New cascade syntheses of nitronyl nitroxides and a new synthetic approach to imino nitroxides

FULL PAPER

DOI: 10.1002/ejoc.200801237

New Cascade Syntheses of Nitronyl Nitroxides and a New Synthetic Approach

to Imino Nitroxides

Eugene Tretyakov,^[a]Svyatoslav Tolstikov,^[a]Aleksander Mareev,^[b]Alevtina Medvedeva,^[b]

Galina Romanenko,^[a]Dmitry Stass,^[c]Artem Bogomyakov,^[a]and Victor Ovcharenko*^[a]

Keywords: Nitrogen heterocycles / Radicals / Nitronyl nitroxides / Imino nitroxides / Cascade reactions / Alkynes

Suspensions of M_xO_y(MnO₂, Co₂O₃, Ni₂O₃) in protic solvents

(MeOH, EtOH) have been found to be suitable systems for

use in a cascade transformation of 4,4,5,5-tetramethyl-2-[2-

(trimethylsilyl)ethynyl]imidazolidine-1,3-diol (1a) into 2-eth-

ynyl-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl 3-

oxide (3). In MnO₂/MeOH, the products of further transfor-

mation of 3, (Z)- and (E)-2-(2-methoxyvinyl)-4,4,5,5-tet-

ramethyl-4,5-dihydro-1H-imidazole-1-oxyl 3-oxides, were

obtained by the regiospecific addition of MeOH to the triple

bond of 3. In the reaction in MnO₂/MeOH+H₂O (1:1), the Z

isomer was the sole product. A multistep one-pot transforma-

tion of 1 into 4,4,5,5-tetramethyl-2-[2-oxo-1-(4,4,5,5-tetra-

methylimidazolidin-2-ylidene)ethyl]-4,5-dihydro-1H-imid-

azole-1-oxyl 3-oxide occurred in MnO₂/EtOH. For (E)-2-[2-

(diethylamino)vinyl]-4,4,5,5-tetramethyl-4,5-dihydro-1H-

imidazole-1-oxyl 3-oxide, it was shown that use of the MnO₂/

secondary amine system provided a one-pot transformation

of 1a and gave (E)-aminovinyl-substituted nitronyl nitroxide

as the sole product. In combined MnO₂/ROH/K₂CO₃systems

(R = Me, Et), the imidazolidine-1,3-diol 1a was transformed

into (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-4,5-dihydro-

1H-imidazole-1-oxyl 3-oxide and the acetals 2-(2,2-dimeth-

oxyethyl)- and 2-(2,2-diethoxyethyl)-4,4,5,5-tetramethyl-4,5-

dihydro-1H-imidazole-1-oxyl 3-oxide. In MnO₂/MeNO₂we

obtained the products of the transformations of different 2-

substituted 4,4,5,5-tetramethylimidazolidine-1,3-diols (R =

CϵC–SiMe₃, aryl, hetaryl, alkyl) or nitronyl nitroxides into

the corresponding imino nitroxides (13 products); this reac-

tion is a new method for the preparation of imino nitroxides

and allowed us to synthesize the first α-acetylenyl-substi-

tuted imino nitroxides. The majority of paramagnetic com-

pounds, including the derivatives of 1a, were obtained as

perfect crystals, and their structures were determined by X-

ray structure analysis (14 solved structures).

Germany, 2009)

tives of nitronyl and imino nitroxides were inaccessible

compounds; their precursors each contained a combination

of an N–OH group and a triple bond, rearrangement of

which led to the aminoenone fragment,^[5]also formed in

reactions between 4,4,5,5-tetramethyl-4,5-dihydro-1H-imid-

azole-3-oxides and activated alkynes.^[6,7]Thanks to the dis-

covery of the cascade reaction between 1a and PbO₂in

MeOH, leading to 2-ethynyl-4,4,5,5-tetramethyl-4,5-dihy-

dro-1H-imidazole-1-oxyl 3-oxide (3), however, compound 3

became accessible and could be used in various transforma-

tions.^[8]To study the synthetic potential of the cascade reac-

tion here, we concentrated on how the heterophase oxi-

dation of 1a could be changed by varying the oxidant, reac-

tion time, and protic and aprotic polar and low-polar sol-

vents. Here we wish to report the results of these studies,

extending the available preparative scope of nitronyl and

imino nitroxide chemistry.

Introduction

Nitronyl nitroxides (NNs) and imino nitroxides (INs)^[1]

are member compounds of the unique class of persistent

organic paramagnets, widely used in the design of molecu-

lar magnets,^[2]paramagnetic materials with giant ther-

mostriction,^[3]and contrastive substances for magnetic reso-

nance tomography.^[4]Interest in specially designed nitronyl

and imino nitroxides has dramatically increased, which has

stimulated the development of procedures for the synthesis

of the key derivatives of nitronyl and imino nitroxides (e.g.,

α-ethynyl derivatives), leading to wide series of desired poly-

functional derivatives. Until recently, the α-acetylene deriva-

[a] International Tomography Center, Siberian Branch, Russian

Academy of Sciences,

Institutskaya Str. 3a, 630090 Novosibirsk, Russian Federation

Fax: +7-383-3333455

E-mail: Victor.Ovcharenko@tomo.nsc.ru

[b] A. E. Favorsky Institute of Chemistry, Siberian Branch, Russian

Academy of Sciences,

Results and Discussion

Favorsky Str. 1, 664033 Irkutsk, Russian Federation

[c] Institute of Chemical Kinetics and Combustion, Siberian

Branch, Russian Academy of Sciences,

M_xO_y(MnO₂, Co₂O₃, Ni₂O₃)/Protic Solvent System

Institutskaya Str. 3, 630090, Novosibirsk, Russian Federation

Supporting information for this article is available on the

WWW under http://ww w .eurjoc.org/ or from the author.

Experiments performed under normal conditions showed

that after the addition of excess MnO₂, Co₂O₃, or Ni₂O₃to

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Eur. J. Org. Chem. 2009, 2548–2561

Nitronyl Nitroxides and Imino Nitroxides

a solution of 1a in MeOH or EtOH, the reaction mixtures

The maximum yield of 3 was isolated when excess M_xO_y

became deep dark violet after a minute, as was also the case was used; in this case, 1a was completely converted in

in the previously described reaction of 1a in MeOH in the 30 min. Use of stoichiometric ratios of ν(M_xO_y)/ν(1a) was

presence of PbO₂. Spin-labeled acetylene 3 was then less effective for the synthesis of 3. At ν(MnO₂)/ν(1a) =

quickly^[8]isolated from the reaction mixture (Scheme 1). 3:1,^[10]for example, complete oxidation of 1a required

According to TLC data, other products formed in relatively longer times, and product 3 was obtained in much lower

small amounts over this time (Entries 1–3, Table 1), and 3 yields because of its further transformation into 4a·H₂O,

was obtained in a high yield (ca. 60–85%). Compound 3 5a, and 6a (Scheme 1, Entries 5 and 6, Table 1). We exam-

also formed quickly under special conditions: namely, in ined these transformations and found that higher reaction

absolute EtOH and under a dry atmosphere. At the same times decreased the yield of 3, generally increased the con-

time, an authentic sample of 2a^[9]did not change in the tents of 4a·H₂O and 5a in the reaction mixture, and led to

presence of MnO₂, Co₂O₃, or Ni₂O₃over the first 20 min. other products, with the product ratios depending on the

Consequently, the fast formation of 3 after treatment of 1a ν(M_xO_y)/ν(1a) ratio and the solvent used. Thus, at

with M_xO_yindicated that the basic reagent, responsible for ν(MnO₂)/ν(1a) ≈ 15:1, the reaction between 1a and MnO₂

splitting the Si–C bond, appeared during the course of the in MeOH over 24 h mainly led to the cis isomer 4a·H₂O,

reaction. It can be assumed that the reduction of MnO₂, the trans isomer 5a, and compounds 6a and 7 in low yields

Co₂O₃, or Ni₂O₃gives the corresponding hydroxides, and (Entry 9, Table 1). If the reaction was performed in a mix-

that these cause ionization of solvent molecules into RO^–ture of equal volumes of MeOH and H₂O at the same

ions, the concentrations of which are high enough for fast ν(MnO₂)/ν(1a) ratio, the major product was 4a·H₂O,

solvolysis of the Si–C bond. If so, larger radicals R should whereas the content of 5a was low and that compound was

impede this reaction because the approach of RO^–to the not isolated (Entry 8, Table 1). The yields of 4a·H₂O and

sterically crowded Si–C bond should be hindered. Indeed, 5a obtained in the above experiments proved to be maxima

the reaction between MnO₂and 1a in tBuOH mainly gave and decreased when the stoichiometric ν(MnO₂)/ν(1a) ratio

2a in a 76% yield (Entry 4, Table 1). The interaction of the was used or when other oxidants were used at different

imidazolidine-1,3-diol 1a with MnO₂, Co₂O₃, or Ni₂O₃(as ν(M_xO_y)/ν(1a) ratios (Entries 7, 12, 14, 16; Table 1), or

well as with PbO₂) in MeOH or EtOH was therefore a cas- when the reaction time was varied.

cade reaction. Its first stage was the oxidation of 1a, ac-

The reaction between 1a and MnO₂in EtOH gave a mix-

companied by the simultaneous generation of a base, and ture of 3, 4b–6b, and 7. The product ratio changed as the

because of this the second stage was the removal of the reaction time increased. After 60 h, the reaction mixture

Me₃Si group, finally forming compound 3.

mainly contained 7, which was formed in a 34% yield when

the initial reagent ratio was ν(MnO₂)/ν(1a) = 3:1 (En-

tries 10, and 11 in Table 1).

The distinctive feature of the cascade reaction between

1a and M_xO_yin MeOH was thus the regiospecific addition

of MeOH molecules to the triple bond in 3, which occurred

after the splitting of the C–Si bond (i.e., the cascade reac-

tion involved one more stage). Products 4a·H₂O and 5a,

which formed under one-pot synthesis conditions, proved

to be kinetically stable in MnO₂/MeOH and were obtained

in satisfactory yields. When the cascade reaction was per-

formed in EtOH, the rate of the transformation of 3 into

4b and 5b was lower than that of the similar transformation

in MeOH. The composition of the reaction mixture there-

fore depended strongly on decomposition, indicated by the

formation of 4,4,5,5-tetramethyl-2-[2-oxo-1-(4,4,5,5-tetra-

methylimidazolidin-2-ylidene)ethyl]-4,5-dihydro-1H-imid-

azole-1-oxyl 3-oxide (7). Previously, aminoenal 7 had been

prepared by treatment of 3 with 4,4,5,5-tetramethyl-4,5-di-

hydro-1H-imidazole 3-oxide (8a).^[11]On this basis, it is rea-

sonable to assume that under the reaction conditions, 3 was

gradually reduced to 2-ethynyl-4,4,5,5-tetramethyl-4,5-dihy-

dro-1H-imidazole 3-oxide (8b); by analogy with 8a, this was

then involved in 1,3-dipolar cycloaddition at the triple bond

of 3 to form intermediate A, which rearranged into 7

(Scheme 2).

Compounds 6a, 5b, and 6b, formed in small amounts in

the oxidation of 1a with M_xO_y, were identified by compari-

son of their IR spectra, R_fvalues, and spot colors (TLC)

Scheme 1. Reactions between 1a and M_xO_yin ROH (for details,

see Table 1).

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Table 1. Identified products of the reactions between 1a and M_xO_yin ROH.

Entry

[Ox]

ROH

ν(M_xO_y)/ν(1a) Time [h]

Identified products (% isolated yield)^[a]

1

2

3

4

5

6

7

8

MnO₂

Co₂O₃

Ni₂O₃

MnO₂

PbO₂

MeOH or EtOH

MeOH

tBuOH

MeOH

MeOH/H₂O 1:1, v/v ≈15:1

MeOH

EtOH

≈15:1

≈8:1

0.2–0.5

0.2–0.4

0.2 or 6

0.4

3 (80–85)

3 (60–75)

3 (60–80)

2a (76)

4a·H₂O (+)

3 (+)

5a (+)

≈8:1

≈15:1

3:1^[b]

3 (46)

1a (+)

6^[c]

3 (32)

4a·H₂O, 5a, 6a (+)

5a (6)

5a (+)

5a (22)

26^[d]

4a·H₂O (18)

4a·H₂O (67)

4a·H₂O (46)

4b–6b, 7 (+)^[e]

7 (34)

6a (+)

18^[d]

9

≈15:1

3:1^[b]

5:1

20^[d]

6a (4), 7 (+)

10

11

12

13

14

15

16

50^[d]

EtOH

60^[d]

4b–6b (+)

5a (14)

5a (18)

MeOH

24^[d]

4a·H₂O (11)

4a·H₂O (12)

4a·H₂O, 5a (+)

[f]

PbO₂

3:2^[b]

≈8:1

3:2^[b]

≈8:1

28^[d]

6a (+)

Ni₂O₃

Co₂O₃

70^[d]

20

50^[d]

4a–6a (+)^[e]

[a] The “+” symbol denotes that, according to TLC data, the product was present in the reaction mixture in relatively small amounts

and was not isolated. [b] The stoichiometric ratio ν(M_xO_y)/ν(1a). [c] The total consumption time of 1a. [d] The total consumption time

of 3. [e] Unidentified products formed in addition to 4–7. [f] Products 2–7 were not detected.

reaction gave a slightly increased yield of 6b, whereas the

content of 7 in the reaction product was comparable to that

of 4b·H₂O. The hydrate 4b·H₂O was obtained several times

as a solution by preparative chromatography, but evapora-

tion of the solution and all attempts to crystallize the resi-

due from hexane led to the formation of a mixture of

4b·H₂O and trans isomer 5b. This indicated that 4b·H₂O

Scheme 2. Possible mechanism for the formation of 7.

was more readily dehydrated than 4a·H₂O because of the

increased size of the alkyl substituent; the product, cis iso-

mer 4b, was also unstable and isomerized into 5b even un-

der mild conditions (this actually gave satisfactory yields of

5b.) Heating of 5b by itself at 50–60 °C in EtOH in the

presence of K₂CO₃(7 h) gave acetal 6b with a 52% yield.

In view of the behavior of 3 in EtOH/K₂CO₃at 50–60 °C

described above, this is indirect evidence that neither

4b·H₂O nor 4a·H₂O added an EtOH molecule in the pres-

ence of K₂CO₃. Therefore, if 6b is the target product, it is

much more convenient to stir a ready-made ethanol solu-

tion of 3 at 20–25 °C in the presence of KOH (10 h). As in

the case of K₂CO₃, a mixture of 5b and 4b·H₂O, with the

latter dominant, initially formed under these conditions

(TLC data); in the presence of a stronger base, however, not

only 5b, but also 4b·H₂O, transformed into acetal 6b (cis

isomer 4b·H₂O reacted much more slowly than 5b). This

ensured that the four stages of the transformation of 1a into

6b could be performed without isolation of intermediate ni-

troxides (the yield of 6b reached 33%).

with those of authentic samples. For their preparation we

used a MnO₂/ROH/K₂CO₃combination, which involved

the cascade reaction for the synthesis of 3. Thus, in MeOH

in the presence of K₂CO₃, nitroxide 3 was completely trans-

formed into 4a·H₂O and 5a after 1 h and into 4a·H₂O and

6a after 24 h. In the course of these experiments, we came

to believe that the acetal 6a was formed exclusively from

trans isomer 5a, and this prompted a series of additional

experiments. At room temperature, unaccompanied 4a·H₂O

in MeOH in the presence of K₂CO₃did not change for at

least 4 h, whereas the trans isomer 5a was quantitatively

transformed into 6a under the same conditions.

Remarkably, solid 4a·H₂O held its water molecule so

tightly that did not lose it after recrystallization, SiO₂

chromatography (4a·H₂O has a much lower R_fthan 5a), or

drying in vacuo. Attempts to perform dehydration of

4a·H₂O under more rigid conditions, however, led to the

formation of 5a (along with the decomposition products).

It was appealing to expand the potential of this one-pot

All this indicated that 4a·H₂O existed as a stable hydrate, synthesis of nitronyl nitroxides from 1a by performing it in

4a·H₂O_Solv, both in the solid state and in solution. The in- amines, which were chosen from a range of radically dif-

ertness of 4a·H₂O_Solvrelative to 5a in MeOH/K₂CO₃as de- ferent representatives of this class of compounds. Dihydrox-

scribed above could then be explained by the water mole- yimidazolidine 1a was thus treated with 15-fold excesses of

cule held by the cis isomer blocking the attack on the MnO₂in different amines (Et₂NH, nBuNH₂, or tBuNH₂)

double bond by the MeO^–anion.

at 20 °C (Scheme 3). Under these conditions, 1a was com-

In EtOH/K₂CO₃, the time needed for the consumption pletely transformed into 3 in 5–10 min. Further transforma-

of 3 increased to 50 h, and a mixture mainly containing tions of 3 depended on the amine solvent. In Et₂NH or

4b·H₂O, as well as 5b, 6b, and 7, formed. At 50–60 °C, the nBuNH₂a greenish blue product had formed after 1.5–2 h

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Eur. J. Org. Chem. 2009, 2548–2561

Nitronyl Nitroxides and Imino Nitroxides

(major product, TLC data). The diethylaminovinyl-substi-

tuted nitroxide 9a was isolated in ca. 90% yield. An attempt

to isolate 9b showed that this nitroxide was unstable and

quickly decomposed during concentration of its solution.

In tBuNH₂, 3 was transformed into a crimson-colored

product, which gave colorless 10 during its isolation. The

oxidation of 1a with MnO₂in sterically uncrowded RRЈNH

or RNH₂thus makes it possible to perform three stages in a

one-pot synthesis to prepare diethylaminovinyl-substituted

nitronyl nitroxides.

Figure 1. a) Molecule and b) crystal packing in 4a·H₂O.

Scheme 3. Reactions between 1a and MnO₂in amines.

by a square pyramid with one of the O_hfacatoms at the

apex [Cu(2)–O_hfac2.219(4) Å] and the O(2s) atom of the

second N–O group of the bridging nitroxyl and three O_hfac

atoms [Cu(2)–O_hfac1.925(4)–1.960(4) Å and Cu(2)–O(2s)

2.003(3) Å] at the base. The pyramid is completed to an

elongated octahedron by the O(2sЈ) atom, lying at a dis-

tance of 2.538(4) Å; this leads to the formation of chains in

the structure of the complex (Figure 2, b). The N–O dis-

tances in coordinated 5a differ significantly – N(1s)–O(1s)

1.277(5) Å and N(2s)–O(2s) 1.310(5) Å – because of the dif-

ferent modes of their coordination to Cu^IIions. In mole-

cules of 5a, the angle between the planes of the C(8s)C(9s)-

O(3s) and N(1s)C(7s)N(2s) fragments is 11(1)°, which leads

to more effective π conjugation than in 4a·H₂O, in which

this angle is 44(1)°. As a consequence, the C(9s)–O(3s) and

O(7s)–C(8s) bond lengths are smaller [1.326(6) Å and

1.404(7) Å, respectively] than the similar bonds in 4a·H₂O.

The replacement of MeO by EtO led to crystallization of

The structures of the products were supported by X-ray

structure analyses (see Supporting Information), by satis-

factory C, H, and N microanalyses, and by high-resolution

mass spectroscopy. The compounds were also characterized

by IR and ESR spectroscopy and magnetochemical mea-

surements.

Discussion of the X-ray data can start with the group

consisting of 4a·H₂O, 5a, and 5b, which are the first alk-

oxyvinyl-substituted nitronyl nitroxides. For 4a·H₂O (Fig-

ure 1), the X-ray study revealed short C(9)–O(3)

[1.339(6) Å] and C(7)–C(8) [1.446(6) Å] bond lengths, which

are indicative of substantial conjugation in the side frag-

ment.^[12]In the nitronyl nitroxide fragment, the N(1)–O(1)

bond length [1.290(4)] is slightly larger than N(2)–O(2)

[1.280(4) Å] because of O(1) being involved in H-bonding

with water molecules [the O···O distances are 2.870(7) and

2.872(7) Å] (Figure 1, b).

After recrystallization, nitronyl nitroxide 5a was always 5b in the form of perfect needles from hexane. An X-ray

isolated from mother solutions in the form of an oil, which study of a selected single crystal showed that 5b, like coordi-

gradually solidified into an amorphous phase. It crys- nated 5a, had effective conjugation between the side and

tallized only as a trinuclear complex with copper(II) hexa- nitronyl nitroxide fragments. This is confirmed by the rela-

fluoroacetylacetonate [Cu(hfac)₂]₃(5a)₂, isolated as green tively short^[12]C(7)–C(8), C(8)–C(9), and C(9)–O(3) bond

plate-like crystals by slow evaporation of a mixture of hex- lengths [1.421(2), 1.324(3), and 1.335(2) Å, respectively],

ane with CH₂Cl₂containing equivalent amounts of and by the arrangement of the C(8)C(9)O(3) and N(1)C(7)-

Cu(hfac)₂and 5a. An X-ray study of [Cu(hfac)₂]₃(5a)₂N(2) fragments in almost the same plane (Figure 3). The

showed that 5a performed the function of an O,OЈ bridge latter factor favors the formation of an intramolecular H-

in the trinuclear molecule (Figure 2, a). The Cu(1) atom has bond, O(2)···H(9) [C–H 0.98(2), H···O 2.24(2), C···O

centrosymmetric surroundings in the form of an elongated 2.915(3) Å, angle C–H–O 124.5(13)°]; because of this the

octahedron, in which the O(1s) atom lies in the axial posi- N(2)–O(2) bond length [1.287(2) Å] is slightly greater than

tion [Cu(1)–O(1s) 2.379(4) Å]. The equatorial positions are N(1)–O(1) [1.272(2) Å]. With regard to the crystal structure

occupied by the O_hfacatoms, lying 1.929(4) and 1.937(5) Å of 5b, the paramagnetic molecules form centrosymmetric

away from the Cu(1) atom. The Cu(2) atom is surrounded pairs with O(1)···O(1Ј) distances of 3.514 Å.

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V. Ovcharenko et al.

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Figure 4. ESR spectrum of 5b (bottom trace) and the result of its

modeling (top trace).

Figure 2. a) Independent part of [Cu(hfac)₂]₃(5a)₂and b) polymer

chain in the crystal structure of [Cu(hfac)₂]₃(5a)₂. CF₃groups and

H atoms are omitted for clarity.

for 5b, but not for 5a. The accuracy of hyperfine coupling

constants and g factors is 0.005 mT and 0.0001, respec-

tively.

In general, the two radicals have similar hyperfine pa-

rameters. Their nitrogen hyperfine couplings show that the

two nuclei are not completely equivalent in solution. This

can be explained by the relatively rigid extended π system,

which includes the imidazoline moiety, the ethenyl bridge,

and possibly methoxy/ethoxy oxygen, with the imidazoline

ring having two distinguishable positions relative to the

bridge. Furthermore, the ESR spectra, with a partially re-

solved finer substructure, show clear signs of the alternating

linewidth effect due to the modulation of nitrogen coup-

lings,^[14]most probably because of the bending of the sub-

stituent with respect to the imidazoline ring. A typical spec-

Figure 3. Molecule 5b.

The effects of conjugation between the nitronyl nitroxide trum of this type is shown in Figure 4. It can be seen that

fragment and the substituents, mentioned in the discussion every other line of the dominant quintet (1, 3, 5) has a finer

of the molecular structures of the alkoxyvinyl-substituted substructure, which is lacking in lines 2 and 4.

nitronyl nitroxides 5a and 5b, were also revealed in the ESR

Figure 5 shows the experimentally measured and simu-

spectra of these compounds (see Figure 4 and Supporting lated ESR spectra for 4a·H₂O. The modeling yielded A_N1

Information). The overall spectra are very similar and 0.746 mT, A_N2= 0.738 mT, A_H1= 0.089 mT, A_H2

=

rather typical of 2-imidazoline radicals in that they each 0.228 mT, and g_iso= 2.0066. The fine structure of the lines

contain the dominant quintet from the two nitrogen atoms was not observed, and the spectrum was modeled as a con-

of the imidazoline ring. All spectra show substantial delo- ventional set of 12 protons from the four methyl groups of

calization of spin density to the substituent, which is evi- the imidazoline ring with A_12H= 0.02 mT. The spectra of

dent from the resolved substructures from the two protons 4a·H₂O show closer hyperfine couplings (than those of 5a)

of the ethenyl bridge.

for the two nitrogen atoms, which became nearly equivalent,

The experimentally measured ESR spectra were recorded except that the coupling with one of the bridge protons was

in degassed toluene solutions at concentrations of 10^–5 at increased twofold. Because these spectra lack fine resolu-

room temperature and modeled with Winsim v.0.96.^[13]The tion, no dynamic effects could be observed.

isotropic g factors were determined by use of solid DPPH

In acetal 6a, the oxygen atoms of the paramagnetic frag-

as a standard. Spectrum modeling yielded A_N1= 0.771 mT, ment are not involved in any specific interactions; according

A_N2= 0.747 mT, A_H1= 0.094 mT, A_H2= 0.113 mT, and g_isoto XRD data, the N–O bond lengths are almost equal:

= 2.0064 for 5a and A_N1= 0.775 mT, A_N2= 0.753 mT, A_H11.282(2) and 1.288(2) Å (Figure 6).

= 0.089 mT, A_H2= 0.117 mT, and g_iso= 2.0065 for 5b. Fur-

Radicals 6a and 6b have identical ESR spectra, in which

ther substructure from 12 protons of the four methyl groups each line of the dominant quintet is split into a 1–2–1 triplet

of the imidazoline ring with A_12H= 0.02 mT was resolved from two apparently equivalent methene protons of the

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Nitronyl Nitroxides and Imino Nitroxides

Figure 7. ESR spectrum of 6b (bottom trace) and the result of its

modelling (top trace).

Figure 5. ESR spectrum of 4a·H₂O (bottom trace) and the result

of its modelling (top trace).

by the fact that the intermolecular distances between the O

atoms of N–O groups are large, the minimum distance (for

solid 5b) being 3.514 Å.

MnO₂/Aprotic Solvent (Benzene, DMF, Nitromethane)

Systems

It was interesting to compare the products of the oxi-

dation of 1a in M_xO_y/protic solvent systems with the prod-

ucts of its oxidation in aprotic solvents, for which we chose

benzene, nitromethane, and DMF, with very different po-

larities. Our experiments showed that the oxidation of 1a

with MnO₂, Ni₂O₃, and Co₂O₃(and also PbO₂) in the

Figure 6. Molecule 6a.

bridge, rotating relatively freely with respect to the imid- weakly polar C₆H₆was hindered. After the reaction mix-

azoline moiety (Figure 7 and the Supporting Information). ture had been stirred for 1 day, it had merely become pale

The two side lines of the triplet, which do not exchange as yellow. The same result was observed for the oxidation of

the bridge rotates, have a resolved structure and are due 1a with Ni₂O₃and Co₂O₃(and also PbO₂) in the polar

to the imidazoline methyl groups, whereas the central line solvents MeNO₂and DMF. When the oxidation of 1a with

corresponding to the exchange averaging is not resolved. MnO₂was carried out in MeNO₂or DMF, however, the

These spectra were modeled with use of two nearly equiva- reaction mixture had become blue after 10–15 min because

lent protons of the methylene group. Modeling of the spec- of the formation of 2a in 90% yield (Scheme 4). With re-

tra of both 6a and 6b gave A_N1= A_N2= 0.742 mT, A_H1

=

gard to the nature of the solvent here, it is important to

0.219 mT, A_H2= 0.189 mT, and g_iso= 2.0066. In both cases, emphasize that the oxidation of 1a with MnO₂in polar

12 equiv. protons with A_12H= 0.02 mT were added to ac- aprotic solvents was not accompanied by C–Si bond cleav-

count for the four methyl groups of the imidazoline ring.

age. Consequently, neither M_xO_ynor the reduction prod-

The data for 9a are given in the Supporting Information ucts can have been the bases that induced the splitting of

section because the analogues of these compounds – pyrrol- this bond in the oxidations described in the previous sec-

idin-1-ylvinyl- and diisopropylaminovinyl-substituted ni- tion. For C–Si bond cleavage in 2a, we need a protic sol-

tronyl nitroxides – have been studied previously.^[8]The vent. We did not study the mechanism of bond splitting in

structure of diamagnetic 10 is not discussed here either.

this case, but it obviously did not occur in aprotic solvents.

For 4a·H₂O, 5a, 5b, 6a, and 9a at 40–300 K, the effective This is very important in that it forms a basis for the novel

magnetic moments (µ_eff) are 1.72–1.74 β, in agreement with method of transformation of nitronyl nitroxides into imino

the theoretical value of 1.73 β for noninteracting particles nitroxides, which we found by studying the products of the

with spin S = 1/2 and g = 2 (see the Supporting Infor- reaction of 1a with MnO₂in MeNO₂.

mation). The weak temperature dependence of µ_effindicates

After the reaction mixture had been stirred in DMF for

that the paramagnetic centers are well isolated from one 1 day, the nitronyl nitroxide 2a, formed by the oxidation of

another. This is confirmed by X-ray analysis data, namely 1a with MnO₂, had been slowly deoxygenated, which led to

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2553

V. Ovcharenko et al.

FULL PAPER

would be expected, the only significant difference between

the two radicals is additional proton splitting for 12,

whereas all other parameters of the spectra are very close.

Scheme 4. Reactions of 1a with MnO₂in DMF or MeNO₂.

a decrease in its yield to 73%. If, however, the reaction of

1a was performed with MnO₂in MeNO₂, deoxygenation

was much faster. Compound 2a had been completely trans-

formed into 11a (ca. 80% yield) after 4 h; the TLC plate

did not show any spots for other products. This unexpected

result actually opened up an opportunity for the synthesis

of the previously inaccessible α-ethynyl-substituted imino

nitroxide 12, because methods for splitting the Si–C bonds

in Me₃Si-substituted acetylenes are well developed.^[15]In-

deed, treatment of 11a with a methanol solution of NH₃

caused the transformation of this substrate into the ethynyl-

substituted imino nitroxide 12, isolated in ca. 85% yield

(Scheme 5).

Figure 8. ESR spectrum of 12 (bottom trace) and the result of its

modeling (top trace).

A comparison of the molecular structure of 12 with the

structure of the related 3 shows that the lengths of the triple

C(8)–C(9) [1.182(3) Å] and single C(7)–C(8) [1.433(3) Å]

bonds in 12 are greater (Figure 9, a) than those in 3

[1.106(3) and 1.420(3) Å, respectively].^[9]The motif of the

crystal structure of 12 is similar to that of 3. The structure

of the solid is composed of zigzag chains with weak ϵC–

H···N hydrogen bonds with the parameters C(9)···N(2Ј)

3.364(3), H(9)···N(2Ј) 2.45(3) Å, and angle C(9)H(9)N(2Ј)

168(2)° (Figure 9, b). Although these H-bonds involve the

nitrogen atom of the N=C–N–O^·fragment, the exchange

Scheme 5. Synthesis of the ethynyl-substituted imino nitroxide 12.

Apart from being characterized by C, H, and N micro-

analyses and by high-resolution mass spectroscopy, which

gave satisfactory results, 11a and 12 were also studied by

IR and ESR spectroscopic and magnetochemical measure-

ments, whereas compound 12 was also characterized by X-

ray diffraction. The presence of the terminal acetylene

group in 12 can be inferred from the IR spectrum, which

displays a low-intensity band due to the ν(CϵC) stretching

vibrations at 2120 cm^–1and a strong band due to the ν(ϵC–

H) stretching vibrations at 3192 cm^–1. The free radical char-

acters of 11a and 12 are shown by the effective magnetic

moments (µ_eff), which are almost constant at 40–300 K

(1.78 and 1.73 β, respectively) for these compounds (see the

Supporting Information).

The spectra show a triplet of triplets from two nitrogens

of the imidazoline cycle and are very similar and typical for

small 2-imidazoline-type iminonitroxyl radicals (Figure 8

and the Supporting Information). An additional splitting

from the terminal proton can also be seen as a slight inflec-

tion in the spectra of 12. Modeling of spectra yielded A_N1

= 0.855 mT, A_N2= 0.426 mT, A₁₂= 0.02 mT, and g_iso

2.0060 for 11a and A_N1= 0.867 mT, A_N2= 0.432 mT, A_Ht

= 0.071 mT, A_12H= 0.02 mT, and g_iso= 2.0060 for 12. As Figure 9. a) Molecule and b) crystal packing in 12.

=

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Nitronyl Nitroxides and Imino Nitroxides

interactions between the odd electrons of the paramagnetic Table 2. Preparation of imino nitroxides 11a–m from the corre-

sponding imidazolidine-1,3-diols 1a–m in MnO₂/MeNO₂.

centers of the individual molecules are weak. This is indi-

cated by the fact that µ_effof 12 starts to decrease only at

approximately liquid helium temperature (see the Support-

ing Information).

New Method for the Synthesis of Imino Nitroxides in

MnO₂/MeNO₂

The transformation of 1a into 11a in MnO₂/MeNO₂

stimulated an attempt to extend this method to other ni-

tronyl nitroxides to verify its generality. Indeed, in MnO₂/

MeNO₂, different 1,3-dihydroxyimidazolidines 1 with alkyl,

aryl, or hetaryl groups in their 2-positions gave the corre-

sponding nitronyl nitroxides 2 after 10–20 min, and these

were transformed into imino nitroxides 11 in high yields

(Scheme 6). These results are summarized in Table 2. The

structures of the new nitroxides 11 were supported by satis-

factory C, H, and N microanalyses, by high-resolution mass

spectroscopy, by magnetochemical measurements, and for

well-crystallizable compounds 11 also by X-ray structure

analysis.

Scheme 6.

Two methods for the preparation of imino nitroxides 11

are currently available. The first is the oxidation of a dihy-

droxy derivative 1 into a nitronyl nitroxide 2, which is then

reduced with an appropriate reagent such as NaNO₂,

PPh₃,^[1c]or thiourea.^[16]The second is the oxidation of a

4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole 3-oxide 13,

obtained by thermal^[17]or SeO₂-catalyzed^[18]dehydration of

1. In both procedures, the reactions are performed in se-

quence. A distinction of our method for transforming 1 into

11 in MnO₂/MeNO₂is a transition to a one-pot synthesis

and the use of one reagent: MnO₂. The imino nitroxides

11 obtained in MnO₂/MeNO₂were not contaminated with

diamagnetic nitrones 13, which are always present when

compounds 11 are synthesized by the reduction of 2.

Note that all transformations of 1 into 11 described in

the Experimental Section were carried out at a MnO₂/1 ra-

tio of ca. 15:1 (i.e., with an excess of oxidant). At the mini-

mum required ratio, MnO₂/1m^[19]= 3:1, the oxidant was

completely converted into brownish black MnO(OH), as it

had been in MeOH, but 11m did not form in this case.

Thus, the one-pot synthesis of imino nitroxides 11 required

[a] Yield of the pure isolated product.

that the reaction mixture contained MnO₂. This was also

indicated by the fact that in MeNO₂the addition of a ten-

fold excess of MnO₂to a solution of 2m (or 3) caused its 2m increased to 60 h; in C₆H₆, DMF, MeOH, and EtOH,

transformation into 11m (or 12) within 30 min. When the ca. 40% of the 2m reacted over the same time. In the ab-

amount of MnO₂was decreased to MnO₂/2m = 1:10 in sence of MnO₂(with stirring of a solution of 2m in

MeNO₂, the time required for complete deoxygenation of MeNO₂), no 11m had formed after one day, but TLC

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2555

V. Ovcharenko et al.

FULL PAPER

0.01 mT at 100 kHz, single scan of 4096 points at 1310 ms per

point, time constant 1310 ms, and modeled in free package Winsim

v.0.96 as described earlier.^[13]The magnetochemical experiment was

run on an MPMS-5S (“Quantum Design”) SQUID magnetometer

at temperatures from 2 K to 300 K in a homogeneous external

magnetic field up to 5 kOe. The molar magnetic susceptibility χ

was calculated by Pascal’s additive Scheme including diamagnetic

corrections.

showed the presence of 11m after 60 h. Consequently, deox-

ygenation of nitroxides 2 in solution was considerably ac-

celerated in the presence of MnO₂. Active deoxygenation in

MeNO₂, in which MnO₂also easily oxidized compound 1,

made it possible to perform one-pot conversion of 1 into

11 in MnO₂/MeNO₂.

4,4,5,5-Tetramethyl-2-(pyridin-4-yl)imidazolidine-1,3-diol (1f): Pyr-

idine-4-carboxaldehyde (1.07 g, 10 mmol) was added at room tem-

perature to a stirred suspension of 2,3-bis(hydroxyamino)-2,3-di-

methylbutane (BHA, 1.48 g, 10 mmol) in MeOH (15 mL).^[1]The

reaction mixture was stirred for 3 h and kept at 5 °C for 1 day. The

precipitate was filtered off, washed on the filter with ethyl acetate

and recrystallized from a mixture of MeOH and ethyl acetate. Yield

1.68 g (71%); decomposition temperature 170–175 °C. ¹H NMR

(400 MHz, [D₆]DMSO): δ = 1.00 (s, 6 H, Me), 1.06 (s, 6 H, Me),

4.49 (s, 1 H, 2-H), 7.44 (d, J ≈ 6 Hz, 2 H, 3Ј-H, 5Ј-H), 7.92 (s,

2 H, N–OH), 8.49 (d, J ≈ 6 Hz 2 H, 2Ј-H, 6Ј-H) ppm. ¹³C NMR

(100 MHz, [D₆]DMSO): δ = 150.6 (C), 149.1 (CH), 123.4 (CH),

Conclusions

In this study, cascade reactions have been used for the

synthesis of nitronyl nitroxides. As reaction systems, we

used MnO₂/protic solvent (+ K₂CO₃), in which we per-

formed one-pot transformations of 4,4,5,5-tetramethyl-2-[2-

(trimethylsilyl)ethynyl]imidazolidine-1,3-diol (1a) into the

nitronyl nitroxides (Z)- and (E)-2-(2-methoxyvinyl)-, (E)-2-

[2-(diethylamino)vinyl]-, (E)-2-(2-ethoxyvinyl)-, 2-(2,2-di-

methoxyethyl)- and 2-(2,2-diethoxyethyl)-4,4,5,5-tetrameth-

yl-4,5-dihydro-1H-imidazole-1-oxyl 3-oxide and 4,4,5,5-tet-

ramethyl-2-[2-oxo-1-(4,4,5,5-tetramethylimidazolidin-2-ylid-

ene)ethyl]-4,5-dihydro-1H-imidazole-1-oxyl 3-oxide. We

have found a new method for the transformation of nitronyl

nitroxides and their precursor 2-substituted 4,4,5,5-tetra-

methylimidazolidine-1,3-diols (R = CϵC–SiMe₃, aryl, heta-

ryl, alkyl) into the corresponding imino nitroxides. The high

efficiency of this method with MeNO₂and MnO₂was con-

firmed by the syntheses of a representative series of imino

nitroxides (11a–m). Our data thus suggest that the interac-

tions of M_xO_y(PbO₂, MnO₂, Co₂O₃, Ni₂O₃) with imid-

azolidine-1,3-diols in different solvents can be effectively

used for the synthesis of new polyfunctional nitronyl and

imino nitroxides.

89.1 (CH), 66.5 (C), 24.2 (CH ), 17.2 (CH ) ppm. IR: ν = 2886 (w),

˜

3

2978 (m, CH₃), 3019 (w, C–H_Py), 3186 (br., OH) cm^–1. MS: m/z

(%): 237 [M]⁺(1.0), 202 (7), 148 (10), 147 (100), 123 (17), 105 (11),

98 (10), 84 (12), 69 (11). HRMS calcd. for C₁₂H₁₉N₃O₂[M]⁺

237.1472; found 237.1482. C₁₂H₁₉N₃O₂(237.30): calcd. C 60.7, H

8.1, N 17.7; found C 60.8, H 8.2, N 17.8.

2-(3-Hydroxy-4-nitrophenyl)-4,4,5,5-tetramethylimidazolidine-1,3-

diol (1g): Compound 1g was synthesized from 3-hydroxy-4-ni-

trobenzaldehyde (3.34 g, 0.02 mol) and BHA (2.96 g, 0.02 mol) by

the general procedure for the synthesis of 1f. The product was ob-

tained as a yellow solid (5.40 g, 91%); decomposition temperature

180–190 °C. ¹H NMR (400 MHz, [D₆]DMSO): δ = 1.01 (s, 6 H,

3

Me), 1.04 (s, 6 H, Me), 4.45 (s, 1 H, 2-H), 7.05 (dd, J_5Ј,6Ј= 8.4,

4

⁴J_2Ј,6Ј= 1.5 Hz, 1 H, 6Ј-H), 7.24 (d, J_2Ј,6Ј= 1.5 Hz, 1 H, 2Ј-H),

3

7.83 (d, J_5Ј,6Ј= 8.4 Hz, 1 H, 5Ј-H), 7.88 (s, 2 H, N–OH), 10.8 (s,

1 H, OH) ppm. ¹³C NMR (100 MHz, [D₆]DMSO): δ = 152.3 (C),

150.5 (C), 136.0 (C), 124.9 (CH), 119.8 (CH), 119.0 (CH), 89.8

Experimental Section

(CH), 66.7 (C), 24.6 (CH ), 17.5 (CH ) ppm. IR: ν = 2915 (w),

˜

3

General: Compounds 1a,^[9]1b and 1e,^[20]1c and 1d,^[21]1i,^[22]1j,^[8]

and 1l,^[23]were synthesized by the method reported by Ullman

et al.^[1]Cu(hfac)₂was prepared by the known procedure and puri-

fied by sublimation.^[24]Nickel(III) oxide and cobalt(III) oxide were

synthesized as described in the literature.^[25]Manganese(IV) oxide

(activated, 5 micron, ca. 85%) was purchased from Sigma–Aldrich,

and lead(IV) oxide (97%, A.C.S. reagent) was purchased from Ald-

rich. Other reagents and solvents from commercial sources were of

the highest purity available and were used as received. The reac-

tions were monitored by TLC with “Silica gel 60 F₂₅₄aluminium

sheets, Merck”. Chromatography was carried out with the use of

“Merck” silica gel (0.063–0.100 mm for column chromatography)

for column chromatography. C, H, and N elemental analyses were

carried out by the Chemical Analytical Center of the Novosibirsk

Institute of Organic Chemistry. The melting points were deter-

mined on a Boethius apparatus and not corrected. Infrared spectra

(4000–400 cm^–1) were recorded with a Bruker VECTOR 22 instru-

ment in KBr pellets. ¹H and ¹³C NMR spectra were recorded at

25 °C with a Bruker Avance 400 spectrometer locked to the deute-

rium resonance of the solvent; chemical shifts are reported in parts

per million (ppm) with the solvent as internal standard. HRMS

were recorded on a DFS instrument by the Electron Impact Ioniza-

tion technique (70 eV). X-Band CW ESR spectra were recorded in

dilute degassed toluene solutions at room temperature on a Bruker

EMX spectrometer at MW power 2 mW, modulation amplitude

2990 (m, CH₃), 3238 (br., OH) cm^–1. HRMS calcd. for C₁₃H₁₉N₃O₅

297.1319 [M]⁺; found 297.1318. MS: m/z (%): 297 [M]⁺(0.7), 262

(8), 208 (10), 207 (100), 206 (17), 183 (5), 165 (12), 161 (7), 98 (11),

84 (12), 69 (10). C₁₃H₁₉N₃O₅(297.31): calcd. C 52.5, H 6.4, N 14.1;

found C 52.8, H 6.4, N 14.3.

2-(4-Hydroxy-3-nitrophenyl)-4,4,5,5-tetramethylimidazolidine-1,3-

diol (1h): Compound 1h was synthesized from 4-hydroxy-3-ni-

trobenzaldehyde (3.34 g, 0.02 mol) and BHA (2.96 g, 0.02 mol) by

the general procedure for the synthesis of 1f. The product was ob-

tained as a yellow solid (5.80 g, 98%); decomposition temperature

160–165 °C. ¹H NMR (400 MHz, [D₆]DMSO): δ = 1.01 (s, 6 H,

3

Me), 1.04 (s, 6 H, Me), 4.46 (s, 1 H, 2-H), 7.07 (d, J_5Ј,6Ј= 8.7 Hz,

3

4

1 H, 5Ј-H), 7.57 (dd, J_5Ј,6Ј= 8.7, J_2Ј,6Ј= 2.2 Hz, 1 H, 6Ј-H), 7.81

4

(s, 2 H, N–OH), 7.93 (d, J_2Ј,6Ј= 2.2 Hz, 1 H, 2Ј-H), 10.8 (s, 1 H,

OH) ppm. ¹³C NMR (100 MHz, [D₆]DMSO): δ = 151.9 (C), 136.4

(C), 135.9 (CH), 133.7 (C), 124.7 (CH), 118.7 (CH), 89.1 (CH),

66.5 (C), 24.6 (CH ), 17.6 (CH ) ppm. IR: ν = 2916 (w), 2991 (m,

˜

3

CH₃), 3060 (w, C–H_Ar), 3229 (br., OH) cm^–1. MS: m/z (%): 297

[M]⁺(0.4), 208 (11), 207 (100), 206 (10), 182 (5), 165 (7), 161 (8),

98 (8), 84 (11), 69 (11). HRMS calcd. for C₁₃H₁₉N₃O₅[M]⁺

297.1319; found 297.1322. C₁₃H₁₉N₃O₅(297.31): calcd. C 52.5, H

6.4, N 14.1; found C 52.4, H 6.6, N 14.1.

2,4,4,5,5-Pentamethylimidazolidine-1,3-diol (1k): CH₃CHO (6 mL)

was added to a suspension of BHA·H₂SO₄·H₂O (20.0 g, 0.076 mol)

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Nitronyl Nitroxides and Imino Nitroxides

in water (30 mL), and the reaction mixture was stirred for 2 h. A

solution of NaOH (5.4 g, 0.135 mol) in water (10 mL) was added

dropwise to the solution; then Na₂CO₃(2.0 g, 0.019 mol) was

added in portions (because of strong foaming). The resulting prod-

uct 1k was filtered off, dried in vacuo, and recrystallized from

spectrum recording conditions, 4a·H₂O was dehydrated, and prod-

uct 4a isomerized into 5a.) HRMS calcd. for C₁₀H₁₇N₂O₃[M]⁺

213.1239; found 213.1231. C₁₀H₁₉N₂O₄(231.27): calcd. C 51.9, H

8.3, N 12.1; found C 52.0, H 8.0, N 12.3.

Product 5a: Yield 90 mg (22%); blue finely crystalline powder; m.p.

84–86 °C; at room temperature, 5a in MeOH in the presence of

K₂CO₃quantitatively transformed into 6a. µ_eff= 1.73 B.M. (5–

300 K). MS: m/z (%): 214 [M + 1]⁺(9.5), 213 (100) [M]⁺, 151 (5),

114 (8), 85 (18), 84 (95), 69 (71), 56 (18). HRMS calcd. for

C₁₀H₁₇N₂O₃[M]⁺213.1239; found 213.1225. C₁₀H₁₇N₂O₃(213.26):

calcd. C 56.3, H 8.0, N 13.1; found C 56.3, H 8.1, N 13.1.

1

MeOH. Yield 7.2 g (71%); m.p. 149–150 °C. H NMR (400 MHz,

[D₆]DMSO): δ = 0.96 (s, 12 H, Me), 1.13 (d, ³J₂= 5.9 Hz, 3 H,

3

Me), 3.70 (q, J_Me= 5.9 Hz, 1 H, 2-H), 7.58 (s, 2 H, N–OH) ppm.

¹³C NMR (100 MHz, [D₆]DMSO): δ = 82.7, 65.5, 22.9, 18.8,

18.0 ppm. IR: ν = 2915 (w), 2977 (m, CH ), 3252 (br., OH) cm^–1.

˜

3

MS: m/z (%): 174 [M]⁺(1.8), 101 (14), 100 (11), 98 (18), 84 (100), 69

(8). HRMS calcd. for C₈H₁₈N₂O₂[M]⁺174.1363; found 174.1364.

C₈H₁₈N₂O₂(174.24): calcd. C 55.2, H 10.4, N 16.1; found C 54.9,

H 10.4, N 16.0.

Product 6a: Yield 20 mg (4%).

Other experiments on the oxidation of 1a with M_xO_yin ROH

(Table 1) were carried out by similar procedures; compounds 2a,^[9]

5b, 6a, 6b, and 7^[11]were identified by comparing their IR spectra,

R_fvalues, and spot colors (TLC) with those of authentic samples.

2-(3-Bromophenyl)-4,4,5,5-tetramethylimidazolidine-1,3-diol (1m):

Compound 1m was synthesized from 3-bromobenzaldehyde

(1.85 g, 10 mmol) and BHA (1.48 g, 10 mmol) by the general pro-

cedure for the synthesis of 1f; the product was obtained as a pale

yellow solid (1.90 g, 71%); m.p. 194–196 °C (from ethyl acetate).

¹H NMR (400 MHz, [D₆]DMSO): δ = 1.00 (s, 6 H, Me), 1.04 (s,

2-(2,2-Dimethoxyethyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-

1-oxyl 3-Oxide (6a): MnO₂(1.02 g, 11.7 mmol) was added at room

temperature to a solution of 1a (200 mg, 0.78 mmol) in MeOH

(10 mL). The reaction mixture was stirred for 20 min and filtered.

K₂CO₃(100 mg) was added to the filtrate containing 3. The mix-

ture was stirred for 24 h (until 5a had vanished) and was then fil-

tered, and the solvents were evaporated. The residue was chromato-

graphed on a silica gel column to give 6a. Yield 105 mg (55%);

claret red crystals; m.p. 69–70 °C. UV/Vis (EtOH): λ_max(ε,

3

6 H, Me), 4.47 (s, 1 H, 2-H), 7.26 (distorted t, J_4Ј,6Ј≈ 8 Hz, 1 H),

4

7.45 (m, 2 H), 7.66 (distorted t, J_4Ј,6Ј≈ 2 Hz, 1 H, 2Ј-H), 7.84 (s,

2 H, N–OH) ppm. ¹³C NMR (100 MHz, [D₆]DMSO): δ = 144.9

(C), 130.8 (CH), 130.1 (CH), 129.8 (CH), 127.6 (CH), 121.2 (C),

89.5 (CH), 66.3 (C), 24.4 (CH ), 17.2 (CH ) ppm. IR: ν = 2914 (w),

˜

3

2992 (m, CH₃), 3224 (br., OH) cm^–1. MS: m/z (%): 316 [M + 2]⁺

(0.9), 314 [M]⁺(0.9), 227 (13), 226 (99), 225 (14), 224 (100), 202

(7), 200 (7), 100 (8), 98 (15), 89 (6), 84 (10), 69 (9). HRMS calcd.

for C₁₃H₁₉BrN₂O₂[M]⁺314.0624; found 314.0621. C₁₃H₁₉BrN₂O₂

(315.21): calcd. C 49.5, H 6.1, Br 25.4, N 8.9; found C 49.3, H 5.9,

Br 25.1, N 8.9.



^–1cm^–1) = 216 (10000), 263 (8800), 339 sh. (6200), 353 (11000),

607 (380), 655 (290) nm. µ_eff= 1.74 B.M. (75–300 K). MS: m/z

(%):245 [M]⁺(6.8), 214 (6), 84 (25), 75 (100), 69 (14). HRMS calcd.

for C₁₁H₂₁N₂O₄[M]⁺245.1496; found 245.1496. C₁₁H₂₁N₂O₄

(245.30): calcd. C 53.9, H 8.6, N 11.4; found C 53.7, H 8.9, N 11.4.

General Procedure for the Oxidation of 1a in M_xO_y/ROH Systems

{with MnO₂/MeOH as an example (Entry 9, Table 1)}

(E)-2-(2-Ethoxyvinyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-

1-oxyl 3-Oxide (5b): MnO₂(1.02 g, 11.7 mmol) was added to a

solution of 1a (200 mg, 0.78 mmol) in EtOH (10 mL). The mixture

was stirred at room temperature for 20 min and filtered. K₂CO₃

(100 mg) was then added to the solution of 3. The mixture was

stirred for 50 h (until compound 3 had vanished) and filtered, and

the solvents were evaporated. The residue was kept in vacuo for

24 h and then dissolved in hexane. The resulting solution was

heated with boiling for 3 h and concentrated {according to TLC

data, in the course of this procedure, the blue-violet compound

with R_f= 0.19 (AcOEt), presumably (Z)-2-(2-ethoxyvinyl)-4,4,5,5-

tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl 3-oxide hydrate

(4b·H₂O), mostly transformed into 5b (R_f= 0.60, AcOEt)}. The

resulting mixture was separated on a column {35ϫ1.5 cm; eluents

EtOAc for 5b and a mixture of EtOAc and MeOH (5:1, v/v) for

4b·H₂O}; product 5b was isolated. Yield 75 mg (42%); blue crys-

Characterization of (Z)-2-(2-Methoxyvinyl)-4,4,5,5-tetramethyl-4,5-

dihydro-1H-imidazole-1-oxyl 3-Oxide Hydrate (4a·H₂O) and (E)-2-

(2-Methoxyvinyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-

Oxyl 3-Oxide (5a): MnO₂(2.5 g, 28.8 mmol) was added to a solu-

tion of 1a (500 mg, 1.95 mmol) in MeOH (25 mL). The resulting

reaction mixture was stirred at room temperature for 20 h and then

filtered, and the solvents were evaporated. The residue was chro-

matographed on a column (25ϫ1.5 cm, ethyl acetate as an eluent).

A blue [compound 5a with R_f= 0.52 (AcOEt)] and a crimson [com-

pound 6a, R_f= 0.40 (AcOEt)] fraction were collected. The column

was then eluted with a mixture of ethyl acetate and MeOH

(5:1, v/v), and a blue-violet fraction was collected [compound

4a·H₂O with R_f= 0.14 (AcOEt)]. The fractions were concentrated

and again chromatographed. The products 4a·H₂O, 5a, and 6a were

dissolved in hexane at 40–50 °C, and the solutions were filtered

and cooled. The crystalline precipitate 4a·H₂O was filtered off and

washed on a filter with cold hexane. Nitroxide 5a was initially iso-

lated as a dense oil, which crystallized on grinding with cold hex-

ane. The first portions of 6a were isolated as a dense oil; the mother

solution was then decanted and stored at –15 °C for 24 h, which

gave 6a in the form of intergrown crystals.

tals; m.p. 66–68 °C. IR: ν = 2936 (w), 2978 (m, CH), 3056 (w,

˜

=C–H) cm^–1. UV/Vis (CHCl₃): λ_max(ε, ^–1cm^–1) = 272 (11891),

266 (9572), 626 (1216), 630 sh. (1206), 683 sh. (1172) nm. µ_eff

=

1.73 B.M. (75–300 K). MS: m/z (%): 228 [M + 1]⁺(11.7), 227

[M]⁺(79), 114 (13), 99 (9), 98 (8), 84 (100), 83 (18), 71 (12). HRMS

calcd. for C_{1 1}H_{1 9}N₂O₃[M]⁺227.1390; found 227.1392.

C₁₁H₁₉N₂O₃(227.28): calcd. C 58.1, H 8.4, N 12.3; found C 58.3,

H 8.5, N 12.3.

Product 4a·H₂O: Yield 210 mg (46%); blue-violet needle crystals;

m.p. 48–50 °C. The mass of 4a·H₂O had not changed after the

product had been kept in vacuo (Ͻ 1 Torr) at room temperature

for 24 h. According to TLC data, on boiling in C₆H₆, 4a·H₂O gave

2-(2,2-Diethoxyethyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-

1-oxyl 3-Oxide (6b)

Procedure 1: K₂CO₃(40 mg) was added to a solution of 5b (40 mg,

0.18 mmol) in EtOH (10 mL). The mixture was stirred while boil-

ing for 7 h (until 5b had vanished) and was then filtered, and the

a number of products, including 5a. IR: ν = 2939 (w), 2991 (m,

˜

CH₃), 3455 (br), 3511 (br., OH) cm^–1. µ_eff= 1.74 B.M. (5–300 K).

MS: m/z (%): 214 [M + 1]⁺(4.8), 213 [M]⁺(38.8), 151 (4), 114 (7), solvents were evaporated. The residue was purified by column

85 (12), 84 (100), 83 (9), 70 (4), 69 (92), 56 (18). (Under the mass

chromatography (30ϫ1.5 cm, EtOAc as eluent). A claret red frac-

Eur. J. Org. Chem. 2009, 2548–2561

www.eurjoc.org

2557

V. Ovcharenko et al.

FULL PAPER

tion with R_f= 0.40 AcOEt was collected and evaporated to give

6b. Yield 25 mg (52 %); claret red oil. UV/Vis (EtOH): λ_max(ε,

0.027 mT (for details see the Supporting Information). MS: m/z

(%): 255 [M + 1]⁺(16.9), 254 (100) [M]⁺, 237 (15), 222 (10), 220

(12), 178 (12), 126 (73), 125 (35), 124 (67), 123 (23), 109 (32), 84



^–1cm^–1) = 215 (10000), 260 (8800), 340 sh. (6100), 350 (11000),

610 (370), 650 (300) nm. MS: m/z (%): 273 [M]⁺(7.30), 228 (18), (34). HRMS calcd. for C₁₃H₂₄N₃O₂[M]⁺254.1863; found

195 (6), 156 (10), 114 (6), 103 (100), 98 (7), 84 (53). HRMS calcd. 254.1861. C₁₃H₂₄N₃O₂(254.35): calcd. C 61.4, H 9.5, N 16.5; found

for C₁₃H₂₅N₂O₄[M]⁺273.1809; found 273.1821. C₁₃H₂₅N₂O₄C 61.1, H 9.8, N 16.4.

(273.35): calcd. C 57.1, H 9.2, N 10.3; found C 57.5, H 9.3, N 10.7.

N-(2,3-Dimethyl-3-nitrobutan-2-yl)formamide (10): MnO₂(260 mg,

Procedure 2: A mixture prepared by the addition of MnO₂(1.02 g,

3.0 mmol) was added at room temperature to a solution of 1a

(50 mg, 0.20 mmol) in Bu^tNH₂(3 mL). The reaction mixture was

stirred for 24 h and then filtered, and the solvents were evaporated.

The residue was filtered through a silica gel layer (1.5ϫ15 cm, Ac-

OEt), the solution was concentrated, and the residue was recrys-

tallized from hexane to give 10. Yield 26 mg (74%); colorless crys-

11.7 mmol) to a solution of 1a (200 mg, 0.78 mmol) in EtOH

(10 mL) was stirred at room temperature for 20 min and filtered.

KOH (100 mg) was added to the resulting solution of 3. The mix-

ture was stirred at room temperature for 10 h (until 3 had vanished)

and was then filtered, and the solvents were evaporated. The resi-

due was ground with ethyl acetate (ca. 10 mL) and the solution was

decanted; the process was repeated until the next portion of ethyl

acetate ceased to be colored. The consolidated solutions were evap-

orated, and the residue was chromatographed to give 6b with a

yield of 70 mg (33%).

1

tals; m.p. 189–190 °C. H NMR (400 MHz, CDCl₃) (1:1.3 mixture

of formamide rotamers, signals from major rotamer marked with

an asterisk *): δ = 1.38* (s, 12 H, Me), 1.48 (s, 12 H, Me), 1.60* (s,

12 H, Me), 1.64 (s, 12 H, Me), 6.1 (brs, 1 H, NH), 7.0* (brd, J

≈ 11 Hz, 1 H, NH), 8.11 (d, J = 2.0 Hz, 1 H, CHO), 8.11* (d, J =

11.4 Hz, 1 H, CHO) ppm. ¹³C NMR (100 MHz, [D₆]DMSO) (1:1.3

mixture of formamide rotamers): δ = 164.7, 162.6, 96.6, 95.9, 60.6,

[Cu(hfac)₂]₃(5a)₂Complex: Cu(hfac)₂(11 mg, 0.023 mmol) was

added to a solution of 5a (5.1 mg, 0.024 mmol) in a mixture of

CH₂Cl₂(1 mL) and n-heptane (3 mL). The resulting solution was

kept in an open flask at 5 °C. After the mother solution was almost

completely decolorized, the crystals were filtered off and dissolved

in n-heptane (5 mL) at 50–55 °C. The solution was filtered, and the

filtrate was kept at –15 °C for 1 d. The resulting greenish-brown

dichroic crystals were filtered off, washed with cold hexane on a

filter (1 mL), and dried in air. Yield 8.4 mg (38% based on 5a). IR:

59.0, 26.1, 24.8, 24.3, 24.2 ppm. IR: ν = 1308 (s), 1530 (s, NO ),

˜

2

1695 (s, C=O), 2932 (m), 2998 (m, CH₃), 3105 (s), 3211 (s,

NH) cm^–1. MS: m/z (%): 128 [M – NO₂]⁺(2.5), 113 (7), 86 (100),

85 (5), 84 (7), 83 (39), 58 (61). HRMS calcd. for C₇H₁₄NO [M –

NO₂]⁺fragment ion 128.1070; found 128.1068. C₇H₁₄N₂O₃

(174.20): calcd. C 48.3, H 8.1, N 16.1; found C 48.2, H 8.4, N 16.3.

General Procedure for the Preparation of Imino Nitroxides 11. Ex-

ample: 4,4,5,5-Tetramethyl-2-[2-(trimethylsilyl)ethynyl]-4,5-dihydro-

1H-imidazole-1-oxyl (11a): MnO₂(1.0 g, 11.5 mmol) was added at

room temperature to a stirred solution of 1 (200 mg, 0.78 mmol) in

MeNO₂(12 mL). The reaction mixture was stirred for 4 h and fil-

tered. The solution was diluted with n-heptane (12 mL) and con-

centrated to a volume of ca. 2 mL on a rotary evaporator with

bath temperature 30–35 °C. The solution was placed on a column

(10ϫ1.5 cm, wetted with CHCl₃). The column was eluted with

CHCl₃, and an orange fraction was collected and then evaporated.

The residue was dissolved in a minimum amount of hexane (ca.

5 mL) at room temperature, and the solution was filtered and kept

at –10 °C for 10 h. The deposited orange-colored flakes were

rapidly filtered out and washed with cold hexane. The yield of the

crystalline 11a was 80 mg (43%). The mother solution was further

evaporated, which produced an additional 70 mg of 11a (total yield

81%) in the form of an amorphous powder with spectral and ana-

lytical data identical to those of the crystalline sample; m.p. 73–

75 °C (hexane); R_f= 0.63 (CH₂Cl₂). µ_eff= 1.73 B.M. (50–300 K).

MS: m/z (%): 237 [M]⁺(1.0), 165 (6), 114 (8), 97 (6), 85 (6), 84

(100), 69 (28). HRMS calcd. for C₁₂H₂₁N₂OSi [M]⁺237.1418;

found 237.1417. C₁₂H₂₁N₂OSi (237.40): calcd. C 60.7, H 8.9, N

11.8; found C 60.8, H 8.8, N 11.8.

ν = 545, 596, 617, 680, 746, 801, 846, 864, 962, 989, 1150, 1207,

˜

1262, 1337, 1400, 1482, 1531, 1558, 1644 cm^–1(the other absorp-

tion bands have an intensity of less than 5% of the intensity of the

1150 cm^–1band). µ_eff≈ 2.00 B.M. (10–200 K). C₅₀H₄₀Cu₃F₃₆N₄O₁₈

(1859.45): calcd. C 32.3, H 2.2, N 3.0; found C 32.4, H 2.3, N 3.3.

4,4,5,5-Tetramethyl-2-[2-oxo-1-(4,4,5,5-tetramethylimidazolidin-2-yl-

idine)ethyl]-4,5-dihydro-1H-imidazole-1-oxyl 3-Oxide (7): MnO₂

(204 mg, 2.35 mmol) was added at room temperature to a solution

of 1a (200 mg, 0.78 mmol) in EtOH (5 mL). The reaction mixture

was stirred for 60 h and filtered. Toluene (5 mL) was added to the

filtrate, and the solution was concentrated in vacuo to a volume of

ca. 2 mL and placed on a silica gel column (1.5ϫ20 cm). The col-

umn was eluted with ethyl acetate, and a blue fraction of nitroxide

7 with R_f= 0.31 AcOEt was collected. The fraction was concen-

trated, the residue was dissolved in ether, and the resulting solution

was filtered. The filtrate was diluted with n-heptane (a volume one

third of the volume of the filtrate) and evaporated to give 7 (43 mg,

34%). The spectroscopic data and melting point of nitroxide 7 are

identical to those obtained earlier.^[11]

(E)-2-[2-(Diethylamino)vinyl]-4,4,5,5-tetramethyl-4,5-dihydro-1H-

imidazole-1-oxyl 3-Oxide (9a): MnO₂(260 mg, 3.0 mmol) was

added at room temperature to a solution of 1a (50 mg, 0.20 mmol)

in Et₂NH (5 mL). The reaction mixture was stirred for 40 min and

filtered, and the solvents were evaporated. The residue was chro-

matographed on a silica gel column (1.5ϫ20 cm); the side products

were eluted with ethyl acetate. The column was then eluted with a

mixture of ethyl acetate with MeOH (5:1, v/v), and a turquoise-

colored fraction with R_f= 0.44 AcOEt was collected. The solution

was concentrated, and the residue was recrystallized from hexane

to give 9a. Yield 15 mg (30 %); dark green needles; m.p. 105–

106 °C. UV/Vis (CHCl₃): λ_max(ε, ^–1cm^–1) = 313 (31043), 389 sh.

4,4,5,5-Tetramethyl-2-(1-methyl-1H-pyrazole-4-yl)-4,5-dihydro-1H-

imidazole-1-oxyl (11b): Compound 11b was obtained as red-orange

crystals (90 mg, 89%) from 1b (110 mg, 0.46 mmol) by the general

procedure; R_f= 0.33 (EtOAc). MS: m/z (%): 221 [M]⁺(2.5), 149

(7), 114 (18), 108 (18), 85 (6), 84 (100), 69 (43). HRMS calcd. for

C₁₁H₁₇N₄O [M]⁺221.1397; found 221.1399. The melting point and

spectroscopic data were identical with those reported in the litera-

ture.^[22]

(3840), 748 (2617) nm. µ_eff= 1.73 B.M. (75–300 K). ESR: g_iso

2.0064; A_N1(1N) = 0.822 mT, A_N2(1N) = 0.750 mT A_(CH3)(12H) =

=

4,4,5,5-Tetramethyl-2-(1,3-dimethyl-1H-pyrazole-4-yl)-4,5-dihydro-

1H-imidazole-1-oxyl (11c):^[22]Compound 11c was obtained as red-

0.025 mT, A_Hsub(1H) = 0.095 mT, A_Hsub(1H) = 0.033 mT, orange crystals (50 mg, 90%) from 1c (60 mg, 0.24 mmol) by the

A_Nsub(1N) = 0.036 mT, A_(CH2)(4H) = 0.044 mT, A_{(CH CH )}(6H) = general procedure; R_f= 0.58 (EtOAc). MS: m/z (%): 235 [M]⁺(2.6),

2

3

2558

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Eur. J. Org. Chem. 2009, 2548–2561

Nitronyl Nitroxides and Imino Nitroxides

122 (17), 114 (17), 85 (5), 84 (100), 69 (42). HRMS calcd. for

C₁₂H₁₉N₄O [M]⁺235.1553; found 235.1559.

= 0.018 mT. HRMS calcd. for C₈H₁₅N₂O [M]⁺155.1179; found

155.1182.

4,4,5,5-Tetramethyl-2-(1,5-dimethyl-1H-pyrazole-4-yl)-4,5-dihydro-

1H-imidazole-1-oxyl (11d):^[22]Compound 11d was obtained as red-

orange crystals (26 mg, 94%) from 1d (30 mg, 0.12 mmol) by the

general procedure. MS: m/z (%): 235 [M]⁺(1.4), 122 (16), 121 (100),

120 (86), 114 (10), 93 (8), 84 (53), 69 (21). HRMS calcd. for

C₁₂H₁₉N₄O [M]⁺235.1553; found 235.1560.

4,4,5,5-Tetramethyl-2-[4-(6-methylpyridin-3-ylethynyl)phenyl]-4,5-di-

hydro-1H-imidazole-1-oxyl (11l):^[23]Compound 11l was obtained as

red-orange crystals (210 mg, 93%) from 1l (240 mg, 0.68 mmol) by

the general procedure; R_f= 0.68 (EtOAc). MS: m/z (%): 332 [M]⁺

(1.4), 316 (8), 260 (23), 248 (20), 219 (54), 218 (63), 191 (6), 190

(25), 151 (8), 114 (23), 85 (7), 84 (100), 69 (41). HRMS calcd. for

C₂₁H₂₂N₃O [M]⁺332.1757; found 332.1755.

2-(1-Ethyl-1H-pyrazole-4-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-

imidazole-1-oxyl (11e):^[22]Compound 11e was obtained as red-

orange crystals (31 mg, 84%) from 1e (40 mg, 0.16 mmol) by the

general procedure; R_f= 0.48 (EtOAc). MS: m/z (%): 235 [M]⁺(1.1),

163 (6), 122 (15), 114 (15), 85 (6), 84 (100), 69 (44). HRMS calcd.

for C₁₂H₁₉N₄O [M]⁺235.1553; found 235.1556.

2-(3-Bromophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-

oxyl (11m): Compound 11m was obtained as red crystals (257 mg,

87%) from 1m (315 mg, 1 mmol) by the general procedure; m.p.

58–59 °C (hexane); R_f= 0.88 (EtOAc). µ_eff= 1.73 B.M. (30–300 K).

MS: m/z (%): 297 [M + 2]⁺(0.56), 295 [M]⁺(0.51), 225 (6), 223 (6),

184 (8), 183 (8), 114 (16), 85 (6), 84 (100), 69 (41). HRMS calcd.

for C₁₃H₁₆BrN₂O [M]⁺295.0441; found 295.0445. C₁₃H₁₆BrN₂O

(296.18): calcd. C 52.7, H 5.4, Br 27.0, N 9.5; found C 52.4, H 5.3,

Br 27.4, N 9.7.

4,4,5,5-Tetramethyl-2-(pyridin-4-yl)-4,5-dihydro-1H-imidazole-1-

oxyl (11f): Compound 11f was obtained as red-orange crystals

(180 mg, 65%) from 1f (300 mg, 1.26 mmol) by the general pro-

cedure; m.p. 72–73 °C (hexane); R_f= 0.46 (EtOAc). µ_eff

=

1.73 B.M. (75–300 K). MS: m/z (%): 218 [M]⁺(2.4), 146 (11), 114

(14), 105 (18), 84 (100), 69 (53). HRMS calcd. for C₁₂H₁₆N₃O

[M]⁺218.1293; found 218.1293. C₁₂H₁₆N₃O (218.28): calcd. C 66.0,

H 7.4, N 19.3; found C 65.6, H 7.3, N 19.3.

2-Ethynyl-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl (12):

Nitroxide 11a (50 mg, 0.21 mmol) was dissolved in a solution of

NH₃in MeOH (14%, 3 mL), and the resulting solution was stirred

at room temperature. A TLC analysis of the reaction mixture indi-

cated that after 60 min the orange spot with R_f= 0.63 (CH₂Cl₂)

had vanished completely, while an orange spot with R_f= 0.26

(CH₂Cl₂) had formed. The solution was diluted with benzene

(3 mL) and concentrated to a volume of about 1 mL on a rotary

evaporator at 30–35 °C (bath temperature). The solution was

placed on a column (8ϫ1.5 cm, wetted with CH₂Cl₂). The column

was eluted with CH₂Cl₂, and an orange fraction was collected and

concentrated. The residue was dissolved in CH₂Cl₂(3 mL), n-hep-

tane (3 mL) was added to the solution, and the solution was kept

in an open flask at ca. 5 °C to give orange needle-shaped crystals

suitable for X-ray analysis. Yield 30 mg (86%); m.p. 58–60 °C, R_f

2-(3-Hydroxy-4-nitrophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-

imidazole-1-oxyl (11g): Compound 11g was obtained as orange

crystals (105 mg, 75%) from 1g (150 mg, 0.50 mmol) by the general

procedure; m.p. 111.5–112.5 °C (hexane); R = 0.89 (EtOAc). IR: ν

˜

f

= 2982 (m, CH₃), 3243 (br), 3454 (br., OH) cm^–1. µ_eff= 1.73 B.M.

(40–300 K). MS: m/z (%): 278 [M]⁺(0.8), 206 (16), 165 (13), 114

(14), 84 (100), 69 (47). HRMS calcd. for C₁₃H₁₆N₃O₄[M]⁺

278.1135; found 278.1134. C₁₃H₁₆N₃O₄·0.5H₂O (287.30): calcd. C

54.4, H 6.0, N 14.7; found C 54.6, H 6.1, N 15.0.

2-(4-Hydroxy-3-nitrophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-

imidazole-1-oxyl (11h): Compound 11h was obtained as orange

crystals (75 mg, 66%) from 1h (120 mg, 0.40 mmol) by the general

= 0.26 (CH Cl ). IR: ν = 2120 (s, CϵC), 2869 (w), 2977 (m, CH ),

˜

2

3

3192 (s, ϵC–H) cm^–1. µ_eff= 1.73 B.M. (30–300 K). MS: m/z (%):

165 [M]⁺(5), 149 (7), 114 (11), 93 (22), 92 (14), 84 (100), 69 (83).

HRMS calcd. for C₉H₁₃N₂O [M]⁺165.1022; found 165.1023.

C₉H₁₃N₂O (165.22): calcd. C 65.4, H 7.9, N 17.0; found C 65.4, H

8.0, N 17.0.

procedure; m.p. 121–123 °C (hexane); R = 0.87 (EtOAc). IR: ν =

˜

f

2930 (w), 2979 (m, CH₃), 3103 (w, C–H_Ar), 3247 (br., OH) cm^–1.

µ_eff= 1.73 B.M. (50–300 K). MS: m/z (%): 278 [M]⁺(0.74), 206

(23), 165 (16), 114 (14), 85 (7), 84 (100), 69 (45). HRMS calcd. for

C₁₃H₁₆N₃O₄[M]⁺278.1135; found 278.1134. C₁₃H₁₆N₃O₄(278.29):

calcd. C 56.1, H 5.8, N 15.1; found C 56.3, H 5.7, N 14.9.

X-ray Structure Determinations: Crystal data for compounds were

collected on a Smart APEX CCD diffractometer with use of graph-

ite-monochromated Mo-K_α(λ = 0.71073 Å). In all cases, data were

collected in a hemisphere of reciprocal space with use of a combi-

nation of five exposure sets. The cell parameters were determined

and refined by the least-squares method for all reflections. The first

50 frames were collected again in order to monitor crystal decay at

the end of data collection, and no appreciable decay was observed.

The structures were solved by direct methods and refined by least-

squares procedures on F². All non-hydrogen atoms were refined

anisotropically. Some of the hydrogen atoms were localized in ∆ρ

syntheses and refined isotropically; the others were calculated geo-

metrically and refined as riding on the corresponding carbon-

bonded atoms. All structure solution and refinement calculations

were performed with Bruker Shelxtl Version 6.12.

4,4,5,5-Tetramethyl-2-(1-methyl-1H-pyrazole-5-yl)-4,5-dihydro-1H-

imidazole-1-oxyl (11i):^[22]Compound 11i was obtained as red-

orange crystals (43 mg, 85%) from 1i (55 mg, 0.23 mmol) by the

general procedure; R_f= 0.77 (EtOAc). MS: m/z (%): 221 [M]⁺(2),

205 (8), 149 (14), 148 (10), 114 (21), 108 (18), 84 (100), 69 (22).

HRMS calcd. for C₁₁H₁₇N₄O [M]⁺221.1397; found 221.1399.

4,4,5,5-Tetramethyl-2-{4-[(trimethylsilyl)ethynyl]phenyl}-4,5-dihy-

dro-1H-imidazole-1-oxyl (11j): Compound 11j was obtained as red-

orange crystals (66 mg, 88%) from 1j (80 mg, 0.24 mmol) by the

general procedure; m.p. 170–171.5 °C (hexane); R_f= 0.91 (EtOAc).

IR: ν = 2158 (w, CϵC), 2971 (m, CH ) cm^–1. µ_eff= 1.73 B.M. (30–

˜

3

300 K). MS: m/z (%): 313 [M]⁺(0.6), 241 (11), 200 (8), 184 (17),

114 (14), 85 (5), 84 (100), 69 (22). HRMS calcd. for C₁₈H₂₅N₂OSi

[M]⁺313.1731; found 313.1740. C₁₈H₂₅N₂OSi (313.49): calcd. C

69.0, H 8.0, N 9.0; found C 69.2, H 8.1, N 9.0.

Compound 4a·H₂O: The crystals were grown from hexane at ca.

5 °C. Crystal data and details of experiment are T = 240 K, a =

2,4,4,5,5-Pentamethyl-4,5-dihydro-1H-imidazole-1-oxyl (11k):^[1c]8.217(9), b = 7.205(8), c = 10.667(11) Å, β = 101.82(2)°, V =

Compound 11k was obtained as a peach-colored oil (main compo-

nent in LC-MSD, 180 mg, 40%) from 1k (0.5 g, 2.9 mmol) by the

general procedure; R_f= 0.49 (EtOAc). ESR: g_iso= 2.0059; A_N1(1N)

618.1(11) Å³, P2₁, Z = 2, D_C= 1.243 gcm^–3, µ = 0.096 mm^–1, 1.95

Ͻ θ Ͻ 26.50°, I_hkl(coll/uniq) 6050/2513, R_int= 0.0665, Goof =

1.091, R1 = 0.0778, wR2 = 0.1657 (I Ͼ 2σ_I), R1 = 0.1070, wR2 =

= 0.917 mT, A_N2(1N) = 0.404 mT, A_Me(3H) = 0.182 mT, A_Me(12H) 0.1781 (all data).

Eur. J. Org. Chem. 2009, 2548–2561

www.eurjoc.org

2559

V. Ovcharenko et al.

FULL PAPER

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Compound [Cu(Hfac)₂]₃(5a)₂: The crystals were grown by slow

evaporation of a solution of the complex in a mixture of CH₂Cl₂

with n-heptane. Crystal data and details of experiment are T =

240 K, a = 10.738(3), b = 12.005(3), c = 15.630(4) Å, α =

3

¯

71.096(4)°, β = 82.012(4)°, γ = 69.588(4)°, V = 1785.7(8) Å , P1, Z

= 2, D_C= 1.729 gcm^–3, µ = 1.045 mm^–1, 1.90 Ͻ θ Ͻ 26.46°, I_hkl

(coll/uniq) 18063/7285, R_int= 0.0761, Goof = 0.884, R1 = 0.0495,

wR2 = 0.0961 (I Ͼ 2σ_I), R1 = 0.0787, wR2 = 0.1058 (all data).

Compound 5b: The crystals were grown from hexane at –15 °C.

Crystal data and details of experiment are T = 150 K, a =

6.2041(12), b = 12.195(2), c = 16.467(3) Å, β = 97.65(1)°, V =

1234.7(4) Å³, P2₁/n, Z = 4, D_C= 1.223 gcm^–3, µ = 0.089 mm^–1,

2.08 Ͻ θ Ͻ 29.65°, I_hkl(coll/uniq) 14153/3248, R_int= 0.1312, Goof

= 0.816, R1 = 0.0539, wR2 = 0.1186 (I Ͼ 2σ_I), R1 = 0.1200, wR2

= 0.1342 (all data).

[3]

Compound 6a: The crystals were grown from hexane at –15 °C.

Crystal data and details of experiment are T = 240 K, a =

7.7576(16), b = 9.975(2), c = 17.270(4) Å, V = 1336.4(5) Å³,

P2₁2₁2₁, Z = 4, D_C= 1.219 gcm^–3, µ = 0.092 mm^–1, 2.36 Ͻ θ Ͻ

29.47°, I_hkl(coll/uniq) 14411/3364, R_int= 0.0589, Goof = 1.044, R1

= 0.0517, wR2 = 0.1256 (I Ͼ 2σ_I), R1 = 0.596, wR2 = 0.1304 (all

data).

[4]

[5]

[6]

Compound 12: The crystals were grown from hexane. Crystal data

and details of experiment are T = 200 K, a = 10.478(2), b =

11.330(3), c = 15.764(4) Å, V = 1871.6(7) Å³, Pbca, Z = 7, D_C

=

1.173 gcm^–3, µ = 0.078 mm^–1, 2.95 Ͻ θ Ͻ 26.42°, I_hkl(coll/uniq)

17410/1920, R_int= 0.0671, Goof = 1.166, R1 = 0.0651, wR2 =

0.1583 (I Ͼ 2σ_I), R1 = 0.0735, wR2 = 0.1628 (all data).

Nitronyl Nitroxide 9a, Formamide 10, Imino Nitroxides 11b–11e,

11g, 11i, and 11j: ORTEP diagrams and X-ray crystallographic data

are provided in the Supporting Information.

[7]

[8]

CCDC-668098 (for 4a·H₂O), -710697 {for [Cu(hfac)₂]₃(5a)₂},

-710698 (for 5b), -710699 (for 6a), -710700 (for 9a), -710701

(for 10), -683982 (for 11b), -710702 (for 11c), -710703 (for 11d),

-683983 (for 11e), -718643 (for 11g), -683985 (for 11i), -683986

(for 11j), and -668099 (for 12) contain the supplementary crystallo-

graphic data for this paper. The data can be obtained free of

charge from The Cambridge Crystallographic Data Centre via

www.ccdc.cam.ac.uk/data_request/cif.

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At ν(MnO₂)/ν(1a) = 3:1, the oxidant completely transformed

into brownish black MnO(OH) according to general equation:

1 + 3MnO₂= 2 + 3MnO(OH). The IR spectrum of MnO(OH)

contained a set of characteristic absorption bands: ν = 570,

˜

1100, 2000, 2700, 3400 (broad) cm^–1(T. Kohler, T. Armbruster,

E. Libowitzky, J. Solid State Chem. 1997, 133, 486–500).

E. V. Tretyakov, V. I. Ovcharenko, R. Z. Sagdeev, D. V. Stass,

G. V. Romanenko, A. V. Mareev, A. S. Medvedeva, Russ.

Chem. Bull., Int. Ed. 2007, 56, 2043–2047.

Supporting Information (see also the footnote on the first page of

this article): Temperature dependencies of the effective magnetic

moments, ESR spectra, IR absorption bands, Crystal data and de-

tails of X-ray experiments.

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Acknowledgments

The authors are indebted to Dr. A. I. Kruppa for his help in inter-

preting the ESR spectra. Financial support by the Russian Founda-

tion for Basic Research (grants 09-03-00091, 08-03-00025, 08-03-

00038), the Russian Academy of Sciences, Siberian Branch of the

Russian Academy of Sciences, and the Program for State Support

of Leading Scientific Schools of the Russian Federation (Grant

NSh-1213.2008.3) and by Rinnert GmbH is gratefully acknowl-

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Received: December 13, 2008

Published Online: April 8, 2009

Eur. J. Org. Chem. 2009, 2548–2561

www.eurjoc.org

2561

Article Doi

New cascade syntheses of nitronyl nitroxides and a new synthetic approach to imino nitroxides

DOI: 10.1002/ejoc.200801237

Source and publish data:

Authors:

Article abstract of DOI:10.1002/ejoc.200801237

Full text of DOI:10.1002/ejoc.200801237

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