THE STEREOCHEMISTRY OF ORGANOPHOSPHORUS COMPOUNDS

COMMUNICATION i. CONFIGURATION AND CONFORMATIONS OF 2-SUBSTITUTED

OXA PHOSPHOLA N-3-OLS

R. R. Shagidullin, Yu. Yu. Samitov, UDC 541.63:547.1'118 F. S. Mukhametov, and N. I. Rizpolozhenskii

It has been shown previously that the react ion of fi-keto alcohols with dichlorides of acids of t e r - valent phosphorus in the presence of organic bases fo rms derivat ives of oxaphospholan-3-ols [1, 2]. Con- tinning an investigation of this p rocess , we have studied the react ion of phosphorous, phosphoramidous, and a lkyl- and arylphosphonous dichlorides with diacetone alcohol in the presence of t r ie thylamine and have obtained a se r ies of new oxaphospholanol derivat ives (Table 1). In two cases , f rom the react ions of N,N- diethylphosphoramidous and phenylphosphonous dichlorides with diacetone alcohol it was possible to isolate two producLr with sharp melting points in each case: 125-126 ~ (I) and 118-119 ~ (V), and 135-136 ~ (II) and 164-165 ~ (VI). According to e lementary analysis , the members of each of these pairs of products bad the same composition. The IR and PMR spect ra of these pairs of substances showed the same functional group- ings and s t ruc tura l f ragments agreeing with the formulas of the corresponding oxaphospholanols. An an example, Figs. 1 and 2 give the spec t ra of (I) and (V).

The II~ spect ra of (I) and (V) show the charac te r i s t i c hydroxyl adsorption in the 3200 cm -1 region. At 1220 cm -1 there is s t rong vp =O absorpt ion and at 1170 cm -1 an intense v C_OH multiplet [3]. The single high peak at 1020 cm -1 present in both spect ra can be ascr ibed to VC_NP [4], and a group of strong absorpt ion bands at 900-970 cm -1 to the s t re tching vibrations of the cyclic skeleton and of the P N R 2 group [4]. A se r ies of bands in the 700-900 cm -1 region may also be due to the vibrations of the substituted ring, VP_NR2, and also to PCH2 [3, 4]. The spec t rum of (I) differs f rom that of (V) by a band at 670 cm -I, which

must be asc:.~ibed to 7OH nonplanar deformation vibrations [3]. In view of the different s trengths of the hy- drogen bond~, the corresponding frequency in (V) is shifted to ~715 cm -~. In the 500 cm -~ region, the spec t ra sho~v a group of bands which can be ascr ibed to the deformation vibrations of the skeleton, in par - t icular to 5p =O.

It follows f rom the PMR spect ra (see Fig. 2) that the proton of the hydroxy group appears in the form of a singlet iiine with 5 5.17 ppm in (I) and 5 3.90 ppm in (V). Because of the a s y m m e t r y of the phosphorus atom the methylene groups of the X-N(C2Hs) substituent are diastereotopic, and consequently they a re magnet ical ly nonequivalent and appear in the fo rm of a complex multiplet of bands with 5 3 ppm, and the methyl grou~s show a tr iplet with 5 1.10 ppm. The methyl group at C 3 gives a doublet (6 1.38 ppm, JPCCH 3 15 Hz). A gem-dimethyl grouping at C~ in both i somers leads to two singlets with 5 1.35 and 1.55 ppm in (I) and 5 1.33 and 1.53 ppm in (V). The methylene protons of the ring resonate in both compounds in the form of a complex multiplet (octet) band with 6 2 ppm.

Thus, it may be assumed that during the react ion different i somers were obtained. The s t ruc tura l formula of the expected oxaphospholanols show the possibili ty both of configurational and conformational i somers . The f o r m e r are due to the presence of four nonequivalent substituents at the P - C bond of the r ing and the la t ter to the mobili ty of the f ragments of the ring. The i somers corresponding to the different configuratio:as may be provisionally called " t rans" (A) and "cis" (B) in relat ion to the mutual a r rangement of the projections of the P =O and C - O H bonds on the plane perpendicular to the plane of the OPC angle of the ring:

A. E. Arbuzov Institute of Organic and Physical Chemistry of the Academy of Sciences of the USSR. Trans- lated from I~vestiyaAkademiiNaukSSSR, Seriya Khimicheskaya, No. 7, pp. 1604-1612, July, 1972. Original article submitted December 25, 1970.

�9 1!~7J Consultants Bureau, a division of Plenum Publishing Corporation, 227 West 17th Street, New York, N. '/. 10011. All rights reserved. This article cannot be reproduced for any purpose whatsoever without pertaission of the publisher. A copy of this article is available from the publisher for $15.00.

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TABLE 1.

0 O--C(CHs)~

• \ I C--CH2

/ \ CHa OH

C o r n =

pound

I

[I

III

IV

V

vI

VII

VIII [2]

(C~Hs)2N

C~H5

CzH5

(CH3hN

[C~Hs)2N

C~H5

S6H 50

~2H 50

rap," C

t25--126

135--i36

82--83

t40--t4t

tt8--1t9

t64--165

126--i27

100--t0t

Found % calculated!'

C H

50,83 9,42 9E~

60,30 7,29

50,34 9,14

46,12 8,59

5t ,02 9,40

60,20 7 ,t2

56,49 6,80

i3,23 t3,t6 12,94 12,89 i6,07 t6,t2 t4,84 14,95 12,78 t3,16 t2,60 I2,89 tt ,90 t2,t8

35gg 360g

0 CH8 0 OH \ / \ / P--C P--C

S \0H S \CH3 (A) (B)

In the i s o m e r (A), an i n t r a m o l e c u l a r H bond m a y be p e r m i t t e d be tween the hydroxy group and the s u b - s t i tuen t X, and in the i s o m e r (B) one with the P =O group. In each of the i s o m e r s , i n i t s tu rn , the pos - s i b i l i t y m u s t be a s s u m e d of the a p p e a r a n c e of one ec l ipsed (C) and two gauche (G) con fo rma t ions :

Me 0 0 0

OH (c) (0) (o)

H H

X Me ble

(c) (o) (0')

(B)

As men t ioned above, in the IR s p e c t r a of the oxaphospholanols unde r c o n s i d e r a t i o n in the sol id phase b road s t rong bands a t ~3200 cm -1 a r e obse rved (see Fig. 1). In so lu t ions of the s u b s t a n c e s in CC14, the i n t e n s i t i e s of t hese bands d e c r e a s e with i n c r e a s i n g d i lu t ion and they d i s appea r at c o n c e n t r a t i o n s of ~10 -4 M. Thus , this a b s o r p t i o n (VOHassoc.) m u s t be a s c r i b e d to e x t r e m e l y s tab le i n t e r m o l e c u l a r a s s o c i a t i o n s f o r m e d by m e a n s of H bonds.

As VOHassoc. d i s a p p e a r s f r o m the spec t r a , new bands appea r on the h i g h - f r e q u e n c y side. Ne i the r the pos i t ion nor the f o r m of the l a t t e r depends on f u r t he r changes in the c o n c e n t r a t i o n of the so lu t ions , which i nd i ca t e s that they be long to nonbound m o l e c u l e s . It can be s e e n f r o m the f i gu re s of Tab le 1 that each of ' the i s o m e r s (I) and (V) has one VOH band of unbound m o l e c u l e s - VOHnonassoc" However , the f r e q u e n c i e s , i n t e n s i t i e s , and widths of these bands a r e d i f ferent . The se d i f f e rences show that in (I) t he re is a s t rong i n t r a m o l e c u l a r hydrogen bond. IN (V), however , vOHnonassoc" m u s t be a s c r i b e d e i the r to a weaker i n t r a m o l e c u l a r H bond or to the v i b r a t i o n s of a f r ee OH group. On the b a s i s of ideas on the g r e a t e r

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~0

b

I ~ I I I I -, ~?~/gO 3#0# 25#/7 Z2OB l#O# " HIO# IOOO #O# 700 600 JO#- crn -~

Fig. 1. IR spectra of: a) 2 -d ie thy lamino-2-hydroxy-3 ,5 ,5 - t r imethy l - 1 ,2-oxaphospholan-3-one (V) (mull ir~ paraffin oil); b) 2-diethyl- amino-2 -hydroxy-3 ,5 ,5 - t r ime thy l - l , 2 -oxaphospho lan-3 -one (I) (mull in paraffin oil).

d IIIII -OH

= , =

r,~, $

\ \ \ 5 e e3-CM3

z,/z x~-/J2

__j~ , ;:2# uppm

Fig. 2. PMH spectra at v 0 = i00 MHz; a) 2-diethylamino-2- hydroxy-3,5, 5-trimethyl-l, 2-oxaphospholan-3-one (V), 15% solution in CHCI 3 at 19 ~ b) 2-diethylamino-2-hydroxy-3,5,5- trimethyl-l,2-oxaphospholan-3-one (I), 15% solution in CHCI 3 at 23 ~ .

e lect ron density of the cloud on the phosphoryl oxygen due to the polarization of a ~-bond, the i somer with the more prono~mced in t ramolecular H bond can be immedia te ly ascr ibed to (B) and the other to (A). How- ever, a considerat ion of the geomet ry of the molecules and the use of the usual values of the interatomic distances and angles between the bonds for a te t racoordinated phosphorus atom [5] shows that in (A) the OH group must approach the substituent X more c losely than the 0 atom of the phosphoryl bond.

For cyclic eompounds this difference must increase . Thus, it is not excIuded that in (A) there could be more favorable conditions for the formation of in t ramolecular hydrogen bonds.

H H

~.o 1,87 ~" ~ 116 ~ ~ 109 ~ , 102o o 1099 1,87

A 13

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R 0 OH Ix II I

TABLE 2. ~P--C--Ra R~, RT4

00111- pound R~ I~,

IX

X

XI

XII

XIII

02H5

CHs0

CHaO

CHsO

CHaO

C~H5

CH~0

CHaO

CHa0

CHaO

R, R,

CH~ CH2C~H 5

CH3 C8H5

CH~ CH 8 CHe--CH2

--C( I CH~--CH~

CC13 ]H

B OH-absorption A

36/O

X ,Y567 ,YFOI

X" 3576 ~ 3598

3577 ! 3597

( I ' , 3500 3500

o

The IR spect ra of the other oxaphospholanols obtained have been studied (see Table 1). The two i somers (IT) and (VI) also proved to be i somers with a "low-frequency" and a "high-frequency" VOH nonassoc. The spectra of all the other phospholanols showed only the "high-frequency" band. Consequently, com- pounds (I) and (II) belong to one type of i somers and (IIT) and (VIII) to the other. The i somer (II) can ap- parently be ascr ibed to (B), since the shift AvOH in its spect rum is unusual for H bonds with the par t ic ipa- tion of ~-elect rons [6].

Fur the rmore , a completely regular change is found in the position of the "high-frequency" band on passing f rom compound to compound. With an increase in the e lec t ron-accept ing prop6rt ies and, conse- quently, in the e lect ron-densi ty of X, VOH shifts to longer wavelengths and broadens. This can be con- s idered as proof of the fact that the "high-frequency" peak corresponds to an in t ramolecular H bond with X. It is true that if it is assumed that in the i somer (B) the in t ramolecular H bond is formed not with oxygen but with the ~-elect rons of the phosphoryl bond, in this case VOH must aiso fall with an increase in the e lectron-accept ing propert ies of X. In actual fact, in these c i rcumstances the ~-e lec t ron density of the

phosphoryl bond should r i se (O ~= P ~ X) and, consequently, the H bond should become stronger .

For fur ther study, we took the IR spectra of a ser ies of derivatives of ~-hydroxyalloylphosphonic acids (Table 2). In all these compounds, rotational i somer i sm relat ive to the P-C(OH) bond is possible and, in accordance with this, the IR spect ra of dilute solutions of each of them (see [7, 8]) show two vOH bands of undissociated molecules (see Table 2).

It can be seen f rom the figures of Table 2 that for compound (IX) with the least electronegative sub- stituents attached to P (two ethyl radicals) and, consequently, the maximum polarization of the P =O bond, the maximum shift of the "low-frequency" bands in the long-wavelength direction, under otherwise iden- t ical conditions, is observed. At the same time, when X is C2H 5 it is incapable of forming H bonds. Conse- quently, the ' low-f requency" band is due to an in t ramolecular H bond with the participation of the phosphoryl oxygen and the "high-frequency" band is apparently due to the substituent X on the P atom. For (III) where X does not possess the capacity for forming a H bond, the value of VOH of 3608 cm -1 must be taken as the value of the frequency of the vibrations of a f ree hydroxyl bond - vOHfree in compounds of this type. The shift by ~10 cm -1 in the longwave direct ion as compared with voHf ree of te r t ia ry alcohols [3] may be caused by the inductive effect of the phosphoryl grouping. For (IX), the "high-frequency" band should be, as it were, also the band of voHfree . However, its frequency of 3597 cm -i is no higher than in the other compounds. This situation must be caused by the fact that the frequency of 3597 cm -1 re la tes to an OH group bound by an in t ramolecular bond with the benzene r ing present in this molecule. In this case, a shoulder at ~3610 cm -1 must be assigned to the voHf ree band. It is impossible not to direct attention to the fact that for (III) both the bands considered a re shifted considerably in the longwave direction. The shift Av with respec t to (X), (XI), and (XII) for the low-frequency band amounts to ~70 cm -i. This shift cannot be caused by the influence of the CC13 group, since according to information for alcohols [9] one such group causes a shift of not more than 35 cm -i. A considerat ion of S tua r t -Br i eg l eb models shows that s te r ic factors in the molecule of (XIII) make it necessa ry for the hydroxy group to take up the eclipsed position with respec t to the P =O (P -X) bond (conformation C). Evidently, the strengthening of hydrogen bonds taking place as a consequence of the mutual approach of the groupings also leads to the shift in the

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OH CH 3

H 3 ~ C H 3 ~ /~CH 3 HA CH30

u c 2 " - - - ' - / ~ - 1 ~ x x I ~ ~A "3c'

(II) ( IH ) (VI)

(D ( P - - C - - C - - H A ) = 85 ~ ~) ( p - - c - - C - - H B ) = 9 3 ~ r ( P - - C - - C - - H A ) = cD (p--c--C--HB)= 120 c'

J p H A = 3,9Hz ]pH A = 3,9 Hz

(D (P--C--C--H) = t 6 0 ~ op(P--C--C--H) = 140 ~

dpH B = 20,0 Hz Jpt_IB ~ 20,0 Hz

Fig. 3. Possible conformations of the 2-substituted oxaphos- pholan-3-ols.

bands that has been observed. But it follows from this, and also from a comparison of the spectra (see the figures of Tables i and 2) that in dilute solutions in CCI 4 the oxaphospholanols (D-(VIII) also exist in the eclipsed conformation (C) or one close to it. At the same time, the higher values of the frequencies of the bands considered in the rotational isomers of the ~-hydroxyalkylphosphonio compounds (IX)-(XII) point to the realization, in view of the absence of any special steric factors, of the gauche conformations (G)

or conformations close to them.

Thus, the considerations that have been expressed enable the oxaphospholanols obtained to be re-

liably identified. Compounds (I) and (If) are the "cis" isomers (B) and the other compounds (III-VIII) are the "trans" isomers (A). While the IR spectra permit an answer to the question of the nature of the oxa- phospholanoi( isomers and show that they are configurational isomers, the NMR spectra permit an analysis of the conformations of the rings. As test characteristics of the conformations of the five-member ring, we used the spin-spin coupling constants (SSCC), solvent effects, and also the relative chemical shifts of the

methylene p:.~otons ~CHAHB and of the gem-dimethyl grouping at C 5.

The PI.V[R spectrum of the methylene protons H A and H B of the oxaphospholane ring appear as a com- plex multipl3t with chemical shifts of 5 1.95 ppm (1) and 2.13 ppm (V), each consisting of eight lines. An analysis of the PMIR spectrum of the isomer (V) with mp 118-119 ~ shows that the vicinal spin-spin coupling of the phospaorus nucleus with the methylene protons of the ring takes place with different, but not very different, constants of JPH = 11.0 and JPH = 15.2 Hz, which is possible if the C-P bond in the ring almost eclipses the C4-C 5 bond. Such a conclusion has been drawn in [I0], where the spectrum of 2-phenyl-2- hydroxy-3,5,5-trimethyl-l,2-oxaphospholan-3-one has been described; JPH' and JPH" differ to a smaller ex- tent (II. 0 am] 11.7 Hz). These facts permit the statement that the molecules of (V) (in CHCI 3 solution) have predominantly the envelope conformation (Vl) (Fig. 3), inwhichthe P, C3, C4, and C 5 atoms are present in one plane, and the O atom departs from the plane in the direction opposite to that of the P=O bond. It must be obs,grved that this conformation is not the most favorable for intramolecular H bonds and requires further refinement. The predominant envelope conformation (Vl) is also confirmed by the influence of an aromatic solvent on the chemical shifts. When (V) is dissolved in benzene, one of the lines of the gem- dimethyl grouping is strongly shifted in the upfield direction. This is possible if the axial and equatorial positions of the methyl groups are realized in the conformation (VI). In agreement with the results of IR spectroscopy, the PMR spectra of (III)-(VIII) and (1) and (V) are similar to one another.

An analysis of the octet (two AB quadruplets) of the PMR spectrum of (I) (see Fig. 2) leads to the constants 3JpH A (~ ~ 90 ~ = 3.9 Hz and 3JpH B (~ ~ 140 ~ = 20 Hz. Such values of the constants are possible

only if the dissolved molecules of (1) have either predominantly the conformation (I') (see Fig. 3), in which the ring atoms O, P, C4, and C 5 are in one plane and the C 3 atom departs from the plane in the direction of the P =O bond, or predominantly the conformation (I"), in which the ring atoms O, P, C3, and C 4 are in one plane and the C 5 atom departs from the plane in the direction of the P =O bond.

A choice of the two conformations mentioned can be made by considering the solvent effect. We have performed a study for five solvents (CC14, C6H6, CH2CI2, (CD3)2CO , and CH3NO2). Figure 4 shows the posi- tions of the lines of the chemical shifts of the protons in the corresponding groups of atoms referred to infinite dilulion. The strongest influence on the position of the lines of the spectrum is shown by benzene. A characteristic feature is that the line of the CH 3 group attached to the C 3 atom is least subject to the in- fluence of the nature of the solvent. It is also fundamental that in benzene its line is shifted in the downfield

1 5 4 9

OH CH;

SOLVENT EFFECTS CH31C-3)

JAB =/q I p~ e o =Z, ZO0

I ' \ I %.~

\\% i I %,,.

Jp~=zo I - i i , . i elo :Z,303 I [ / I

/ /'J \ ,7" I " /

~'25 = 8, gJ , ,, ]

J p b = z # , q ~ , T p A = 3 , 0 {{;]}3'zCO / ~ - I / ~25-- 20, 7q I / ~ I I I I I ! I

Jps=ZO,3 ~ ,]-pA =',8 C H 3 N g 2 ~ i ,]'p;ff? lS, Z " E20 = 38, 57

I I I I I I t I ~ I - - I I ] I I L . . . . I Z,l /,b" pprn 55 l,O

Fig. 4. Influence of solvents on the positions of the chemical shifts and the values of the s p i n - s p i n coupling constants.

direction, while the lines of one of the methyls of the gem-dimethyl grouping and of one of the protons of the methylene grouping of the oxaphospholane ring a re shifted upfield. These features can be understood if it is assumed that the molecules of (I) remain in conformation (I") (see Figs. 3 and 4). With such a s t ruc ture of the molecule, the methyl group on the C 3 atom is less access ib le for interact ion with the molecules of the solvent because of the s te r ic hindrance created by the substituent X=N(C2Hs) 2. In the case of the predominant conformation{I'), onthe other hand, the methyl group would be subject to the dia- magnetic influence of the ~-elect rons of the a romat ic nucleus, i.e., its line should be shifted upfield, and not downfield as is observed experimentally.

The choice made is in agreement with the resul ts of the IR spectra, since it is just in conformation {I") that it is easiest to real ize an in t ramolecular hydrogen bond with the phosphoryl group.

The chemical shifts of the phosphorus nucleus - 531p = -41 .2 ppm for (V) and 53tp = -45 .6 ppm for (I) - confirm the conclusions drawn above on configurations and conformations. In the configuration and conformation (V) (see Fig. 2), the phosphorus atom must have a more symmetr ica l environment than in (I), and consequently in the la t ter case the chemical shift should be more negative [11].

E X P E R I M E N T A L M E T H O D

Compounds (I)-(VII) and (VIII) were obtained as described previously [2].

Separation of the I somers (I) and (V). The crude product of the react ion between diacetone alcohol and N,N-diethylphosphoramidous dichloride was recrys ta l l i zed f rom benzene giving a substance with mp 102-118 ~ This compound was subjected to fractional recrys ta l l iza t ion f rom ether. F i r s t a mixture of c rys ta ls deposited in the fo rm of white needles and cubes. The crys ta ls were fi l tered off and dried in a vacuum filter. On passage through a sieve, the acicular c rys ta l s were roughly separated f rom the cubic crys ta ls . By repeating these operations severa l t imes, (V) was isolated with mp 118-119 ~ and (I) with mp 125-126 ~ .

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Compgund (VI) with mp 164-165 ~ was obtained by careful ly following the published procedure [10], though this paper gives mp 176 ~ for it. Compound (IX) (rap 105-106.5 ~ was obtained in the same way as described previously for (X) [12], (XI) [13], (XII) [12], and (XIII) [14] f rom diethyl phosphite and benzyl methyl keto~e in the presence of C2H5ONa.

The It~ spect ra were taken on UR-10 and SP-100 instruments . The PMR spect ra were taken at a frequency o:~ 100 MHz on JNM--4H-100 and HA-100D spec t romete r s .

C O N C L U S I O N S

1. On the basis of the IR and NMR spect ra of the i somers obtained f rom N,N-diethylphosphoramidous and phenylphosphonous dichlorides and diacetone alcohol, these have been identified as configurational i somers , and the predominant conformations of the molecules have been determined for them.

2. Open-chain a-hydroxyalkylphosphonic compounds exist in the form of rotational i somers stabilized by an in t ramolecular H bond with the oxygen of phosphoryl or the hetero atom of the es te r grouping.

LITERATURE CITED

I. N.I. Rizpolozhenskii, Some Questions of Organic Chemistry [in Russian], Izd. Kazansk. Un-ta, Kazan' (1964), p. 122.

2. N.I. Rizpolozhenskii, F. S. Mukhametov, and R. R. Shagidullin, Izv. Akad. Nauk SSSR, Ser. Khim., 1121 (1969).

3. C.N.R. Rao, Chemical Applications of Infrared Spectroscopy, Academic Press, New York (1963). 4. R.A. Chittenden and L. C. Tomas, Spectrochim. Aeta, 22, 1449 (1966). 5. R. E. Sutton, Tables of Interatomic Distances and Configuration in Molecules and Ions, Special Pub-

licatic~n No. 11, Chemical Society, London (1958). 6. M. Tichy, Advan. Org. Chem., 5, 115 (1965). 7. C.D. Miller, R. C. Miller, and--W. Rogers, J. Amer. Chem. Soc., 80, 1562 (1958). 8. C. Benezza, S. Nseir, and C. Curisson, Bull. Soc. Chem. France, 1140 (1967). 9. R.N. Haszeldine, J. Chem. Soc., 1757 (1953).

10. K. Bergesen, Acta Chem. Scand., 23, 696 (1969). 11. J.H. Leteher and J. R. Van Wazer, Topics in Phosphorus Chemistry, 5, 169 (1967). 12. V.S. Abramov, Zh. Obshch. Khim., 22, 647 (1952). 13. V.S. Abramov and L. P. Semenova, Collection of Papers on General Chemistry [in Russian], Izd-

vo Al~:d. Nauk SSSR (1953), p. 391. 14. W.F. Barthel, P. A. Giang, S. A. Hall, J. Amer. Chem. Soe., 76, 4186 (1954).

1551