An answer to the spiro versus ansa dilemma in cyclophosphazenes

Journal of Molecular Structure, 96 (1982) 113-120 Elsevier Scientific Publishing Company, Amsterdam -Printed

AN ANSWER TO THE SPIRO VERSUS CYCLOPHOSPHAZENES

in The Netherlands

ANSA DILEMMA

IN

Part II. * N3P,Cl, [ HN-(CH&-NH]

GUY GUERCH**, JEAN-FRANCOIS FRANCOIS SOURNIES

LABARRE,

RAYMOND ROQUES and

Laboratoire StmAw-e et Vie, Universitt! Paul Sabatier, * Toulouse Cedex (France)

118 Route de Narbonne,

31062

(Received 19 March 1982)

ABSTRACT A structural investigation, mainly by mass spectrometry and X-ray crystallography, of the products obtained from reaction of butylenediamine and N,P,Cl, shows that the major product is unambiguously the Spiro derivative N,P,Cl,[HN-(CH,),-NH] , the dispiro compound N,P,Cl,[HN-(CH,),-NH] z being observed as a side-product. Thus, butylenediamine behaves like propylenediamine and ethylenediamine although the yield of the main monospiro product decreases significantly as the length of the methylenic chain of the diamine increases. INTRODUCTION

The reactions of N3P,C!1,with difunctional reagents lead to products of which the structures have been disputed. Becke-Goehring and Boppel maintain that an ansa structure [l] is obtained whereas Shaw and co-workers opt for the Spiro configuration [ 21. Thus, it was deemed necessary to carry out a systematic structural investigation of the products of the reaction of N3P3C16 with large difunctional reagents. Conclusive evidence for a Spiro structure for N3P3C14[HN-(CH2)3-NH] [3] was recently obtained and it was shown that in this case neither any ansa form nor dispiro side-product resulted from the reaction of hexacyclotriphosphazene with propylenediamine. The present paper reports the structures of the products of the reaction of N3P3C16with butylenediamine. EXPERIMENTAL

The synthesis was done following standard methods [2,3] in the presence of NE&. A non-polar solvent (70% petroleum ether 60-80” C, 30% CH:C&) was used in order to minimize the formation of non-crystalline resins (cyclo*For Part I see ref. 3. **Author for correspondence. 0022-2860/82/0000-0000/$02.75

0 1982 Elsevier Scientific PunIishing Company

114

linear and/or cycle-matrix polymers). It is well known that polar solvents (e.g. diethyl ether, DMSO) lead to a proton-abstraction process from the PNHR groups thus promoting polymerization [4, 51. The yield of the reaction was 65%. Thin-layer chromatography (t.1.c.) gave two spots: a large one (A) at R, = 0.51 and a smaller one (B) at R, = 0.65 with CC14-CH2C12 (3:7) as eluant. It is noteworthy that the resins are initially soluble in organic solvents but harden and become insoluble on storing for 2-3 days, except in acetone. The IR spectrum of such a resin shows a strong broad absorption band at ca. 1200 cm-l suggesting that the six-membered N3P3ring is retained. Separation

of A and B by SiO, column

chromatography

A crude mixture (85% A + 15% B) was submitted to SiOZ column chromatography using CC14-CH2Clz (3 :7) as eluant. A and B were then readily separable in high yield. Their melting points were 179 and 148.5” C respectively. Mass spectrometry

Spectra were recorded on a RlOlO Ribermag quadrupole mass spectrometer using a direct inlet system. The source temperature was 150°C and electron energy 70 eV. Spectra were analyzed by means of a DEC PDP 8/M computer and stored on a disk. A small sample (“1 pg) was introduced onto the probe, the ternperature of which was then gradually increased from ambient to 100” C taking care that neither the electron multiplier nor the amplifier were in a saturated condition at any time. The areas under the curves corresponding to the current carried by the selected ions were calculated by the computer. The 70-eV electron impact mass spectrum of A is shown in Fig. 1. The molecular ion was observed at m/z 363 (100%) with a set of satellites at m/z 364 (14.6%), 365 (55.0%), 366 (6.7%) and 367 (11.2%). The intensity ratio of these five peaks indicates the presence of four chlorine atoms in the molecule. Two other satellites of the molecular ion were observed at m/z 362 (15.7%) and 361 (87.6%), corresponding to the loss of 1 and 2 H atoms respectively. One main fragmentation route involves successive loss of 1 CH2, 2 CH2, 3 CH,, 4 CH?, 4 CH2 + 1 NH and 4 CH, + 2 NH (associated with H-transfers) to give maximal peaks at m/z 348 (19.1%), 335 (12.3%), 320 (16.8%) 307 (40.4%)) 292 (15.7%), 277 (21.3%). Further consecutive loss of Cl atoms gives peaks at m/z 242 (41.5%), 206 (8.9%) and 170 (7.8%). A second fragmentation route is observed: starting from the molecular ion, peaks are observed at m/z 328 (15.7%), 292 (15.7%), 257 (19.1%) and 221 (10.1%) which correspond to the successive loss of one to four chlorine atoms (again associated with H-transfers) from the molecular ion. Each of these four fragments gives a related peak corresponding to the loss of one CH2 group from the Spiro loop at m/z 311 (23.5%), 278 (66.2%), 243 (17.9%) and 207 (8.9%) respectively.

115

I

1

I

1

90

I

130

I

170

I

210

250

290

330

370

410

L 0

m/r

Fig. 1. 70eV electron impact mass spectrum of N,P,Cl,[HN--(CH,),-NH].

In the low mass range, several peaks can be attributed to certain fragments: [HN-(CH,),-NH], m/z 86 (7.8%); [N-(CH,),], 70 (85.3%); [N-(CH,),CH], 69 (32.5%); [N-(CH,),-C] ,68 (16.8%); [N-(CH,),-C-C] ,66 (21.3%); [N-(CH,),], 56 (71.9%); [N-(CH,),-CH], 55 (16.8%) and [N(CH,),-C], 54 (30.3%). The intensity of all other peaks is less than 2%. Thus, it is a relatively simple matter to check for the presence of any possible contaminant. Mass spectrometry again appears to be an adequate tool for monitoring the purity of a cyclophosphazene [6] . Furthermore, since the fragmentation pathways of product A are identical to those previously observed [3] for the spiroN3P3C14[HN-(CH2),-NH] derivative, it seemed reasonable to assign a spiro structure to A. X-ray crystallography (see below) unambiguously supports this conclusion. In the same way, a dispiro structure, i.e. N3P3Cl, [HN-(CH,),--NH] 2, could be assigned to B, the fragmentation routes in this case being quite similar to those of A. NMR spectroscopy

The 31PNMR spectrum of A was recorded on a Brucker WH 90 instrument. The doublet at 21.41 and 20.18 ppm undoubtedly corresponds to PC&entities and the triplet around 13.07 ppm (14.36,13.07 and 11.78 ppm) to the P (spiro) moiety (intensity ratio 2: 1). These chemical shifts are compared with those previously reported for other N3P3C14[HN-(CH,),-NH] homologues (Table 1). It can be seen that the gap, A, between the doublet and the triplet does not parallel the variation in 12:A is ca. 0 for IZ= 2, reaches its maximum (about lg.2 ppm) for 12= 3 and then decreases again to .

116

7.7 ppm for n = 4. Moreover, some preliminary investigations of higher homologues (n = 5 and 6) [7] indicate that A falls to zero for such values of n. No reasonable explanation for such a variation in A can be proposed until X-ray structures for the whole series have been performed: crystallography is the only technique which may both support the Spiro assumption and provide the reasons (geometrical and electronic) for the changes in the 3 ‘P chemical shifts. When the NMR spectrum of A is recorded in a non-polar solvent (CC& or n-hexane), a triplet--quadruplet substructure superimposed in a “comb-like” pattern on the primary doublet-triplet main structure (Fig. 2) appears. Such a triplet-quadruplet secondary pattern implies the existence in solution of an intermolecular (P**P) coupling, probably through hydrogen bonds as is the case for N3P3C1, [HN-(CH,),-NH] [S] . This assumption is supported by the fact that the secondary structure disappears in highly polar solvents. Infrared spectroscopy The IR spectrum (KBr disk) was recorded on a Perkin-Elmer 683 spectrometer (range 4000-200 cm-‘, calibrated with polystyrene). This spectrum was found to be very similar to that of N3P3C14[HN-(CHZ ),-NH] [ 31, except in the 3200-3450 cm-’ region where A exhibits three (N-H) bands at 3240,333O and 3430 cm-’ whereas N3P3C14[HN-(CH,)3-NH] is character, ized by a unique band at 3270 cm-‘. A thorough investigation of the way in which the intensities and wavelengths of these stretching modes vary with the solvent is now in progress in order (i) to assign the precise nature of the various (N-H) bands and (ii) to measure the acidity (in the Lewis sense) of the corresponding protons. The latter factor is of real importance in the design of anticancer drugs having a strong affinity for DNA [9] : the higher the acidity, the stronger the affinity of the chemical for DNA and, presumably, the greater its anticancer activity. X-RAY CRYSTAL AND MOLECULAR

STRUCTURE

Compound A spontaneously provides suitable single crystals as a result of its synthesis, contrary to B, single crystals of which large enough for X-ray TABLE 1 31P NMR data (ppm) for some N,P,CI, [HN-( CH,),-NH]

derivatives

N,P,Cl, [HN-( CH,),-NH]

Center of doublet

Center of triplet

A

Ref.

n=2 n=3 n=4

23.5 20.74 20.82

22.8 7.58 13.07

0.7 13.16 7.75

a 3 This work

aH. G. Parkes and R. A. Shaw, Proceedings of the 3rd Inorganic Rings International Symposium (IRIS Meeting), Graz, Austria, August 1981, p. 40.

117

H,PO. 20.18 +

21.47

+ 14.36 13.07 20.82

II.78

++

++

ZZ.ll

i

I I -x-73->‘-

Y

+ 13.72

19.53 +

u 15.01

I

12.43 =?

I I u = --czgypp=-

II.13

ii

0.65

Fig. 2.“Comb-1ike”triplet-quadruplet

substructure

of the primary

doublet-triplet

pattern.

study could not be obtained. Thus, only the preliminary results r’or A are reported here. The crystal structure of A was determined on an automatic Syntex P21 diffractometer. Data collection required three successive crystals due to the slow decomposition of A on exposure to X-rays. Thus, the R factor was never greater than 0.10. Only approximate bond lengths and bond angles are therefore reported in Tables 2 and 3. A crystallizes in the monoclinic system, space group P2,/c, with cell parameters a = 10.463(3), b = 17.174(5), c = 16.239(5) A, P = 102.53(3)“, V= 2849(2) A3, d, = 1.69 Mg rne3, z = 8. Two crystallographically independent molecules, A(1) and A(II), coexist in the asymmetric unit. A perspective view of the A(1) molecule is shown in Fig. 3 in which the numbering of the atoms is indicated. This view emphasizes the spiro structure with the sixmembered phosphazene ring strictly non-planar. A second view (with the N3P3 ring in the plane) shows significant puckering of the spiro loop (Fig. 4) both in A(1) and A(I1). The N3P,N,i plane is not strictly perpendicular to the TABLE Tentative

2 bond lengths

(A) in the A(I)

and A(I1) forms

of N,P,Ci,[HN-(CH,),-NH]

Bond

A(I)

AUI)

Bond

A(I)

A(II)

PI--N, PI-N, i PI--N, P,-N,i P,-N, Pzi-N,i P,--N, Pzi-Nz

1.61 1.58 1.61 1.62 1.58 1.59 1.55 1.58

1.58 1:61 1.62 1.61 1.55 1.57 1.55 1.58

PSI,

2.02 1.98 1.98 2.00 1.47 1.48 1.54 1.51 1.52

1.99 2.00 2.01 2.00 1.47 1.46 1.51 1.54 1.50

P,--Ci: P*t-Cl,i p2i+1*i

Cl-N, Cxi-N,i C,--C, .

czi-c*i G--C2i

.

118 TABLE 3 Tentative bond angles (“) in the A(1) and A(I1) forms of N,P,Cl,[HN-(CH,),-NH] Bond angle

AU)

AW)

N,-P,--N,i N,-P,--N,i PI--N,--C P,--N,i-Cli P,-N,-P, P,-N,-P,i N,-P,i-N,i P,--N,i-Pzi Cl,--P,-Cl, Cl,i-P*i-Cl*i N,-C--C, C*-cz--czi C,i-C,i-C* C,i-N,i-P,

113.5 105.2 120.8 123.7 120.8 118.5 118.0 125.3 99.2 99.8 112.7 113.8 116.1 123.7

113.6 104.9 121.9 122.4 121.1 119.4 118.4 123.8 100.4 99.1 117.4 117.2 115.5 122.4

phosphazenic ring, the angles between these two planes being equal to 98.0 and 99.2” respectively. In other words, the two exocyclic phosphorusilitrogen bonds deviate by 8.0 and 9.2” from the expected uVforward planes containing the P, and N2 atoms. It is noteworthy, however, that this N,P,N,i plane contains atoms Cz and CZi,carbon atoms C1 and Cli deviating by ca. 0.70.4 above and below this plane. The main feature of the structure is observed around P,: the presence of the loop pulls P1 away from Nz, endocyclic PI-N1 and PI-NIi bonds being larger (1.595 a) than the average value (ca. 1.58 a) of the other phosphorusnitrogen bonds of the ring. Consequently, the N, P, Nli angle is smaller (113.5”) than the values (ca. 119”) observed around P, and P,i. In other words, both the NIPIN1i and N3P1N3iangles are squashed. As the result of such a molecular internal stretch along the PI---N2 direction, the P1 atom appears to be in a pseudo-tetrahedral environmental: (P,-N,,,) = 1.62(5) 8; (PI-Nendo) = 1.59(5) 8; (N,,,-P,-N,,,) = 105.0”; (N endo-P I-Nendo ) = 113.5”. Such a Td-like environment for a P atom

Fig. 3. A perspective view oFN,P,Cl,[HN-(CH,),-NH]

showing the Spiro structure.

119

Fig. 4. Perspective views of the-A(I) and A(I1) ing the puckering of the spiro loops.

forms

of N,P,Cl,[HN-(CH,),-NH]

show-

belonging to a trimeric ring is extremely unusual in cyclophosphazenes and may explain [ 31 the peculiar NMR behaviour manifested by P,. However, a complete refinement of the X-ray structure of A is necessary to quantify the variations in A as a function of n (see above). The packing of eight molecules of A in the monoclinic unit cell suggests intermolecular hydrogen bonds (as demonstrated by the short distances between some of the heavy atoms of different molecules). A precise description of these hydrogen bonds awaits a fulI refinement of the structure, including the location of the hydrogen atoms. CONCLUSIONS

X-ray crystallography and mass spectrometry have been used to prove that the main product obtained from the reaction of N3P,C16 and butylenediamine has a Spiro structure and not an ansa one. A side-product is also observed, the structure of which seems to be of the dispiro type. Thus, butylenediamine behaves like propylenediamine [ 3,8] and ethylenediamine [ 10,111 although the yield of the side-product with a dispiro structure is expected to increase markedly with the size of the difunctional reagent. ACKNOWLEDGEMENTS

We are indebted to Dr. R. Lahana for computational support and skilful visualization of molecular conformations by means of an APPLE II computer. REFERENCES 1 M. Becke-Goehring and B. Boppel, Z. Anorg. Allg. Chem., 322 (1963) 239. 2 S. S. Krishnamurthy, K. Ramachandran, A. R. Vasudeva Murthy, R. A. Shaw and M. Woods, Inorg. Nucl. Chem. LetC, 13 (1977) 407.

120 3 G. Guerch, M. Graffeuil, J.-F. Labarre, R. Enjalbert, R. Lahana and F. Sournies, J. Mol. Struct., 95 (1982) 237. 4 S. K. Das, R. Keat, R. A. Shaw and B. C. Smith, J. Chem. Sot., (1965) 5032. 5 S. S. Krishnamurthy, A. C. Sau, A. R. Vasudeva Murthy, R. Keat, R. A. Shaw and M. Woods, J. Chem. Sot., Dalton Trans., (1976) 1405; (1977) 1980. 6 B. Monsarrat, J.-C. Prome, J.-F. Labarre, F. Sournies and J. C. Van de Grampel, Biomed. Mass Spectrom, 7 (1980) 405. 7 G. Guerch and F. Sournies, unpublished results. 8 R. Enjalbert, G. Guerch, J.-F. Labarre and J. Galy, Z. Kristallogr., Kristallgeom., Kristallphys., Kristallchem., (1982) in press. 9 J.-F. Labarre, Top. Curr. Chem., 102 (1982) 1. 10 Y. S. Babu, H. Manohar, K. Ramachandran and S. S. Krishnamurthy, Z. Naturforsch., Teil B, 33 (1978) 588. 11 S. S. Krishnamurthy, K. Ramachandran, A. R. Vasudeva Murthy, R. A. Shaw and M. Woods, J. Chem. Sot., Dalton Trans., (1980) 840.