CA1268464A - Process for the weak field dynamic magnetic polarization of the nuclei of a solvent - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
The invention relates to nitroxide radicals and to their preparation process, applicable to magnetometry and gyrometry.
These nitroxide radicals have the developed formula:

Description

i 2 684~j~
-?-BACKGROU~D OF THE INVENTION
The present invention relates to free nitroxideradicals and their production process. These radicals, which are stable in solution, are used in magnetometry and gyrometry in weak magnetic fields, using nuclear magnetic resonance procedures with dynamic polarization of the nuclei of a solvent.
It is known that in earth's field magnetometers and gyrometers using nuclear magnetic resonance, the main problem is that of polarization, i.e. the-forced orientation of the spins, or the angular moment vectors of the nuclei, particularly protons of the solvent in which the radical is dissolved in an appropriate proportion.
This polarization can be obtained according to French Patent 1,174,136 entitled "Improvement to methods for measuring weak magnetic fields by magnetic resonance", filed on April 6th 1957 in the name of the present Applicant, by coupling the unpaired electron of a free radical, whose electronic paramagnetic resonance line is saturated by an appropriate high frequency field which has nuclei of the solvent.
The hitherto used free nitroxide radicals had a nitrogen 14 atom. Among these radicals are those having the following developed formula:

- B 7028.3 LC

. . : " : .
: , ,, , : .: ~ . :- :

D ~ D

In this formula, X represents D, Y represents D or OD or X and Y represent O bonded to the cycle of the radical by a double bond. The application to weak field magnetometry of deuterated 2,2,6,6-tetramethyl-4-piperidone-1-oxyl, currently called deuterate TANO, is described in French Patent

2,063,416 entitled "Polarization of the nuclei of a solvent by electronic pumping" filed in the name of the present Applicant on October 15th 1969.
In a high magnetic field (3000 Gauss), the diagram of the electronic levels of a l4N nitroxide ~ ¦
radical is such that three transitions are permitted giving-a hyperfine structure with three resonance lines.
In a very weakmagnetic field (below lO Gauss) the operational range of magnetometers, only two transitions are permitted. The resonant frequency of these transitions saturated to bring about the 25 dynamic polarization effect of the nuclei of the ~ ~
solvent is a function of different parameters ~ ~, ~nature of the solvent, nature of;the radical).
Moreover, the phase of the nuclear slgnal obtained by saturation of the "high line" is~in opposition to that obtained~by saturation of the "low line". This : ~: ' - :
.. . .
: : - ;, ~ .. . . . ...
- :, ,,.. ,-. , ' , ~:

- ~ ' - ', :

, .
.

~268~6 effect is utilized in gyrometer and magnetometer probes.
Such devices are described in French Patent 2,098,624, filed in the name of the present Applicant on July 22nd 1970 and entitlecl "Nuclear magnetic resonance magnetometer", as well as in a further French Patent 2,213,500~ filed in the name of the Applicant on September 20th 1972 and entitled "Process for measuring a rotation speed and gyrometer performing the same".
SUMMARY OF THE INVENTION
.
In order to increase the dynamic polarization coefficient of the nuclei of a solvent, particularly protons and consequently obtain an equal output signal with a reduced high frequency power, the invention envisages the replacement of nitrogen 14 by nitrogen 15 in nitroxide radicals of the type having the developed formula:

X~ y D ~ D
~1 I~D

O.
: 25 in which X represents D, Y represents D or OD and in which X and Y represent 0, bonded with the cycle of the radical by a double bond~
For simplification purposes throughout the :' .... ..

.: :: .

. ,,,. ~

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remainder of the text, the deuterated 2,2,6,6-tetramethyl-4-piperidone-1-oxyl radical, nitrogen 15, according to the invention will be called deuterated 15N TANO (TANO being the abbreviation of triacetonamine nitroxide); the deuterated 2,276,6-tetramethyl-piperidine-l-oxyl radical, nitrogen 15, according to the invention will be called deuterated 15N TANANE; whilst the deuterated 2,2,6,6-tetramethyl-4-piperidinol-1-oxyl, nitrogen 15, according to the invention will be called deuterated 1 N TANOL.
The diagram of the electronic levels of a nitrogen 15 nitroxide radical is such that in a high magnetic field only two transitions are permitted, giving a hyperfine structure with two resonance lines with a nitrogen 15 nuclear single electron coupling differing from the nitrogen 14 nucleus single electron coupling.
This offers several advantages in magnetometry and gyrometry. In particular, the ele~tronic spectrum in the very weak field is always composed of two lines. However, the latter are finer and of easier saturatDn, which leads to a significant energy gain.
Moreover, through the nitrogen 15 radicals and ~lvents this gives access to a different electronic resonant frequency range.
The invention also relates to the process for the preparation of the aforementioned nitroxide radicals, as well as théir application to magnetometry and gyrometry with nuclear magnetic resonance with dynamic polarization of the nuclei of a solvent.

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' ' '~ . . .

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BRIEF DESCRIPTION OF THE DRAWINGS
The invention is described in greater detail hereinafter relative to non-limitative embodiments and the attached drawings, wherein show:
Fig 1 the weak field resonance lines of the deuterated N TANO radical, i.e. the curve of the nuclear signal S as a function of the frequency ~ (expressed in megahertz - Fig la) and the deuterated 1 N TANO
radical (Fig lb) dissolved in methanol at a molar concentration 10 3.
Fig ~ diagrammatically, a magnetometer probe without a forbidden axis.
Fig 3 the high frequency power gain, i.e. the curve of nuclear signal S as a function of the high frequency power P(expressed in watt) for the deuterated 14N
TANO radical (Fig 3a) and the deuterated 1 N TANO
radical (Fig 3b).
DETAILED DESCRIPTION OF THE INVENTION
. . .
Fig la shows the weak field resonance lines of the deuterated 14N TANO radical and Fig lb the weak field resonance lines of the deuterated 15N
TANO radical, the two radicals being dissolved in a concentration of 10 3M in methanol. On the basis of these curves, it can be seen that the resonance lines of deuterated N TANO are finer and better resolved than those of deuterated 14N TANO and are consequently more easily saturated. This leads to a significant saturation power energy gain. In addition, there is a frequency displacement of the resonance lines.

:

- ,-. . -, -- . - :.:
,.. .. .
, , 8 ~

Thus, the range of polarization frequencies of the nuclei extends from 60 to 70 MHz for deuterated N TANO and 55 to 65 MHz for deuterated l~ TANO, as a function of the solvent used. Thus9 by using the "high line" of one of the two radicals and the "low line" of the other to obtain a more extensive "frequency crossing" range than when using only nitrogen 14 nitroxide radicals.
The increase in the frequency crossing range is advantageous in gyrometry, where working takes place in an artificially created field, the directive field, whose direction is that of the axis about which the rotation is measured. Thus, it is important that the earth's magnetic field is as small as possible compared with the directive field. For this reason, use is made of a directive field of min 2 Oersted (2.10 4 Tesla).
The nitrogen 15 nitroxide radicals can be advantageously used, like the nitrogen 14 nitroxide radicals, dissolved in most organic solvents not destroying the radical. The use of these radicals in water or in water doped with lithium chloride is also possible.
Fig 2 shows a probe of a magnetometer without a forbidden axis containing numerous elements described in French Patent 2,213,500.
Fig 2a is a diagrammatic section of a probe.
The probe comprises two similar assemblies 2 and 4, aligned along axis ZZ'. Each assembly comprises a coil 6,6' surrounding samples 8, 8'. The cross-section of '~

.

coils 6,6' can in particular be triangular. The samples are contained in two independent containers 10, 10', which can advantageously be shaped like two symmetrical bottles respecti~ely 14, 15 and 14', 15', in such a way that when juxtaposed they define a space in which coils 6, 6' can be arranged.
The exciting cavity resonator comprises a conductor 12 connected to the initial conductor of coaxial cable 13 and an outer envelope 18.
In uniaxial probes, like that shown in Fig ~2a,coils 6, 6' are wound in opposite directions, in such a way that the unwanted signals introduced there mutually compensate one another. However, the useful signals from the electromotive forces produced by nuclear resonance phenomena are summated. Such a winding procedure is shown in Fig 2b.
It should be noted that the above result is only achieved if the macroscopic resultant of the magnetic moments of the nuclei of one of the samples is opposite to the macroscopic resultant of the magnetic moments of the nuclei of the other sample.
In the illustrated embodiment, having a single very high frequency excitation source, it is necessary for these opposing effects to take place in response to an excitation occurring at the same frequency for the two samples.
In order to obtain such a result, it is possible to use e.g. a sample 8 constituted by deuterated 1 N TANo dissolved, at a molar concentration , in a solvent formed from 92% by volume dimethoxy .. ..

, ~ ": ; ; , , . .

,... ; ::, .. ... .. . .

ethane and 8% water and a sample 8' constîtuted by deuterated N TANO dissolved, at a molar concentration lO 3 in methanol.
In the case of such a magnetometer probe, it is the "high line" of sample 8 which is excited, whereas it is the "low line" of sample 8' which is excited.
The "frequency crossing" of these two transitions takes place for a 0.4 Oersted field with an electronic pumping frequency of 58.9 MHz.
In the case of magnetometer probes, through using nitrogen 15 nitroxide radicals according to the invention, it is possible to obtain a high frequency power gain, as illustrated by the curves of Fig 3.
Figs 3a and 3b respectively represent the nuclear signal S obtained at the terminals of coils 6, 6' of the probe, as a function of the high frequency power P, for the deuterated 14N TANO
radical and the deuterated N TANO radical. It can be seen that for the same value of the nuclear signal, the high frequency power value is lower for solutions containing deuterated 1 N TANO, which corresponds to a higher dynamic polarization co~
efficient of the nuclei of the solvent.
The processes for producing the deuterated N TANO, the deuterated 5N TANOL and the deuterated 15N TANANE~radicals will now be described.
These radicals are obtained from nitrogen 15 deuterated triacetonamine. This is obtained by reacting in the . .~, .
.. - : . .: :.
. . . :

...
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g presence of a dehydrating and complexing agent such as calcium chloride, deuterated acetone with ammonia, whose nitrogen is nitrogen 15 in accordance with the following reaction diagram:

o ~, CD3 15NH D~D

H

The nitrogen 15 deuterated triacetonamine obtained in this way is separated from the reaction mixture and then purified.
In an exemplified manner, information will be given on the operating conditions for obtaining nitrogen 15 deuterated triacetonamine~ 25g of acetone and 8g of calcium chloride are introduced into an autoclave, which is immersed in liquid nitrogen and placed under vacuum. 3.5cc of liquid 15N ammonia are introduced into it. After 48 hours - at 50C, the reaction product is placed in a 50cc round-bottomed flask and heated for 5 hours at 70C.
The red-brown liquid phase is then collected and to it is added 0.5cc of water. The nitrogen 15 deuterated triacetonamine hydrated obtained in this way precipitates on cooling the liquid to -15C, whilst vigorously stirring. The nitrogen 15 deuterated . - , .. . .

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triacetonamine is purified by sublimation. In this way, 15.lg are obtained, i.e. a 30% reaction yield.
The pure nitrogen 15 deuterated triacetonamine can also be obtained by chromatography of the red liquid on a neutral alumina column eluted by a mixture of ether and petroleum ether.
A description will now be given of the production of deuterated 1 N TANO and deuterated N TANOL radicals from nitrogen 15 deuterated triacetonamine.
The deuterated 15N TANO radical is produced by oxidizing nitrogen 15 deuterated triacetonamine with hydrogen peroxide in the presence of phosphotungstic acid. The deuterated lSN TANO radical is then extracted from the reaction mixture.
Thus, the obtaining of deuterated 15N TANO
radical can be represented by the following reaction diagram:
~

O :::

~ IO) ~ D
D3C 5 ~ 3 ~ D3C ~ 15 ~ CD3 I
~: O.

:~

.. . . . .

: . , . .~ :-:: , .
: :: : `~,;
.. -.. ..

6~4~

For example, details will be given of the operating conditions for obtaining the deuterated 15N TAN0 radical from nitrogen 15 deut~rated tri-acetonamine.
lg of nitrogen 15 deuterated triacetonamine obtained as described hereinbefore, lOmg of phospho-tungstic æ id and 1.5cc of hydrogen peroxide with 110 volumes are dissolved in 5cc of water. After reacting for 2 hours 9 ether extraction takes place of the deuterated N TAN0 radical. The organic phase is washed with normal sulphuric acid, then water and is then dried on sodium sulphate. The ether is evaporated and the radical recrystallized in petroleum ether. In this way, 0.75g of deuterated 15N TAN0 radical is obtained, i.e. a 75% reaction yield.
As certain methylenic deuteriums in " ~ "
of the ketone function have exchanged with protons during oxidation or extraction, an isotopic exchange in heavy water in a basic medium is necessary in order to obtain a total deuteration.
For this reason, the 0.75g of previouslY
obtained 15N TAN0 radical are dissolved in 20cc of heavy water, whose pH is raised to 13 by adding potassium carbonate. This solution is stirred for 2 hours at ambient temperature and then the radical is extracted with ether. The organic phase is dried on sodium sulphate and the ether evaporated.
The deuterated 15TANoL radical is prepared by reducing the ketone function~ the deuterated 15N

' ., .
, ~ . . .

~L~ ~ 8~ ~

TANO radical in anhydrous ethyl ether by lithium tetradeuteroaluminate. The reaction product obtained is hydrolyzed and then purified after being separated from the reaction mixture.
S The obtaining of deuterated N TANOL
radical can be represented by the following reaction diagram:

oll D ~ D
D ~ ~ D LiAlDD ~ ~ D

D ~ 15 ~ CD3 D3C ~ lS ~ CD3 O. O.

In an exemplified manner, details will be given of the operating conditions for obtaining the deuterated 15N TANOL radical from deuterated 15N
TANO.
To a s~ution of lg of deuterated 1 N TANO
in 200cc of anhydrous ethyl ether are added 140mg of lithium tetradeuteroaluminate. After reacting for 2 hours at oC~ hydrolysis takes place by the successive addition of lcc of water, lcc of 15~ soda solution and 3cc of water. The flocculent precipitate is filtered, the filtrate dried on sodium sulphate and the ether evaporated. The deuterated M TANOL radical is collected with a quantitative yield.
With regards to the preparation of deuterated .

-- - .
.. . . .
.. .
~, : :; ~
;. . ...

:. . .. .

12 ~ 8 TANANE, this takes place by reducing the ketone function of nitrogen 15 deuterated triacetonamine in deuterated diethylene glycol by deuterated hydrazine. Sodium is reacted on the product obtained, which makes it possible to obtain deuterated 2,2,6,6-tetramethylpiperidine.
The amino function of the deuterated 272,6,6-tetramethylpiperidine is then oxidized in ethyl ether by metachloroperbenzoic acid. Following neutralization of the acid, the deuterated N TANANE radical is extracted following its purification.
The obtaining of the deuterated 1 N TANANE
radical can be represented by the following diagram:

~ ~ ~D3 In an exemplified manner, information will be given on the operating conditions for obtaining the deuterated N TANANE radical.
The reduction of the ketone function of nitrogen 15 deuterated triacetonamine takes place in .--.. .

3L2~8~6 deuterated diethylene glycol by deuterated hydrazine, so thatit is previously necessary to deuterate the diethylene glycol and the hydrazine.
Preparation of the deuterated hydrazine:
A solution of 5g of hydrazine hydrated in lOcc of heavy water is refluxed for 12 hours, followed by distillation of the water. This exchange is repeated three times under the same condition.
Preparation of the deuterated diethylene glycol:
A solution of lOcc of diethylene glycol in lOcc of heavy water is refluxed for 12 hours and then the water is distilled. This exchange is repeated three times under the same conditions.
Obtaining nitrogen 15 1 N TANANE radical 2.5g of nitrogen 15 deuterated triacetonamine are added in small portions over 2 hours to a solution of 3g of deuterated hydrazine hydrate in lOcc of deuterated diethylene glycol, in a 50cc round-bottomed flask, equipped with a condenser and heated to 80C
on an oil bath. After 12 hours reaction, the condenser is replaced by a distillation bridge and the excess hydrazine and water are eliminated. This is fol~owed by the cold addition of 1.5g of sodium. The condenser is then replaced and the oil bath heated to 160C.
After 30 minutes, the nitrogen 15 deuterated 2,2,6,6-tetramethylpiperidine is sublimated and starts to deposit on the walls of the condenser. After 6 hours reaction, this gives 1.7g of nitrogen 15 deuterated 2,2,6,6-tetramethylpiperidine hydrate.
A solution of 1.5g of metachloroperbenzoic acid ;

. ~ . . ..
-.
:, . -,.

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in lOcc of ether is then added dropwise to a ~ution of lg of nitrogen 15 deuterated 2,2,6,6-tetramethyl piperidine hydrate in 20cc of ethyl ether. After reacting for 1 hour at 0C, th~e metachloroperbenzoic acid is neutralized by a 5N soda solution. The organic phase is washed with water and then with a few cc of lN sulphuric acid in order to ~extract the amine which has not reacted. This is followed by washing twice with water, drying on sodium sulphate and slow evaporation. This gives 0.62g of deuterated 1 N
TANANE radical3 i.e. a 71% reaction yield.

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- - , ~ .. . . .

Claims

WHAT IS CLAIMED IS:

1. A process for the weak field dynamic magnetic polarization of the nuclei of a solvent by saturation of an electronic magnetic resonance line of a free radical with a hyperfine spectral structure dissolved in said solvent in magnetometry and in gyro-metry, wherein the radical has the developed formula:
in which X represents D, Y represents D or OD, or in which X and Y represent 0, bonded with the cycle of the radical by a double bond.