RU1770322C - 2,2-dialkyl-2h-imidazole-1-oxides as intermediate compounds for synthesis of stable imidazoline radicals and a method of its synthesis - Google Patents

Abstract

The invention relates to heterocyclic compounds, in particular the preparation of 2,2-dialkyl-2H-imidazole-1-oxides of the general formula I 6RT N-CR2R3-Nt O) CH where Rv-3- see below, intermediates for the synthesis of stable imidazoline radicals used as antioxidants, antiknock agents, analytical reagents. The goal is to create a new method for producing new intermediates for the specified purpose. The synthesis was carried out by reacting approx. 6-100 ° C hydroxyminin methyl ketone with an aliphatic ketone and ammonium acetate in acetic acid, followed by isolation of the target product. Values of Ri, R2, Pz: yield,% t mp, ° C, gross: a) CeHs, CH3, CH3, 90, 108-109. CnHi2N20; b) Sat. CHS (CH2) -CH3, 60, oil, CieH2eN20; c) SBN3, CH3, CH2-C (0) OC2H5. 40.58-61, g) CeHs, СНЗ, СН2СН2С (0) ОСНз, 80, С14Н1б№Оз oil; e) SBN5. CH3, CH2-CH2-C (0) OH, 60, 107-109, Cl3HiNO3: e) CeHs. CH2CH2CH3, CH2CH2CH3, 67, 77-79, CisH2o # 0: g) CH3, CH3CH3, 63.27-29, CeHioN20; h) SNZ, SNZ. 60, 186-188, CeNd # 02; i) n-NOrCe H4, CH3. CHS, 56, 213-214. SpnpMzOz; j) CN, CHS. CHS, 75, 43-45. l) C (0) OCH3, CH3, CH3, 68. 80-82, StNyMaOz; m) C (0) NH2, CH3. CHS 68.204-206. SbNdM302; m) p-H2M-CeH4. CHS CH3, 22.188-190, CuLZMzO. New substances are more accessible than known ones. tn C

Description

The invention relates to new chemical compounds, namely 2,2-dialkyl-2H-imidazole-1-oxides of the formula (I), wherein Ri. R2 and RS have the following meanings:

 I

and).

b),, R2 (CH2) 7CH3

at). . Нз СН2СООС2Н5

d). Rz СН2СН2СООСНз

e). R3 CH2CH2COOH

e), R2 Ra CH2CH2CH3

g)

h), i) Rv n-02NC6H4, k),

l) Ri COOCH3,

m) Rt CONH2.

m) Ri n-H2NCeH4.

2.2-Dialkyl-2H-imidazole-1-oxides of the indicated structure containing the aldonitron group in the composition of the heterocycle can be used as intermediates for the preparation of stable nitroxyl radicals

VI VI

ABOUT

With

Nd yu

imidazoline, which can be used as polymerization inhibitors, antiknock agents, antioxidants, radiation sensitizers, analytical reagents, groundwater movement indicators, spin tags and probes.

The purpose of the invention is the production of new 2,2-dia / yl-2H-imidaeol-1-oxides, which are intermediates for the preparation of stable nitroxyl radicals containing various functional groups, in a simple manner from the available starting hydroxyminomethyl ketones,

The invention is illustrated by the following examples.

Example 1. Obtaining 2,2-dimethyl-4-phenyl-2H-imidazole 1 -oxide (la).

A mixture of 1 g of hydroxymenemethylphonyl ketone, 5 ml of acetone, 5 ml of acetic acid and 3 g of ammonium acetate is boiled in a water bath under reflux for 2 hours, after which the reaction mass is diluted with 50 ml of water and extracted with chloroform 5 times 50 ml . The extract was dried. MgS04 chloroform was evaporated, the residue was chromatographed on a silica gel column, eluent - ether - hexane 1: 1. The resulting 2H-imidazole-1-oxide (la) was recrystallized from a 1: 1 ethyl acetate-hexane mixture. Yield 1.14 g (90%), mp. 108-109 ° C. PC spectrum (KBr), v, 3090 (), 1520, 1580 (. UV spectrum (ethanol), I max., Nm, (Ig e): 237 (4.30) 280 (4.24). PMR spectrum in (b, ppm: 1.53, 6H, s, (Hem. CH3), 7.60, 3H, m, 8.10, 2H, m (CeNb). 8.10. 1N. s, ( )

Found,%: C 70.1; H 6.3, N 14.9

SizhaMaO

Calculated,%. C 70.2; H 6.4; N, 14.9.

Example 2. Preparation of 2-methyl-2-octyl-4-phenyl-2H-imidazole-1-oxide (Ib).

A mixture of 1 g of hydroxymininomethylphenyl ketone, 5 ml of decanone-2, 5 ml of acetic acid and 3 g of ammonium acetate is heated in a boiling water bath for 4 hours, after which the reaction mass is diluted with 50 ml of water and extracted with chloroform 3 times in 20 ml. The extract was dried with MgSO3, chloroform was evaporated, the residue was chromatographed on a column of silica gel, the eluent — ether — hexane 1: 1. 2H-imidazole-1-oxide (b) is obtained as a slightly brownish oil; yield 1.2 g (60%). And K spectrum (CCU), V, cm 1: 3080 (H), 1580, 1520 (). UV spectrum (ethanol), I Max, im, (Ig Ј): 237 (4.25), 280 (4.17). PMR spectrum in (SOzCO, d, ppm: 1.60, ZN, s, (2-СНЗ), 0.83, ZN, m, 1.20, 12N.m, 2.03, 2N m, ((СНа) 7СНз), 7.50, ЗН, m, 7.83, 2Н.m, (СеНб), 7.77, 1H, s. ().

Found,%: C 75.5; H 8.9; N 9.3

СшН2б№0

Calculated,%: C 75.7; H 9.2; N, 9.8,

Example 3. Preparation of 2-methyl-4-phenyl-2-ztoxycarbonylmethyl-2H-imidazole-1-o x ida (I c).

A mixture of 1 g of hydroxyiminomethylphenyl ketone, 3.5 ml of acetoacetic ester, 5 ml of acetic acid and 3 g of ammonium acetate is heated in a boiling water bath for 4 hours, after which the reaction mixture is diluted with 50 ml of water and extracted with ethyl acetate 5 times 50 times ml The extract was dried with MgSO3, ethyl acetate was evaporated, the residue was chromatographed on a silica gel column, eluent-ether. The resulting 2H-imidazole-1-oxide (Is) is recrystallized from a 1: 3 ethyl acetate-pentane mixture. Yield 0.7 g (40%), mp. 58 - 61 ° C. PC spectrum (KBr), V,. 3090 (N-C-H), 1730 (CO), 1570, 1510 (). UV spectrum (ethanol), A max., Nm, (Ig e :): 234 (4.18), 282 (4.12). 1 H-NMR spectrum in CDCIs, b, ppm: 1.12, 3H, t, 4.07 2H, q, 3 Hz, (CzHg), 1.67, 3H. s, (CH3), 3.08, 2H, s, (CH2), 7.53, 3H, m, 7.87. 2H, m, (CeHs), 7.80, 1H. with. (). Found,%: C 64.3; H 6.3; N 10.4

ScN1b№Oz

Calculated,%: C 64.9; H 6.2; N, 10.8.

Example 4. Preparation of 2-methyl-2- (2-methoxycarbonitrile) -4-phenyl-2H-imidazole-1-oxide (Id).

A mixture of 1 g of hydroxymininomethylphenyl ketone, 4 ml of levulinic acid methyl ester, 5 ml of acetic acid and 3 g of ammonium acetate is heated in a water bath for 4 hours, after which the reaction mass is diluted with 50 ml of water and extracted with chloroform 3 times in 20 ml. The extract was dried with MgSCM, chloroform was evaporated, the residue was chromatographed on a silica gel column, and the eluent was ether. 2H-imidazole-1-oxide (g) is obtained as a yellowish oil. Yield 1.4 g (80%). PC spectrum (CCI4), v, 3080 (ISHC-H). 1740 (СО), 1570, 1510 (). UV spectrum (ethanol), I max., Nm, (Ig e:): 237 (4.21), 282 (4.13). PMR spectrum in CDCIs, b, ppm: 1.62, ЗН, s, (СНЗ), 2.27, 4Н, m, (СН2СН2), 3.57, ЗН, s, (ОСНз). 70.53, ZN, m. 7.90, 2H. m, (CeHg), 7.90, 1H, s, ().

Found,%. C 64.3; H 5.7; N 10.5 С14 Жб№Оз

Calculated,%: C 64.9; H 6.2; N, 10.8.

Example 5. Obtaining 2-methyl-2- (2-carboxyethyl) -4-phenyl-2H-imidazole-1-oxide (d).

A mixture of 3 g of hydroxymininomethylphenyl ketone, 9 g of levulinic acid, 20 ml of acetic acid and 9 g of ammonium acetate is heated in a boiling water bath for 4 hours, after which the reaction mass is diluted

150 ml of water and extracted with chloroform 5 times in 60 ml. The extract was washed with a saturated solution of N32C03 50 ml times. aqueous extracts are combined and neutralized with 20% sulfuric acid. The resulting solution was filtered through a paper filter and again extracted with chloroform 5 times in 50 ml. The extract was dried with MgSCM, chloroform was evaporated, the residue was triturated with dry ether. The resulting precipitate of compound (e) is recrystallized from ethyl acetate-hexane CHI. Exit - 3 g (60%), mp 107-109 ° C. IR spectrum (KBr), v, 3090 (), 1695 (CO), 1570, 1510 (C-N). UV spectrum (ethanol), I max,, im, (Ig e): 236 (4.22), 238 (4.15). PMR spectrum in CDCI3, b, ppm: 1.63, ZN, s, (CH3). 2.23, 4H, m, (CH2CH), 7.50, ZN, m, 7.87, 2H. m, (SBN5). 7.87, 1H. s, (), 10.23, 1H, broad, (OH).

Found,%: C 63.0; H 5.7; N 11.2

С1зН14№Оз

Calculated,%; C 63.4; H 5.7; N, 11.4.

Example 6. Obtaining 2,2-dipropyl-4-phenyl-2H-imdazole-2-oxide (le).

A mixture of 1 g of hydroxymininomethylphenyl ketone, 4 ml of dipropyl ketone, 5 ml of acetic acid and 3 g of ammonium acetate is heated in a boiling water bath for 5 hours, after which the reaction mass is diluted with 50 ml of water and extracted with chloroform 3 times in 20 ml. The extract was dried with MgS04, the chloroform was evaporated, the residue was chromatographed on a silica gel column, eluent ether-hexane 1: 1.2H - imidazole-1-oxide (1e) was recrystallized from hexane. Yield 1.1 g (67%), mp. 77-79 ° C. IR spectrum (KBr), v, 3080 (), 1570, 1510 (). UV spectrum (ethanol). I am max. , im, (Ig Ј): 238 (4.18), 280 (4.11). The PMR spectrum in SSC. b, ppm: 0.87, 10Н, m, 1.94, 4Н, m, ((СН2СН2СНз) 2), 7.50, ЗИ, m, 7.93, 2Н. m, (SBNb), 7.87, 1H, s, ().

Found,%: C 74.0; H 8.2; N 11.2

C15H20N20

Calculated,%: C 73.7; H 8.3: N 11.5.

Example 7. Obtaining 2,2,4-trimethyl-2H-imidazole-1-oxide (g).

A mixture of 2 g of hydroxyiminoacetone, 5 ml of acetic acid, 10 ml of acetone and 3 g of ammonium acetate was heated at reflux for 1 hour, after which the reaction mixture was poured into 100 ml of water and extracted with chloroform 5 times in 20 ml. The extract was dried with MgSO, chloroform was evaporated, the residue was chromatographed on a silica gel column, and chloroform was the eluent. The resulting 2H-imidazole-1-oxide (g) was sublimated at 2 mmHg. and 100 ° C. Yield 2.0 g (63%), mp. 27-29 ° C. IR Spectrum (CCU), v, 3130 (), 1605, 1520 (). UV spectrum

(ethanol) I'm max. nm, (Ig f): 283 (3.91). 1 H-NMR spectrum in CCk (3, ppm: 1.46, 6H. S. (2-CH3). 2.30, 3H, s, (4-CH3). 7.23, 1H, s, (N-CH ). Found,%: C 56.6; H 8.4; N 22.2

SatNu # 0

Calculated,%: C 57.1; H 8.0; N, 22.2.

Example 8. Preparation of 4-hydroxyminomethyl-2,2-dimethyl-2 H-imidazole-1-oxy-yes (h).

A mixture of 2 g of dihydroxyiminoacetate, 10 ml of acetone, 1 ml of acetic acid and 3 g of ammonium acetate is heated in a boiling water bath for 1 h, after which the reaction mass is poured into 100 ml of a saturated NaCI solution and extracted with ethyl acetate 10 times in 30 ml. The extract is dried, the ethyl acetate is evaporated, 50 ml of heptane are added to the resulting mass and evaporated again. The residue was triturated with 20 ml ethyl acetate-hexac -1: 1, the precipitate of 2H-imidazole-1-oxide (h) was filtered off and recrystallized from chloroform. Yield 1.6 g (60%), mp. 186-188 ° C. IR spectrum (KBr), v, 3090 (), 1610, 1590, 1530 (). UV spectrum (ethanol), Yamax. nm, (Ig e): 231 (4.50), 292 (4.04). PMR spectrum o (С0з) 250, 6, ppm: 1.43, 6Н, s, (Gem. СНЗ), 7.73, Ж, s, (О), 7.97, 1Н, s, ( ), 12.43, 11-1, ush, (OH).

Found. %: C 46.5; H 5.9; N, 27.4

SbN9№02

Calculated,%: C 46.5; H 5.9; N27.1.

Example 9. Obtaining 2,2-dimethyl-4- (4-nitrophenyl) -2H-imtsdazole-1-oxide (s).

A mixture of 3 g of p-nitroisonitrosoacetophenone. 25 ml of acetone, 9 g of ammonium acetate and 15 ml of acetic acid are refluxed for 1 hour. The reaction mass is cooled to 20 ° C, the precipitate of the compound (s) is filtered off and recrystallized from ethanol. Yield 2.0 g (56%), mp. 213-214 ° C. IR spectrum (KBr), V, 3100 (), 1520.1350 (N02). UV spectrum (ethanol), Yamax. nm, (Ig s): 282 (4.41). PMR spectrum in, d, ppm: 1.67, 6H, s, (Gem. CH3), 7.87, 1H. s, (), 8.17, 8.43, AA BB, Hz, (CcHU).

Found,%: C 56.7; H 4.0; N 18.1 CiiHnN303

Calculated,%: C 56, and; H 4.8; N, 18.0.

The following examples illustrate the synthesis of compounds (ki) by chemical modification of functional groups in the molecules of the compounds (ia-n):

Example 10 Preparation of 2.2-Dimegyl-4-cyano-2H-imidazole-1-oxide (k).

20 ml of triethylamine are added to a suspension of 6 g of compound (h) in 100 ml of chloroform.

and stirred until complete dissolution. 8 g of n-toluenesulfonyl chloride are added in portions to the resulting solution. After 0.5 h, the reaction mass was washed thoroughly with saturated NaCl and dried with MgSCM, and the solution was evaporated. Compound (1k) was isolated by column chromatography on silica gel, eluent — chloroform, and sublimated at 10 mm Hg. and 80 ° C. Yield 4.0 g (75%), mp. 43-45 ° C. IR spectrum (KBr), v, 3150 (N-C-H), 1660, 1495 (). UV spectrum (ethanol), A, nm, (Ig e): 315 (3.57), 243 (2.78). PMR spectrum in SSC, d, ppm: 1.60, 6H, s, (Gem. CH3), 7.45, 1H, s, ().

Found,%: C 52.3; H 5.2; N 30.2

CeHyNoO

Calculated,%; C 52.5; H 5.2; N, 30.6.

Example 11. Obtaining 2,2-dimethyl-4-methoxycarbonyl-2 H-imidazole-1-oxide (Il).

To a solution of 0.6 g of compound (1k) in 40 ml of methanol is added 1 l of triethylamine. After 4 hours, the solution was evaporated, 10 ml of methanol were added, and 2% hydrochloric acid was added dropwise to. The methanol is evaporated, the residue is extracted with chloroform 3 times in 5 ml. The extract was dried with MgSO4 and evaporated. The resulting compound (1 L) was recrystallized from a 1: 1 ethyl acetate-hexane mixture. Yield 0.5 g (68%), mp 80-82 ° C. IR spectrum (KBg), t, CM 1: 3100 (), 1730, 1750 (СО), 1510, 1590 (). UV spectrum (ethanol), I, nm, (Ig Ј): 310 (3.52). 1 H-NMR spectrum in CDCIs, b, ppm: 1.60, 6H, s, (Gem. CHs), 4.02, 3H, s, (OCHs), 7.55, 1H, s, (),

Found,%: 49.6; H 6.0; N, 16.4

C7NuoOz

Calculated,%: C 49.7; H 6.0; N, 16.6.

Example 12. Obtaining 2,2-dimethyl-4-carbamoyl-2H-imidazole-1-oxide (1m),

To a solution of 0.2 g of compound (1 L) in 3 ml of ethanol is added 3 ml of 250 aqueous ammonia. After 0.5 h, ethanol was evaporated, the residue was extracted with chloroform, the extract was dried with MDSM, and evaporated. The resulting compound (1m) was recrystallized from etml acetate. Yield 0.15 g (68%), mp. 204-206 ° C. PC spectrum (KBr), v, 34300, 3320, 3270, 3190, 1605 (NH2), 3140 (), 1680 (СО), 1585, 1510 (). UV spectrum (ethanol), d, nm. (1d Ј): 303 (3.69), 242 (2.30).

Found,%: C 46.2; H 5.8; N, 26.9; CeHgNaOa

Calculated,%: C 46.2; H 5.8; N, 26.9.

Example 13 Preparation of 4- (4-aminophenyl-dimethyl H-imidazole oxide (n)

To a suspension of 2 g of compound (s) in 50 ml of methanol are added 1 g of Raney Nz nickel and 3 ml of a 30% hydrazine solution and mix III

5 hours. The catalyst is filtered off, washed with hot ethanol, and the combined solution is evaporated. The residue was separated by silica gel column chromatography; chloroform was the eluent. The resulting compound (s) is sublimated at 2 mmHg. and 170 ° C. Yield O, 5g (22%), mp 188-190 ° С. IR spectrum (KBg), V, 3350, 2100, 1650 (МН2), 1590, 1530 (). UV spectrum (ethanol), I, nm, (Ig Ј): 365 (4.05), 300 (4.16), 263 (4.03).

Found,%: C 64.9; H 6.5; N, 21.1.

Cnhisnso

Calculated,%: C 65.0; H 6.5; N, 20.7.

Compared to other intermediates in the synthesis of nitroxyl radicals, such as compounds II and III

th $ b Ј &,

xi .on

where X OH, N

, AlK, Ar, Met ,,

Rs, RG. .

Newer compounds I are more accessible,

since the starting hydroxyximinomethyl ketones with different RI substituents are more accessible.

The invention can be used to synthesize valuable nitroxyl radicals.

Claims (1)

The claims 2,2-D nal kil-2 H-imidazole-1 oxides of the formula  , where a) Ri-CeHs, H22 Pz-CH3. b) Ri-CeHs, R2-CH3, R3- (CH2) 7CH3; c) Ri-CGH5, R2-CH3, R3-CH2COOC2H5, - d) Ri-CeHs, R2-CH3, R3-CH2CH2COOCH3 d) Ri-CeHs, R2-CH3, R3-CH2CH2COOH e) Ri-CeHs. R2 R3-CH2CH2CHa h) Ri-CH NOH, R2 R3-CH3; n) Ri-n-02NC6H4. R2 R3-CH3 characterized in that the hydroxyminomethyl ketones of the formula where RI has the indicated meanings, condensed with aliphatic ketones of the formula R3 where R2 and RS have the indicated meanings, and ammonium acetate in acetic acid at 56-100 ° C, followed by isolation of the target product.