SU940471A1 - Process for preparing 4-haloalkyl derivatives of 3-imidazoline-3-oxide - Google Patents

Abstract

The method of producing 4-haloalkyl derivatives of 3-11M1LAZOL11N-3-OKSVDA general formula EXCH .0 HjC СНЗ ЩС N СН 3, T where, Alk, В g; G; , Alk, characterized in that the compound of the general Formula RCH2 is N., H, C, N cn. 4 where the values of R are as indicated above, and Alk or OH is reacted with bromine or iodine in an alcohol medium in the presence of anhydrous acid at a temperature of 0-20 seconds. 2. A method according to claim 1, characterized by the fact that dry hydrogen chloride or trifluoroacetic acid is used as an aqueous acid. 3. The method according to claims 1 and 2, about 1 TL and that in the case of The 4-bromoalkyl derivatives of the process are carried out for 10-60 minutes of 4ib 4. The method according to claims 1 and 2, this is because in the case of 4-yodoalkyl production X, the process is carried out for 20-30 hours.

Description

NeoG; reten e (i JIOCHTCH) to a new method of obtaining both new and new 4-th alcohols, iftrx 3rd MFA a50 3 oxides of Lormul1 1

RXCfi 0

where R «H (Alk, Br;

, 3;

 Alk ,,.

In the case of a compound, it is a stable nitroxyl radical. Compounds of this class are used as stabilizers of antioxidants, stress sensors, working substances, and kzanton generators. Nitroxyl radicals are especially widely used as spin labels in biological research, with spin labels most commonly used as local agents.

Gagshid s :; Kil Ni Tr o n a gruppi r o w a,

Mopec / Le 4 haloapkilimegt a c

third-party 3-and-2 dazolin-3-oxide-B, possesses, moreover, - Use these soydin1: m to obtain a hybrotic b from the assortment of stable -trox5-shY1Y from radicals with different functional iibiMH groups,

Derivatives of 3-imidazolin-3-oxide-sp, soderculos-C functional groups, capable of forming chelates with coxD.siieHHe: - radical delggra and psto-chg, can be used in ana: 1 l V b -1 e cc o fi lh mi If,

Combined with the M-alkyl group () i-iV.HC to consider how protechnological strengths are radical l5 so that the kiln group in the space of hindered amines during oxidation allows to generate nitroxylHoftra, a wild center Protected electrical spin tags can be used in the synthesis nitroxyl radicals that are inaccessible with the use of the call - -: radicapic precursors of B, .- also for the synthesis of latent spiges; pg; l labels intended for -; /: 5O .-:.; conditions that are not; .. c, i lizaat a radical center (the radical can be generated olislAchv: try directly .S asiivne WF-spectrometer), for example, as labels that control the L: reduction of water and oil -hgh TOK, t-for oilfield geophysics,

. The method of producing 4-halocdilkylgfshdazolinoxides containing the Kitrock radial center, including oxidation of the 1-hydroxy-3-imidaeoline-3-oxide with lead dioxide in benzene or ether and bromination of the nitroxyl radical with N-bromo-sulfide with amide using 0x-0x-3-x-3-oxydromoleacidol in the benzene or ether, and the heart of the nitroxyl radical containing N-bromo-3-oxide with lead dioxide in benzene or ether should be stored in a 0-halogen-carbon-4-halo-dimethylchloride; as the initiator of the decomposition of N-bromosuccinimide l.

The disadvantages of this method are: the presence of an oxidation stage, which reduces the yield of the desired products; the need to use toxic lead dioxide and costly N-bromosuccinimide; the heterophase nature of the bromination process, 3 connections to the check, the yield of the target product depends on the degree of grinding of the bromide of the agent and the speed of stirring of the reaction mixture.

In addition, the well-known method has been limited by the possibility of introducing atoc-5c in buok and chlorine into the molecule, while the most active ones are alkylating; these are iodine derivatives 2 J.

The aim of the invention is to simplify — i.e., the process of synthesis and the expansion of the range of products: imidazoline oxide.

This goal is achieved by the described method for the preparation of 4-haloalkyl derivatives of 3-imidazolin 3-oxide of the general formula (1); I conclude that the connection of the general formula

Ksb oh

- CH. X x

NCV to SM

3

I

where the value of ad of the radical R is described above, and, Alk and. OH, is subjected to 73 interaction with bromine or iodine i alcohol in the presence of anhydrous: oh acid, mainly from hydrochloric acid: laurist hydrogen or trifluoroacetic acid, at a temperature

O-ZO-Cj will prevail; naturally, 10-60 minutes in the case of nonir ieJinn 4-bromoalkylproducedLgx or, typically, 20-30h39, in the case of the reaction of 4-yodoalkyl derivatives of 3-imidazole-3-oxyl, the oxidative capacity of the halogens allows for the starting compound of general formula (IJ) avoids the oxidation stage with lead dioxide. Example. 4-} 5-methyl-1, 2, 2 5,5-pentamethyl-3-imidazolin-3-oxide B 100 MP of methanol saturated with HCl, dissolved 17 g (0.1 mol) 1,2,., 4,5 , 5-hexamethyl-3-imidazolin-3-oxde and 5.1 ml (0.1 mol) of bromine are added. The reaction mixture is evaporated, the residue is washed with 100 ml of chloroform. 4-bro.mmethyl-1,2,2,5,5-pentamethyl-3-imidazoline-3-oxide hydrochloride is obtained with a yield of 90%. To obtain the free base, Wg of the hydrochloride is dissolved in 100 ml of water, adjusted in% -iibiM KOH to pH 7 and extracted with chloroform. The extract was dried with magnesium sulfate, and chloroform was distilled off. Yield 85%. M.p. 79-80 ° C; UV spectrum (alcohol) ,, r260 (3.78) IR spectrum (KRr): 1590), 2Г, 20 (N-СНз); PMR spectrum (CDCl1): 4.60 (€ N2); 2.36 (N-CHj 1.A2 (2CH J, 1.31 (2SIA). Found:% C, 8; H, 7.1; N 11, Br, 32.5; CdH N. OBr. Calculated, %: C 3 ;; H 6.8; N 11, 2; Pg 32.1.. 11 Example 2. 4-Dibromomethyl-1, 2.2.5.5-ischtamethyl-3-imidazolin-3-o-k. a solution of 8.5 g (0.05 mol) of 1,2,2,4,5,5-hexamethyl-3-imidazoline 3-oxide in 100 ml of methanol, saturated with HCl, was added 5.1 ml (0.1 mole) of bromine. The reaction mixture is evaporated, the residue is dissolved in 100 ml of water, adjusted to pH 7 with 10% sodium bicarbonate solution, and the precipitated product is filtered off. Yield 97%. mp. 145-147 ° C; UV -spectrum (alcohol): LMoi: 2b7 (): IR spectrum (KVg): 1580 (), 2820 (L – CH3); spectrum of GOG (CDClj): 6.52 (CH); 2, 3b (J – C e), 1, (2СНз), 1.42 (2СНз). Found,%: 33 ,; H 4.9; N 8.1 Vg 49.0; CqH gN20Br2. Calculated,%: 32.8; H 5 , 2; N 8.5; Br A8.9. Example 3. 4-Iodomethyl-1,2, 2,5,5-pentamethyl-3-imidazolin-3-oxide. To a solution of 8.5 g (0.05 mol) 1,2,2,4,5,5-hexamethyl-3-imidazolin-3-oxide in 100 ml of methanol, saturated, no, 25.4 g of iodine in 150 ml of ethanol are added. The mixture is stirred for 24 hours, evaporated. The residue is dissolved in 100 ml of water, 10% sodium thiosulfate solution is added to decolorizing, brought to pH 7 with 10% sodium bicarbonate solution and extracted with chloroform. Suat extract with magnesium sulfate, chloroform is distilled off. T.sht. 42-45 0; UL-spectrum (alcohol) .26P (3.90); IR spectrum (KVg): 1590 (), 2820 (N-СНз). NMR (CDClj) spectrum: 4.29 (CH), 2.36 (N-CH.), 1, 3b (2CH3), 1.29 (2CH.). Found,%: C 36.2; H 5.3; N 9.7; 3, Calculated,%: C) H 5 ,; N 9.5; 3, 6. EXAMPLE 4. 4-Bromomethyl-2,2,5,5-tetramethyl-3-imidazolin-3-oxide 1-oxyl. To a suspension of 1.72 g (0.01 mol) of 1-hydroxy-2,2,4,5,5-pentamethyl-3-imidazolin-3-oxide in 50 ml of methanol, 0.7 ml (0.015 mol ) bromine. The mixture is stirred for 30 minutes, adjusted to pH 7 with 10% KOH, the KBr precipitate is filtered off and the filtrate is evaporated. The residue is dissolved in 50 ml of water, extracted with chloroform, the extract is dried with magnesium sulfate, and the chloroform is distilled off. Exit 63%. M.p. 122-123 s; IR spectrum: 1580 (); UV spectrum: L. 262.01); EPR: triplet 1: 1: 1; aN 14.5 E. Found,%: C 38, b; H 3.5; N 11.3; Br 31.9. VG NAO, Calculated,% С 38 ,; H 5.6; N 11.2; Br 32.0. EXAMPLE 5 4- (. Omethyl) 2, 2.5, 5-tetramethyl-3-imidazol-3. OXID-1-OXYL. Obtained by bromination of 4-ethyl 3-imidazolin-3-oxide-1-oxyl or

1-hydroxy-3-ethyl-3 imidazolin-3-oxide under the conditions of Example A.

Yields 70%,

M.p. Software-P2 C;

UV spectrum: 2BO (3.91);

IR spectrum: 1585 ();

EGTR: triplet 1: 1: 1;

Found,%: C 0.8; H 6.0; N 10.5; Br 30.2; CgH gBrNgOo.

Calculated,%: С .Э; H b, 1; N 10.6; Br 30.3.

EXAMPLE 6 4-Dibromomethyl 2, 2.5 (5-tetramethyl-3-imide zoline-3-oxide-1-oxyl.

to the suspension, 72 g (0.01 ml) of 1-hydroxy 2 5254.55 5-pentamethyl-3-imidaeolin-3-oxda in 50 ml of methanol with stirring was added lj, 3 m (0.025 mol) of bromine, kept at room temperature temperature of 2 h and cooled to, the precipitated precipitate is filtered off, washed with methanol. Yield 50%.

M.p. 135-137 0;

UV spectrum: LD, COP 262 (3.92);

IR spectrum: 1580 ();

EPR: triplet: 1; one

Nadno%: C 29.3; H 3.9; N 8, Br, 5;

,

C, 29.2; H 4.0;

Calculated,% M 8.5; Br kB, 6,

When brominated under the conditions of this example, a nitroxyl radical (with a ratio of reagents: 2), dihydromomethyl-3-imidazoline 3 oxide-I ™ oxyl is formed with a yield of 50%.

Example 7. 4-Bromomethyl 3-imidazolin-3-oxide-1-oxyl is prepared with bromideme 2,2,4,5, 5-pentamethyl-Zimi; g:; - o, gshn-3-oxide-1-oxyl under the conditions of Example 4 (with a ratio of reagents.}} and using 0.5 ml of triLuoroacetic acid as a catalyst, 65% flow.

Thus, the proposed method allows using a simple operation to obtain with a good yield a wide class of compounds - derivatives of 3-imidazolin-3-oxide.

In contrast to the known method, in the previous method, the oxidation stages, the use of toxic lead dioxide and the expensive and hard-to-reach N-bromosuccinimide are excluded. Substantially simplified basic conditions; reaction. In addition, it is shown that the process is equally successful both in the medium saturated with hydrogen chloride and in the presence of initial small amounts of anhydrous strong acids for the cases of the starting compounds of general formula (P), the necessary acidity of the medium develops due to the division of HBr in the oxidation of the hydroxy group.

The method is distinguished by mild reaction conditions, which allows the use of compounds of complex structure as starting materials.

In the proposed method, the reaction proceeds in a homogeneous medium, the elimination of heterogeneity allows working with large quantities of substances;

Claims (4)

METHOD FOR PRODUCING 4-HALOALKYL DERIVATIVES 3-IMIDAZOLIP-3-OXIDE of the general formula of the axis n ₃ with sn ₃ sn ₃ where R = H, Aik, V g; X = 8g, I; Y = 0, Aik, where R values are indicated above, and Y '= 0 ° Aik or OH, is reacted with bromine or iodine in an alcohol medium in the presence of anhydrous acid _c at a temperature of 0-20 ° C. S 2. The method of pop. 1, due to the fact that dry hydrogen chloride or trifluoroacetic acid is used as anhydrous acid. 3. The method according to pp? 1 and 2, with the exception that in the case of obtaining 4-bromoalkyl derivatives, the process is carried out for 10-60 minutes. 4. The method according to PP. 1 and 2, t on the case of the fact that in the case of obtaining 4-iodoalkyl derivatives, the process is carried out for 20-30 hours SU ,,,, 940471