteridon of organophosphorus cornpounds 3 and 4

'H and 13C NMR data for both 3 and 4 are described in the experimental section. 'Ihe 31 P NMR chemical shifts am for3 (6p7.9) and4 ( 6 ~ 1 9 . 7 , -0.6, J , 2 O H Z ) . "F NMR signals appear at 6 - 52.36, - 56.72 for 3, and 6 - 54.93 for 4. Assignment of ( E ) -stemhemistry to the product 3 can be made on the basis of the magni- tude of the coupling observed between phosphorus and the &-related vinylic proton ( 3 J ~ cu. 11 HZ), which is within the range established for cis-coupling in vinylphos- phonates ( J ~ H 10-30 Hz) . A considerably hiher val- ue ( 3 J m 30-50 Hz) would be expected if the phospho- rus and vinylic proton bore a tmw-relationship to each other.6 Further confirmation of ( E)-confiption in the

product 3 is given by the magnitude of couphng between the allylic fluorine atom and phosphorus ( 4JpF ca . 1 Hz), which is similar to that in other related phospho- nates.' None of the ( Z )-isomer was detectable by NMR Spec-PY *

'Ihe positive-ion fast atom bombardment mass spectra of campounds 3 and 4 gave characteristic pseudomolecular ions, [MH]', whichappearasthebasepeakfor4, and with a relative intensity of 89.5 % for 3.

Reaction nwdumim

?he formation of diethyl ( E)-l-( 3-fluompmpanoyl- q)-3-fluompmp-l-enylphosphonate (3) is most reason- ably explained ( Scheme 3) by assuming relatively fast electmphilic attack by a second molecule of acyl halide on the carbonyl oxygen atom of the fmt-formed acylphospho- nate 5 and the loss of a proton fmrn the a-methylene p u p of the latter. 'Ihe only previous reference to acyla- tions of this type' reported the formation of I-acyl- oxylvinylphosphonates fmm diakylacylphosphonate and acyl chlorides in the presence of triethylamine, the latter being assumed to generate the enolate anion of the acylphosphonate as a reactive intermediate. Depmtonation of the rnethylene p u p of 3-fluom derivative ( 5 ) clearly occm in the absence of added base and is likely to be favoured by the combined electron-attracting effects of the adjacent fluommethyl and carbonyl p u p .

scheme3

3

The formation of diethyl 1 - ( diethoxyphosphoryl ) -3- fluompmpyl phosphate ( 4 ) can be assumed to occur (Scheme 4) via nucleophilic attack of a second molecule of phosphite on the carbonyl group of the acylphosphonate 5 to give a carbanion 7, followed by protonation and

1600 Fluorinated organophosphonate WU&HarryR.

dedkylation. A source of acid is available from the elimi- nation reaction leading to the fomtion of the l-acyl- oxypropenylphosphonate (3) (Scheme 3 ) , and is a pre- requisite for the reaction shown in Scheme 4 to occur. "he presence of a trace of adventitious moisture cannot be totally excluded, but water alone does not appear to be s&cient to p m t e this type of reaction. Analogous products have, however, been obtained in the reaction of trialkyl phosphites with m y 1 chlorides in the presence of added proton donors, e. g . , alcohols or &xylic acids,g"o and in the reaction of trimethyl or triethyl phos-

lowed by quenching with methanol." In each case a car- banion intermediate was assumed to be formed and to be trapped by the protic reagent.

phite with perfluoroa~yl chlorides in THF at - 78 "c , fol-

"he fomtion of hydrogen chloride (Scheme 3 ) may also be expected to lead to deakylation of triethyl phos- ph~te to give diethyl phosphite , l2 which can itself undergo addition reaction with an acylphosphonate to give the cor- responding a-hydroxy-1,l-bis ( phosphonate)13 ( in this -, compound6).

In conclusion, the p m n t results exemplify a novel interdependence between two types of reaction that can

OCCUT between triakyl phosphites and acyl chlorides, one occuning in the molecular ratio of 1 :2 and n o d y re- quiring the presence of tertiary base, and the other occur- ring in the molecular ratio of 2: 1, and requiring the pres- ence of a proton donor. "he critical factor in the overall course of reaction in the present case appears to be the presence of fluorine in the 3-position of the pmpanoyl chain and the consequent ease with which the acylated

propenylphosphonate 3 is formed, making hydrogen chlo- ride available in the reaction system (Scheme 3) .

Insecticidal &y

Activity against M w a domestics L. (housefly) and Phaedon cochlednae ' Fab. (mustard beetle) was assessed by topical application of solutions of the compounds in acetone. The results showed that at 20 pg per insect, di- ethyl ( E ) - 1 - ( 3-fluoropropanoyloxy ) -3-fluoroprop 1 - enylphosphonate (3) gave 100% control of both species (LDS for mustard beetle=5.0 pg per insect). Diethyl 1- ( diethoxyphosphoryl -3-fluoropropyl phosphate ( 4 ) was less active, giving 8% and 25% control only of these two species, respectively, at the same rate of application (8% in h o d y is equivalent to control mortality). Whereas vinyl phosphates m known to be active insecti- cides,I4 it is surprising to observe activity in a vinylphos- phonate such as compound 3, which does not possess an obviously suitable leaving group for it to be an acetyl- cholinesterase inhibitor. The reason for activity in 3 is as yet uncertain but the possibility of molecular rearrange- ment in which €'-C is replaced by EL0 should be con- sidered.

Experimental

3-chloropropan-1-01 and triethyl phosphite were ob- tained fmm Aldrich. "he 3-chloropropan-1-01 was con- verted successively, by described procedures, into 3-fluo- ropropawl-01, 3-fluompmpanoic acidI3 and 3-fluoro- propanoyl chloride, b. p. 51-52 "r: at 8.93 x I d Pa (lit.15 b.p. 52 "r: at 9.33 x I d Pa).

Specfto~co~and-n

NMR spectra were recorded on a Bruker AM250 in- sh-ument for solutions in cDc13. Chemical s& am in ppm downfield from TMS ( 'H and l3 C spectra), &F6 ("F spectra), and 85% H3PO4( external reference, 31 P spectra). Mass spectra were obtained on a Kmtos Profile instrument, using a glycerol matrix and with a Cs' ion gun operating at 10 kV. Micloanalyses were carried out with a Carlo Erba 1106 elemental analyzer.

Vol. 20 No. 12 2002 Chinese Joumal of Chemistry 1601

Reaction of 3 - ~ u o r o p r o ~ ~ chloride with triethyl phos- Phk

3-Fluoropmpanoyl chloride ( 11.3 g, 0.10 mol) was added dmpwise, under nitmgen, to triethyl phosphite (17.0 g, 0.1 mol) at 0-5 "r: with vigorous stirring. Stirring was continued ovemight at room temperature and volatile products were then removed at 66.6 Pa. 'Ihe colourless liquid residue was subjected to column chro- matography on silica gel, with a mixture of ethyl acetate and light petroleum (1: 3, V : V ) as eluant, to give a main fraction which was concentrated and dried over an- hydrous magnesium sulphate to give diethyl ( E)-l-( 3- fluompropanoyloxy ) -3-fluo~prop- 1-enyl-phosphonate (3) (6.0 g, 59.2%); 'H NMR (CDCl,, 250 M H z ) 6: 1.34( t , J =7.06 Hz, 6H), 2.89 (dt, J =5.72, 25.43 Hz, 2H), 4.06-4.23 (m, 4H ), 4.76 (dt, J = 5.73, 46.35 Hz, 2H), 4.95 (ddd, J = 3.10, 5.40, 46.34 Hz, 2H), 6.61 (overlapping ddt, J = 5.4, 1 1 . 0 , 16.05 Hz, 1H); I3C NMR ( C D C l 3 , 63 MHz) 6: 16.10 ( d , J = 6.67 Hz), 35.18 ( d , J = 22.77 Hz), 63.15 (d, J=5.03 Hz), 77.39 (dd, J = 15.16, 165.01 Hz), 78.77 ( d , J = 168.62 Hz), 131.52 (dd, J=24 .84 , 22.08Hz), 139.89 (dd, J = 226.99, 10.00 Hz), 166.99 ( 9 ) ; 19F NMR (CDC13,

(d , 1=0.71 Hz ); 31P NMR (CDC13, 101 MHz) 6: 7.20 ( d , J = 1.16 Hz); Ms m / z (a): 287 ([MH]' , 89.5). Anal. calcd for CloH17F20aP: C 42.0, H5.9; foundC41.7, H5.8.

Further elution from the column with methanol gave a second (crude) product which was purified by chro- matography on alumina, using ethyl acetatdlight petroleum ( 2 : 1, V : V ) , to give diethyl 1-(di- ethoxyphosphinyloxy ) -3-fluoropropyl phosphonate ( 4 ) (3.89 g, 33.3%). 'H NMR (CDCl3 , w) M H z ) 6: l . P l . 4 0 (m, 12H), 2.04-2.48 (m, 2H), 4.08-4.30 (m, 8H), 4.65 (m, J=47.14Hz, 2H), overlapping with 4.71-4.86 (m, 1H); I3C NMR (CD- Cl,, 63 M H z ) 6: 16.08 (d, J=6.98 Hz), 16.05 (d , J = 7 . 0 9 Hz), 16.43 (d , J=5.75 Hz), 16.48 (d , J =5.64Hz), 32.09(dd, J=21.01, 2.53Hz), 63.15 (d , J=7 .14 Hz), 63.18 ( d , / = 6 . 2 9 Hz), 64.30 (d , J=5.92 Hz), 64.33 ( d , J=5 .91 Hz), 69.06 (ddd, J=172.79, 5 . 0 9 , 7.16Hz), 79.38 (dd, J = 166.57, 12.12 Hz); 19F NMR (CDC13, 235 MHz) 6:

235 MHz) 6: - 52.36 (d , = 0.59 Hz), -56.72

-54.93 ( d , J = 1.61 H z ) ; 31P NMR (CDCl,, 101

MHz) 6: 19.68 (d , J=20 .34 Hz), -0.60 (d , J = 21.29 Hz); MS m / z (%) : 351 ([MH]', 100). Anal. calcd for CIIH~IQP: C 37.72, H 7.19; found C 37.86, H 7.19.

Acknowledgements

We thank the Sino-British Friendship Scholarship Scheme for pmvidmg a schohhip (for Wu Jun) and the British Council for &uncial support. We are also grateful to British Technology Group for their interest and for pro- viding access to insecticidal screening facilities.

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