NMR studies of barriers to rotation in N-nitrosamines

Spectrochmica

Acta,

Vol. 33A,

pp. 361 to 368.

NMR studies

Pergamon Press 1977.Printed

in Northern

Ireland

of barriers to rotation S. M.

in N-nitrosamines

GLIDEWELL*

Explosives Research and Development

Establishment,

Waltham Abbey, Essex

(Received 10 April 1976) Abstract-The potential energy barrier to rotation about the N-N bond in dimethylnitrosamine (I), N,N’ dinitroso hexahydro pyrimidine (III), and N,N’N” trinitroso hexahydro 1,3,5 triazine (IV) were determined by calculation of the lineshapes at different temperatures between 345 K and 515 K. An estimate of AG$ was made at coalescence for N-nitroso piperidine (II). The potential barriers increase in the order IV
calculation of the NMR absorption lineshape [12] for different rates until a fit is obtained with the observed lineshape at particular temperatures. An Arrhenius plot of rate and temperature is then used to determine the activation energy which is a measure of the barrier to rotation about the N-N bond. In this paper the effect of several N-nitroso groups in a molecule upon each other is investigated by determining activation parameters for rotation about the N-N bond in dimethylnitrosamine (I), N-nitroso piperidine (II), N,N’ dinitroso hexahydro pyrimidine (III) and N,N’,N” trinitroso hexahydro 1.3.5 triazine (IV).

The possibility of isomerism in N-nitroso compounds was first considered by HASZELDINE et ai. [ 1,2] and in some cases separation of the isomers has been effected [4-71. NMR spectra of Nnitrosamines were interpreted in terms of hindered internal rotation about the N-N bond by LOONEY, PHILLIPS and REILLY [3] and this means of isomeric interconversion is supported by the finding that, on the electron diffraction time scale, the skeleton of dimethylnitrosamine is planar [14]. The rate of interconversion of the isomers can be estimated by

0

Me\NNO Me’

0

N’

fi

ONN \/NNO

N ONN

A

NNO

g I

II

III

Previous determinations of the barrier to rotation in dimethylnitrosamine include those at 30 MHz [ 191 and 40 MHz [3] in which the published coalescence temperatures are mutually incompatible, a vapour phase determination [20] and a liquid phase determination at 60 MHz [21] over an unspecified temperature range. It is possible, though not necescarily desirable [22], for a simple case like Me?NNO, to estimate the rate of isomer intercon-

IV

version by approximate methods. These methods are, however, inappropriate for the more complex cases of III and IV and thus it was decided to repeat the determination of the activation parameters for dimethylnitrosamine so that comparisons between the different compounds could be made using results obtained by the same method. Incidentally, comparison of the results for dimethylnitrosamine obtained by the different methods could be made; some discrepancies occur in the case of rotation about C-N bonds in aryl nitrosamines

* Present Address: Department of Biological Sciences, University of Dundee, Dundee, DDl 4HN.

[231. 361

S. M.

362 MATERIALS

GLIDEWELL

AND METHODS

The spectra were recorded on a Perkin-Elmer RlO at temperatures between 193 K and 513 K and simultaneously recorded in digital form on paper tape using a Digiac CAT. I and II were studied as neat liquids, III in p-dichlorobenzene solution and 348 K and diIV in acetone up to isopropylacetamide at higher temperatures. For compounds I, III and IV the absorption spectrum was calculated and the input parameters varied until the best fit with the observed spectrum was obtained at each temperature. The lineshape in the presence of exchange between uncoupled spins is given by the expression [12]: I(w)=iRe(W.A-‘.

ambient temperature (306 K) consisted of two peaks of equal intensity at 63.8ppm and 63.0ppm corresponding to the methyls respectively lrans and cis to the oxygen [8-111. Appropriate conditions resolved each peak into a quartet due to H-H coupling which was confirmed by spin decoupling. The lineshape was calculated in terms of two sites and one lifetime, which latter parameter was varied in each case until a minimum value of the R factor [131= L(w,,,~-- w,,~~)~/L,(w~J was obtained. These R factors were in the range 0.03 to 0.10. An Arrhenius plot of In rate vs l/T was made weighting the points according to the inverse of their R factor and a least-squares best fit line drawn from which the pre-exponential factor and activation energy were calculated.

1) N-nifroso piperidine

where I(O) is the intensity of absorption at frequency W; W is a vector of the relative populations of the exchanging sites; A is a matrix with elements: 1 1 &&+p,, A mm’= i(o, -w)--T I Trill 2m 3 where w, is the chemical shift of site m; P,,. is the total probability of transitions occurring between sites m and m’; T,,, is the lifetime of site m; l/T,,,, is the contribution to the observed linewidth from all factors other than exchange. Plots of chemical shift and linewidth versus temperature for each compound showed a biphasic form-at low temperatures a small (sometimes zero) variation with temperature, and at higher temperatures, as exchange rates became appreciable, a much greater temperature dependence. Extrapolation of the low temperature parts of these plots allowed estimates of chemical shift and linewidth at higher temperature in the absence of exchange to be made, and these values were used in the calculations. Dimethylnitrosamine The proton

spectrum

of dimethylnitrosamine

at

The spectrum of N-nitroso piperidine showed a complex absorption with a maximum at S 1.8 ppm of relative intensity 3 and two multiplets each of relative intensity 1 centred at S4.2ppm and 63.8ppm. These low field peaks were assigned to the cy protons respectively trans and cis to the oxygen [8-111. Due to their complexity no lineshape was calculated but the rate of rotation about the N-N bond at coalescence (450 K) was estimated using the term ~rAu/2 for the rate [25]. Au, the frequency separation in the absence of exchange was estimated by extrapolation of a plot of the peak separation versus temperature which showed a positive gradient until the onset of coalescence. N,N’ dinitroso hexahydro pyrimidine At ambient temperature the spectrum of III showed a multiplet at S2.0ppm due to the r protwo multiplets centred on tons (see below), S4.4ppm and 63.8ppm due to the q protons respectively trans and cis to the adjacent nitrosyl oxygens and three singlets at 66.47, 65.92 and 85.43 ppm due respectively to the p protons of configurations A, B and C shown below. These

N+-‘--% p / ‘\o

0

NMR studies of barriers to rotation in N-nitrosamines singlets had partially coalesced at the highest temperature (408 K) for which the spectrum was recorded before decomposition became apparent. It

PA 1 _*_ PB 7.4

A=

i(“, -0)-E.

363

was assumed that rotation occurred sequentially and not simultaneously [12] thus allowing calculation of the lineshape in terms of three sites and two lifetimes using the matrix shown below:

1 PC _-T 1 -__.

1

TA

28

b-4

TC

PB 1 -.PC Tc i(oc-w)---T

l/Q

1

1

TC

where pa, pB and pc were the relative populations of the isomers A, B and C, determined from integrals at low temperatures and by extrapolation for the higher temperatures. The lifetime of the third isomer was derived from that for the other two and the activation parameters calculated as for dimethylnitrosamine. N,N’,N”

trinitroso hexahydro

Compound

1, 3, 5 triazine

IV can exist as two isomers:

and

E

D

I i(w,,-

w)-__-1 rcc

1

1

T *cc

27,

2C

The room temperature spectrum consisted of three broad (-3 Hz) singlets at 66.94, 86.32 and 6 5.69 ppm due respectively to protons tt, ct and ct’, and cc as shown above. On cooling to below 253 K, the centre peak was resolved into two peaks of similar intensity. The peak with intensity identical with that of the outer peaks was assigned to the protons ct of isomer E. Increasing the temperature caused the lines to broaden and coalesce to a single peak at 360 K. Making the same assumption about sequential rotations about the N-N bonds as for III, the matrix A was set up as shown below, in terms of four sites and one lifetime since there are only two isomers; x is the fraction of isomer D which remained essentially constant at 0.23. The activation parameters were calculated from an Arrhenius plot as before. Observed and calculated spectra at three temperatures are shown in Fig. 1. \

1

A= 1

1 27,,

\

l-x -6x

l-x 1 -6.x r,, RESULTS

AND

i(o,-o);=-T 1 rcc

DISCUSSION

The rates of rotation at a series of temperatures are shown in Tables l-3 for compounds I, III and IV respectively. The corresponding Arrhenius plots are in Figs. 2-4 and the activation parameters, including those for II, are in Table 4. The figures are quoted at 450 K which is the coalescence temperature for the (Y protons of II and thus the temperature to which the estimated AGf corresponds.

l-x -6x

1

1

Xl 1 ~,c

27,, i(o,8-w)+---

(x-l) 2x7,,

1 TM/

The value of 106 kJ mall’ for E, for dimethylnitrosamine is somewhat higher than the much quoted IOONEY, PHILLIPS and REILLY [3] figure of 96 kJ mol-’ which was determined by peak separation [24] over a small temperature range (25 K). BLEARS [21] used the ratio of maximum to minimum intensities to obtain a value of 105 kJ mall’ with the rather large estimated error of l 21 kJ mol-‘.

364

S. M. GLIDEWELL 294.2 K

t

00s

294.2 CALC

K

t.

343.2 K

343.2 K

415.2 K

OBS A

415.2 K CALC

FIG. 1. Observed and calculated spectra of N,N’,N” trinitroso hexahydro 343.2 K and 415.2 K. Table 1. Rate of rotation about N-N bond in dimethylnitrosamine T(K)

Rate (/set- ’ )

404.2 423.1 433.8 443.5 451.8 461.7 471.5 478.7 483.1 492.0 503.1 514.1

1.21 3.96 7.60 14.4 26.0 50.1 84.0 129.9 171.2 273.0 448.0 884.0

1,3,5 triazine at 294.2 K,

Only one value is quoted for the trinitroso compound, IV-the variation of the isomer ratio with temperature was negligible in comparison with the standard deviations of the ratio determinations. This indicates that the isomers have the same Ah;* and hence the same energy of activation. Statistically, isomer E is three times as likely as isomer D and the observed ratio of 3.3 *0.4: 1 is thus in accord with a value of -0 for AH* for the interconversion of the isomers. The case is slightly more complicated for the dinitroso compound, III. Here, the free energies of activation are identical within the experimental errors, indicating zero enthalpy of reaction for isomer

365

NMR studies of barriers to rotation in N-nitrosamines Table 2. Rate of rotation about N-N

bonds in NJ

dinitroso hexahydro pyrimidine

T(K)

Rate A(/sec- ‘)

Rate B(/sec-’ )

Rate C(/sec-‘)

364.2 373.6 383.3 393.6 398.3 403.2 408.3

1.31 3.15 5.86 16.4 20.7 32.8 40.6

2.03 5.39 9.58 25.8 33.2 51.1 66.8

1.86 4.55 8.70 21.6 29.0 41.4 61.7

Table 3. Rate of rotation about N-N bonds in N,N’,N” trinitroso hexahydro 1,3,5 triazine T(K)

Rate (/sec. ‘)

294.2 302.8 319.7 323.2 329.2 333.7 339.7 343.2 346.2 351.5 363.2 376.7 398.3 406.2 415.2 425.2

0.38 0.87 4.85 9.21 14.95 21.9 33.4 40.9 51.8 77.5 166.1 446.3 1143 2439 4447 7776

interconversion. Unlike IV however, the observed ratio of (4.7-3.3): (3.6-2.7): 1, is rather far from that of 1: 2 : 1 for A :B :C predicted on statistical grounds. The van? Hoff Isochore states that log, K = (-AH”/RZ-) + (AS”/R). Plots of -log, K versus l/T for A =B and B S C give values of 1.9 kJ mol-’ and -0 kJ mol-’ respectively for AH”. These values are no more than the estimated errors associated with the activation energies whose mutual similarity is thus consistent with the observed temperature dependence of the isomer ratio. The occurrence of the two isomers of IV in almost statistical ratio suggests that the cis-cis configuration of the nitroso groups cannot be as energetically prohibitive as the ratio 4 : 3 : 1, trans-tram : cisPans: cis-cis in III suggests. The answer must lie with the solvation energies of the different compounds. In the polar solvents used, solvation of the nitroso groups will occur and the greater the extent to which it occurs, the greater the entropy gain to the system. Access of solvent molecules to the nitroso groups will be facilitated in the trans-trans 8

T-lx

IO3

FIG. 2. Arrhenius plot for dimethylnitrosamine. configuration and hindered in the cis-cis configuration. In the case of isomer E of IV, the relative gain in entropy to the system by solvation of a trans-trans grouping is presurnably balanced by the relative loss (compared with the cis-trans case) engendered by solvation (or lack thereof) of a cis-cis grouping, so that the energies of solvation of D and E are very similar. In III, there is no possibility of such internal compensation and the greater entropy gain achieved by solvating a transtrans grouping is shown in the relative populations of the three isomers. This point illustrates the need to consider the solute/solvent system as a whole and not just the solute in isolation. It can be seen that while the number of nitroso groups in a ring affects the barrier to rotation about the N-N bond, the initial relative configurations do not. This is contrary to the results of order of

366

S. M.

GLIDEWELL

J J× ~E ×J×

J

×f

J

2E c~

<

N c~

a-l.DJ U-I

.o Re-

~

J

N

N a .o

~

e~

Z

z~E

×J× J ~

<

"3 I

~"0

o~

I

I

I

.6

I o

a~.DJ

l.J"I

co a~

"0 M

al

J c~

~

•

f × J × J

,,

_~.~ e~

< 1

I

I

a4-oJ u3

]

I

367

NMR studies of barriers to rotation in N-nitrosamines

magnitude calculations of dipole-dipole interactions in dimethylnitrosamine [14,15] which indicate an electrostatic repulsion between mutually cis nitroso groups of 12 kJ mol-’ which might be manifested as a lower activation energy for the cis-cis isomer. It also seems unlikely that ring strain is the cause of the differences since the values of AG’ for dimethylnitrosamine and N-nitroso piperdine are probably not significantly different in view of the approximate value of AG+ for N-nitroso piperidine. This is supported by studies of molecular models [16] in which rings made from tetrahedral carbons and planar trigonal nitrogens show no more strain than cyclohexane. It is concluded that the origin of the differences in the barrier to rotation about the N-N bonds in these compounds is electronic in nature. The high barrier to rotation in N-nitroso compounds is normally explained in terms of the resonance hybrid structures: FIG. 4. Arrhenius

plot for N,N’,W 1,3,S triazine.

trinitroso

Table 4. Activation Compound Me,NNO

0

hexahydro

parameters

E,(/k.I mol-‘)

of nitrosamines

A(/sec~ ‘) 4x lOI

106i4

-

NNO

at 450 K AG:,,,(/kJ 97.0*

mol-‘) 1.7

93.0

c

r---l “\,/“v”\,p

98.0*3.3

1.4 x 10’4

8.5.azt3.3

98.0rt3.3

2.3 x lOI

83.O~t3.3

97.0*

1.7

1.6x IO”

83.5+2.1

76.4+

2.4

1.7 x 1o13

71.6zt2.5

0

A

ONN,,NNO

368

S. M. GLIDEWELL

The

presence

(which will

an

the

has a barrier

form

G, then there another,

a state

Either

observed

in

pyrimidine

of the

piperidine) > trinitroso

corresponding

of

un-

in the

ring

in-

predicts to

rotation

hexahydro 1,3,5

resonance

triazine of

hybrid.

explanation

comes

from

due to vNNN and vNo. A decrease of resonance

vNN to

and

form

vNo to

G will cause

increase.

Observed values [18] are 1096cm-‘, 1060cm-‘, 1040cm-’ for vNN and 1424 cm-‘, 1471 cm-‘, 1505 cm-’ for vNo in N-nitroso piperidine, dinitroso hexahydro pyrimidine and trinitroso hexahydro 1,3,5 triazine respectively, all in dibromomethane as solvent. SUMMARY Protons groups

bonded

have

whether rrans

to carbon

different

they

(resonating

at

higher

As the temperature

rotation

about

until,

tained, The lated

a single and

complex

a measure temperature

rate vs inverse

the activation

field)

bond

energy

according

at lower to

is raised

the

to

field)

or

nitrosyl

from ambient,

interconverts

these

high temperature

is at-

“averaged”

intermediate

particular log,

the N-N

if a sufficiently

to N-nitroso

shifts

lie cis (resonating

oxygen. sites

adjacent

chemical

resonance lineshapes

of the

rate

obtained. temperature

is observed. can be calcu-

of rotation Arrhenius

at a

plots of

lead to a value for

of the rotation

in the ring increased from one to three. The initial relative configuration of the nitroso groups did not affect the activation energy and it was concluded that the electron withdrawing effect of the nitroso groups was responsible. Acknowledgements-1 should like to acknowledge the excellent technical assistance of Mrs. P. E. FULLER and Drs. R. L. WILLIAMSand R. K. HARRIS for much helpful discussion.

the

in the contribution

in the prevalence decrease

increasingly

Ns

hexahydro

this

of

close

> dinitroso

G to the nitrosamine

Corroboration

were

charges

dimethylnitrosamine

to a decrease

the i.r. absorptions

Alterna-

in a ring

barrier

order

the

(Cl&NNO

approaches

that

the

(- N-nitroso

kJ mol-‘.

of affairs

at R

hence

-20

be positive

these

sequence

decreases

and e.g.

number

of

G

groups

would

as the

creases.

form

nitroso

group

moiety)

N-N,

of only

if all the

favourable

of

about

tively,

withdrawing

containing

prevalence

to rotation

to one

electron

be a nitroso

reduce

barrier [17]

of

could

process. Comparison of the free energies of activation, AG,&, for the compounds dimethylnitrosamine, N-nitroso piperidine, N,N’ dinitroso hexahydro pyrimidine and N,N’,N” trinitroso hexahydro 1,3,5 triazine showed that inclusion of the nitroso group in a six-membered ring had no effect but the barrier to rotation decreased as the number of nitroso groups

REFERENCES [l] R. N. HASZELDINEand J. JANDER, J. Chem. Phys. 23, 979 (1955). [2] - and B. J. H. MATSON, J. Chem. Sot. 4172 (1955). [3] C. E. MOONEY,W. D. PHILLIPSand E. L. REILLY, J. Am. Chem. Sot. 79, 6136 (1957). [4] A. MANNSCHRECK, H. MUENSCHand A. MATTHEUS, Annew. Chem. Int. Ed. (Enn), 5, 728 (1966). [5] A. MANNSCHRECKand H.-MIJ&SCH: ibid; 6, 984 (1967). [6] A. MANNSCHRECK, A. MATTHEUSand G. RISSMEN,J. Mol. Spec. 23, 15 (1967). [7] A. MANNSCHRECKand H. MUENSCH, Tetrahedron Letl. 3227 (1968). [8] G. J. KARABAT~OSand R. A. TALLER, J. Am. Chem. Sot. 86, 4373 (1964). [9] H. W. BROWN and D. P. XOLLIS, J. Mol. Spec. 13, 305 (1964). [lo] R. K. HARRIS and R. A. SPRAGG, ibid, 23, 158 (1967). [ll] T. AXENROD and P. S. PREGOSIN,Chem. Comm. 702 (1968). [12] A. ABRAOAM, The Principles of Nuclear Magnetism, O.U.P. Oxford (1961). r131_ W. C. HAMILTON. Staristics in Phvsical Science. _ ’ Ronald Towcester, U.K. (1964). [14] P. RADEMACHER and R. STOLEVIK, Acta Chem. Stand. 23, 660 (1969). [15] D. L. HAMMICK,R. G. A. NEW and L. E. SU ITON, J. Chem. Sot. 742 (1932). [16] A. S. DREIDING,Helu. Chim. Acta 42, 1339 (1959). [17] S. ANDREADAS, J. Org. Chem. 27, 4163 (1962). [18] R. L. WILLIAMS, Personal communication. [19] W. D. PHILLIPS,C. E. LOONEY and C. P. SPAETH,J. Mol. Spec., 1, 35 (1957). [20] R. K. HARRIS and R. A. SPRAGG, Chem. Comm. 362 (1967). [?l] D. J. BLEARS, J. Chem. Sot. 6256 (1964). [22] A. ALLERHAND, H. S. GUTOWSKY,J. JONAS and R. A. MEINZER, J. Am. Chem. Sot. 88, 3185 (1966). [23] P. D. BUCKLEY, A. K. FURNESS, K. W. JOLLY and D. N. PINDER, Aust. J. Chem. 27, 21 (1974). [24] H. S. GUTOWSKYand C. H. HOLM, J. Chem. Phys. 25, 1228 (19.56).