US3702831A - Nuclear magnetic resonance magnetometer solutions containing nitroxide free radicals having deuterium atoms - Google Patents

Nuclear magnetic resonance magnetometer solutions containing nitroxide free radicals having deuterium atoms Download PDF

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US3702831A
US3702831A US79977A US3702831DA US3702831A US 3702831 A US3702831 A US 3702831A US 79977 A US79977 A US 79977A US 3702831D A US3702831D A US 3702831DA US 3702831 A US3702831 A US 3702831A
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radicals
free radical
deuterated
nuclear magnetic
solvent
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Robert Chiarellier
Andre Rassat
Rene Besson
Antoine Salvi
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/24—Arrangements or instruments for measuring magnetic variables involving magnetic resonance for measuring direction or magnitude of magnetic fields or magnetic flux
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/24—Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Definitions

  • a magnetometer for measuring a weak magnetic field and its variations includes a solution which comprises a solvent with atomic nuclei (for instance protons) having non-zero magnetic moment and an organic hydrogenated free radical having unpaired electrons dissolved in the solvent.
  • the free radical comprises a nitroxide group, the nitrogen atom of which is exclusively linked to two carbon atoms each linked with three other carbon atoms.
  • a major portion at least of the hydrogen atoms of the free radical are deuterium atoms.
  • Radicals such as ditertiobutylnitroxide (DTBN) and radicals having a hexagonal heterocycle the heteroatom of which is nitrogen (for instance tetramethyl-2-2-6-6-aza-1-cyclohexanone-3- nitroxide 1) may be used.
  • the invention relates to polarization of atomic nuclei (protons in particular) of a solvent by electron pumping and to a nuclear magnetic resonance magnetometer of the type disclosed and claimed in US. Pat. specification No. 3,249,856 assigned to the assignee of the present invention.
  • the subject matter of said US. patent is incorporated in the present patent application by way of reference and some aspects of that earlier patent only will be repeated here.
  • U.S. Pat. No. 3,249,856 provides a complete description of a method for the dynamic polarization of the atomic nuclei of a solvent in which the magnetic moment and angular momentum of said nuclei are both difierent from zero; this method consists in dissolving in said solvent a free radical having unpaired electrons and exhibiting a hyperfine spectral structure with at least one electron resonance line of non-zero frequency in a zero magnetic field and in saturating said electron resonance line or lines of said free radical.
  • Said radical comprises a nitroxide group in which the nitrogen atom is additionally linked solely with two carbon atoms and these latter are each linked with three other carbon atoms.
  • di-tert-butylnitroxide also known as DTBN and having the formula:
  • the above-mentioned patent proposes in particular the use of triacetone amine nitroxide which is also known as tetramethyl-Z-Z- 6-6-aza-l cyclohexanone nitroxide-l and abbreviated to TANO, the formula of which is:
  • a hydrogenated free radical is used in which the greater part at least of the protons is replaced with deuterium nuclei.
  • FIGS. 1 and 2 are curves illustrating respectively the nuclear magnetic resonance spectrum of normal TANO and that of TANO in which the methyl groups are deuterated.
  • the initial stage of synthetic preparation of the deuterated TANO radical consists in the preparation of deuterated ammonia.
  • the following procedure can be adopted by way of example: 60 cm. of D 0 is caused to fall drop by drop onto 30 grams of magnesium nitride (approximately 0.3 mole). The reaction is highly exothermic. Ammonia which is evolved and charged with water vapor is passed into a column which is loaded with 20 g. of magnesium nitride (approximately 0.2 mole), then into two columns which are loaded with 3,702,831 a v v barytes so as to eliminate the residual water.
  • the ammonia gas is then condensed in traps which are immersed in a cooling mixture of acetone and solid carbon dioxide (-80 C.) and there are thus obtained 6 cm. of deuterated solid ammonia, namely approximately 4 grams (a yield of 40%).
  • the following stage that is to say the synthesis of the deuterated triacetoneamine, is then carried out as follows: 25 ml. (20 grams, 0.31 mole) of 99.7% deuterated acetone and 8 g. of a dehydrating and complexing agent such as calcium chloride are introduced in an autoclave which is then cooled in liquid nitrogen. There are then added 3.5 cm. of liquid ammonia ND (20.12 mole).
  • the calcium chloride assists the absorption of ammonia and, as a result of dehydration, the condensation of the acetone molecules.
  • the reaction product is then placed within a flask'provided with a coolant.
  • This product consists of two phases: a reddish liquid phase and a whitish phase of more or less pasty consistency.
  • This mixture is then heated to 70 C. for a period of five hours until the ammonia is completely evolved.
  • the two phases are now well separated from each other and the brown liquid phase is collected.
  • the triacetoneamine hydrate precipitates.
  • the triacetoneamine which is thus synthesized is purified by recrystallization followed by sublimation in vacuum, with the result that 5.1 g. of deuterated triacetoneamine are finally obtained.
  • the yield was 30% as calculated with respect to the starting acetone.
  • the last stage of the process is the preparation of triacetoneamine nitroxide in the deuterated form and this is carried out as follows: the 5.1 g. of deuterated triacetoneamine are dissolved in a few cm. of water or heavy water. There are then added 5.5 cm. of hydrogen peroxide having a strength of 110 volumes and approximately 100 mg. of phosphotungstic acid.
  • the reaction product is extracted with ether, washed with dilute sulphuric acid and then with water, then dried on sodium sulphate.
  • the ether is evaporated in vacuum.
  • the deuterated triacetoneamine nitroxide is then recrystallized in petroleum ether; the quantity obtained is 3.3 grams (yield: 60% as calculated with respect to the starting triacetoneamine).
  • the at positions of the carbonyl group are capable of rehydrogenating during oxidation by H 0 it is preferable to carry out on the substance obtained two consecutive isotopic exchanges in heavy water in a basic medium.
  • Complete deuteration of the methyl groups can be checked by obtaining a nuclear magnetic resonance spectrum of the product in which the at positions of the carbonyl group are hydrogenated; in this case, there is only one visible peak which corresponds to the resonance of the protons in the a position of the carbonyl group.
  • FIG. 1 shows the nuclear magnetic resonance spectrum of normal TANO. There are shown in these figures-two; peaks which correspond respectively to the hydrogens in the at position of the carbonyl group and to the hydrogens of the methyl groups.
  • FIG. 2 shows the nuclear magnetic resonance spectrum of deuterated TANO which is rehydrogenated in the at positions of the carbonyl group. There is now only one peak which corresponds to resonance of the protons which are present in the molecule.
  • magnetometer in which the apparatus can be employed will not be described here since said magnetometer can be of the type described in the main patent or, better still, of the type which is contemplated in French 'patent application No. EN 7027099 of July 22, 1970,
  • Deuterated DTBN is prepared by synthesis of deuterated nitro-tert-butane followed by action of metallic sodium on nitro-tert-butane in solution in dimethoxyethane (Hofimann method). The synthesis comprises four stages: v
  • a magnetometer for measuring a weak magnetic field and its variations, of the type including a solution which comprises a solvent with atomic nuclei having nonzero magnetic moment and dissolved in said solvent, an organic hydrogenated free radical having unpaired electrons, comprising a nitroxide group, the nitrogen atom of which is exclusively linked to two carbon atoms each linked with three other carbon atoms, the improvement consisting in that a major portion at least of the hydrogen atoms of the free radicals are deuterium atoms.
  • said radical includes a hexagonal heterocycle the heteroatom of which is nitrogen and is linked, on the one hand, to an oxygen atom with which it constitutes a nitroxide group and, on the other hand, exclusively with the two carbon atoms adjacent thereto in the hexagonal cycle, each of these two carbon atoms being linked on the other hand with two methyl groups.
  • hexagonal heterocycle radical is tetramethyl-2-2-6-6-aza- 1-cyclohexanone-3-nitroxide l.

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  • Physics & Mathematics (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • General Physics & Mathematics (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)
US79977A 1969-10-15 1970-10-12 Nuclear magnetic resonance magnetometer solutions containing nitroxide free radicals having deuterium atoms Expired - Lifetime US3702831A (en)

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FR6935278A FR2063416A6 (fr) 1969-10-15 1969-10-15

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US (1) US3702831A (fr)
BE (1) BE756934R (fr)
DE (1) DE2049799C3 (fr)
FR (1) FR2063416A6 (fr)
GB (1) GB1278213A (fr)
SE (1) SE365620B (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3915641A (en) * 1971-11-03 1975-10-28 Wisconsin Alumni Res Found NMR method for determination of enantiomeric compositions with chiral shift reagents
US3954410A (en) * 1972-11-21 1976-05-04 Merck Patent Gesellschaft Mit Beschraenkter Haftung Solvents for NMR spectroscopy
US4026953A (en) * 1972-11-21 1977-05-31 Merck Patent Gesellschaft Mit Beschrankter Haftung Solvents for NMR spectroscopy
US4863717A (en) * 1986-11-10 1989-09-05 The State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of The University Of Oregon Methods for circumventing the problem of free radial reduction associated with the use of stable nitroxide free radicals as contrast agents for magnetic reasonance imaging
US4866178A (en) * 1985-05-17 1989-09-12 Montedison S.P.A. Process for the preparation of 2-carboxypyrazine 4-oxides
US4889125A (en) * 1986-06-09 1989-12-26 Doddrell David M Method for the determination of iron stores in organic tissue and NMR spectrometer for performing this method
US5159269A (en) * 1989-06-14 1992-10-27 Commissariat A L'energie Atomique Process for the preparation of a radical cation salt and its use in an electron paramagnetic resonance (epr) magnetometer
US5258313A (en) * 1990-07-10 1993-11-02 Commissariat A L'energie Atomique Process for the detection or determination of oxygen by EPR spectrometry using radical lithium phthalocyanines and composition usable for in vivo determination
US5681753A (en) * 1994-12-07 1997-10-28 Commissariat A L'energie Atomique Solution containing a nitroxide radical for magnetometry by nuclear magnetic resonance

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2546518B1 (fr) * 1980-10-09 1986-08-01 Commissariat Energie Atomique Radicaux nitroxydes et leur procede de fabrication, application a la magnetometrie et a la gyrometrie
FR2531233A1 (fr) * 1982-07-29 1984-02-03 Mehier Henri Dispositif pour detecter et mesurer le gradient d'un champ magnetique
US4616182A (en) * 1983-11-09 1986-10-07 Technicare Corporation Nuclear magnetic resonance signal artifact removal

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3915641A (en) * 1971-11-03 1975-10-28 Wisconsin Alumni Res Found NMR method for determination of enantiomeric compositions with chiral shift reagents
US3954410A (en) * 1972-11-21 1976-05-04 Merck Patent Gesellschaft Mit Beschraenkter Haftung Solvents for NMR spectroscopy
US4026953A (en) * 1972-11-21 1977-05-31 Merck Patent Gesellschaft Mit Beschrankter Haftung Solvents for NMR spectroscopy
US4866178A (en) * 1985-05-17 1989-09-12 Montedison S.P.A. Process for the preparation of 2-carboxypyrazine 4-oxides
US4889125A (en) * 1986-06-09 1989-12-26 Doddrell David M Method for the determination of iron stores in organic tissue and NMR spectrometer for performing this method
US4863717A (en) * 1986-11-10 1989-09-05 The State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of The University Of Oregon Methods for circumventing the problem of free radial reduction associated with the use of stable nitroxide free radicals as contrast agents for magnetic reasonance imaging
US5159269A (en) * 1989-06-14 1992-10-27 Commissariat A L'energie Atomique Process for the preparation of a radical cation salt and its use in an electron paramagnetic resonance (epr) magnetometer
US5258313A (en) * 1990-07-10 1993-11-02 Commissariat A L'energie Atomique Process for the detection or determination of oxygen by EPR spectrometry using radical lithium phthalocyanines and composition usable for in vivo determination
US5681753A (en) * 1994-12-07 1997-10-28 Commissariat A L'energie Atomique Solution containing a nitroxide radical for magnetometry by nuclear magnetic resonance

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SE365620B (fr) 1974-03-25
GB1278213A (en) 1972-06-21
DE2049799B2 (de) 1978-11-02
DE2049799C3 (de) 1979-07-19
FR2063416A6 (fr) 1971-07-09
BE756934R (fr) 1971-03-16
DE2049799A1 (de) 1971-04-22

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