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https://doi.org/10.29013/AJT-21-5.6-13-17
Yuldasheva Mukhabbat Razzoqberdiyevna, Doctor of Chemical Sciences, the Faculty of Chemistry National University of Uzbekistan, Uzbekistan E-mail: ymuxabbat@bk.ru Turayev Sherzod Baxodirovich, PhD student, the Faculty of Chemistry National university of Uzbekistan, Uzbekistan E-mail: sherzodbaxodirovich@mail.ru
THE SYNTHESIS OF PHTHALIMIDOMETHYLIC ETHERS OF ALIPHATIC CARBOXYLIC ACIDS
Abstract. Amidoalkylating reagents containing the phthalimide group are used in the synthesis of difficult to obtain primary amines and complex heterocyclic compounds. These types of amidoalkylating compounds are a suitable reagent for nucleophilic substitution reactions in acidic environments due to their resistance to acids. Reactions of amidoalkylating reagent N-hydroxymethylphthalimides with aliphatic carbonic acids were also carried out in benzene solvent and sulfuric acid catalyst. It was found that the yield of products obtained with N-hydroxymethylphthalimide was lower than the yield of reaction with N-^-hydroxyethylphthalimide. The structure of the obtained compounds was proved by analysis of their IR and NMR'H spectra.
Keywords: N-hydroxymethylphthalimide, haloacetic acid, halogen acetic acid ester, amidoal-kylation.
Introduction
Phthalimides are imide derivatives of phthalic anhydride and are widely used in both industry and pharmaceuticals. Phthalimides belong to the group of cyclic imides and have the characteristic chemical properties of two carbonyls bound to common nitrogen. Among cyclic non-aromatic nitrogen heterocycles, phthalimides are an interesting class of compounds that are widely used. Phthalimide contains a functional group of imides and can be considered as nitrogen analogues of anhydrides or diacyl derivatives of ammonia. Such compounds are obtained as a result ofvarious organic synthetic processes [1, 2-4], [2, 2-6].
The chemistry of heterocyclic compounds is one of the most complex branches of organic chemistry. Heterocyclic compounds play an important role
in biological processes, and researchers are trying to understand the chemistry of heterocyclic compounds to improve the quality of daily life [3, 1-2]. The structural diversity and biological importance of nitrogen-containing heterocyclic compounds have made them attractive targets for synthesis over many years. The construction of highly structured heterocyclic compounds seems to be important and significant. 5-membered N-heterocycles are of particular interest in the pharmaceutical industry because they are found in the main constituents of several drugs. Among heterocyclic briquettes, phthalimides have special biological significance and have been noted as herbicides, insecticides, anti-inflammatory agents, and antioxidants [4, 1-5]. Typically, in organic synthesis, they are used as starting materials and intermediates for the synthesis of various bioactive
compounds. The use of phthalimides as a group to protect primary amines has been extensively studied in the chemical literature, particularly for a-amino acids [5, 1-3]. Modified phthalimides are mainly used as organic building materials in organic synthesis and can be used in the preparation of bioac-tive compounds, i.e. antibacterial, analgesic, plant growth regulator, as well as in the dye industry [6, 1-4]. Typically, N-phthalimide derivatives are synthesized in many ways using reductions in organic solvents by condensing the amine with phthalic anhydride [2, 2-6]. Due to their favorable photophysi-cal and electrochemical properties, phthalimides undergo various high-efficiency photodecarboxylation reactions [7, 1-5].
These transformations have been used in the synthesis of biologically active additives as well as mac-rocyclic compounds. N-acetoxifalimides are multi-faceted representatives of imidyl and alkyl radicals by photodecarboxylation and have since been used for various binding reactions [8, 1-5].
It is possible to obtain esters with different biological activity through the amidoalkylation reaction of acids using hydroxyalkylimides, as well as to synthesize heterocyclic compounds with complex structure, in addition, primary amines, which are difficult to obtain [9, 1-4].
Therefore, chemists are particularly interested in the synthesis of esters of halogenic acids containing the phthalimide group and the study of its properties. We also carried out esterification reactions with N- (^-hydroxyethyl) phthalimide and N-methylol-phthalimide with monochlorine, mono bromine, mono iodic acid, trifluoric, trichloroacetic acid.
Research methods. In the synthesis of esters, amidoalkylation reactions of acids with methyllfalta-limide, which is occupied by the phthalimide group, were used. The course of the reactions and the purity of the product were checked on thin-layer chromatography. The structure of the obtained new substances was determined using PMR-spectroscopy, IR-, chromato-mass spectrometry.
For the experiments, the primary alcohol was synthesized in the literature according to certain methods:
NH + CH2O
H2O, 0c
NCH2OH
N-Methylolftalimide T , .= 136-138 °C, Rf =
' melting '
= 0,52 (silulfol system benzene: acetone = 3: 1).
We performed all the reactions in a round-bottomed flask equipped with a reverse cooler mounted on a tripod, a water collector, and a mechanical stirrer. The flask was filled with N- (hydroxymeth-ylphthalimide and carbonic acid (1: 1.1 ratio) benzene as a solvent and a small amount of sulfuric acid as a catalyst. The reaction was carried out by heating in a magnetic stirrer for 4-7 hours (until the calculated amount of water was separated). After the water separation was complete, the reaction mixture was cooled and water was poured over it. The precipitate from the mixture was filtered and separated. The substance was recrystallized.
Monobromoacetic acid phthalimidomethy-lephir is a white crystalline substance, yield 54%, T ,. = 78-80 ° C, Rf = 0.75 (silulfol, benzene-ace-
melting ' v '
tone system 3: 1). IR spectrum sm-1721, 798(d=C-H, ArH), 1496(vC=C, ArH), 3024,3061(vC-H), 1707, 3454 (nas-CO-NH-), 2962(nasCH2), 1749, 1771(n-CH2-COOR), 1169(n-C-O-).I2MR1H-spectr S= 4,4-7 ppm (2H, N-CH2), S= 2,9 ppm (2H, 2BrH2), S= 6,7-7,25 ppm (4H, ArH).
Monochloroacetic acid phthalimidomethy-lephir is a white crystalline substance, yield 59%,. T , = 87 °C, Rf = 0.81 (silulfol, benzene-ace-
melting ' v '
tone system 3: 1). IR spectrum sm-1 711, 726 (d= = C-H, ArH), 1383(vC=C, ArH), 2956(vC-H), 1717, 3488(nas-CO-NH-), 1405(nasCH2), 1717, 1782(n-CH2-COOR), 1138(n-C-O-). YaMR1H-spectr S= 3,2 ppm (2H, N-CH2), S= 5,3 ppm (2H, Cl-CH2), S= 6,70-7,25 ppm (4H, ArH).
Phthalimidomethylephyric monohydric acid 1703, 3437(nas-CO-NH-), 1390(nCH2),
is a light yellow crystalline substance, yield 43%, 1703,1770(n-CH2-COOR), 1247(n-C-O-).
Tmeltmg = 137 °C, Rf = 0.79 (silulfol, benzene-ac- PMR1H-spectr S= 4,47 m.u.da (2H, N-CH2), S= 5,37
etone system 3: 1). IR spectrum sm-1 725, 798 ppm (2H, J-CH2), S= 6,75-7,30 ppm (4H, ArH). (d=C-H, ArH), 1390(vC=C, ArH), 2957(vC-H),
O O
O
H2SO4
N—CH2-OH + HO—C— X ^
benzene
-H2O
O
N-CH2-O—C—X
X=-CH2Cl, -CH2Br, -CH2I
21
12I
Phthalimidomethylephir of trichloroacetic acid is a white crystalline substance, yield 49%, T ,. = 178 ° C, Rf = 0.68 (silulfol, benzene-acetone
melting ' v '
system 3: 1). IR spectrum sm-1 734,845 (d=C-H, ArH), 1667 (vC=C, ArH), 2963 (vC-H), 1704, 3467 (nas-CO-NH-), 1349(nCH2), 1772 (n-CH2--COOR), 1165(n-C-O-). NM^H-spectr S= =5,01 ppm (2H, N-CH2), S= 6,8 ppm (2H, O-CH2), S= 6,7-7,3 ppm (4H, ArH).
O
O
Phthalimidomethylephir of triphosphoric acid is a white crystalline substance, yield 50%, T =
melting
=92-93 °C, Rf = 0.84 (silulfol, benzene-acetone system 3: 1). IR spectrum sm-1 712 (d=C-H, ArH), 1706 (vC=C, ArH), 1720, 3485 (nas-CO-NH-), 1304(nCH2), 1720 (n-CH2-COOR), 1146,1091(n--C-O-). NMM-spectr S= 4,47 ppm (2H, N-CH2), S= 6,73 ppm (2H, O-CH2), S= 6,7-7,25 ppm(4H, ArH).
O
O
H2SO4
N CH2 OH + HO C X —
c
O X=-CCl3, -CF3
Results and discussion
The substituent nature of carbonic acid is important in the production of carbonic esters. If the substituent has an electron donor property, the positive charge value on the carbon atom of the carboxyl group decreases and O-nucleophilic ex-
vinegar pKa = 4.76, capril pKa = 4.88, chlorinated pKa = 2.86, dichlorvinegar pKa= 1.29, triftorvinegar pKa = 0.23, As a result, the penetration of the amidoalkylat-ing reagent is facilitated. This means that in acetic acid held by strong acceptor atoms, o-nucleophil
benzene -H2O
N CH2 O C X
C O
change becomes difficult. We know that monochlo-roacetic acid reacts more easily than acetic acid. This is due to the increase in the value and acidity of the positive charge of carbon in the carboxyl group when a single hydrogen in acetic acid is substituted for chlorine:
propion pKa = 4.88, adipine 1) pKa = 4.42, 2) pKa = 5.28, brominated vinegar pKa = 2.86, trichlorvinegar pKa= 0.65, tribromvinegar pKa = 0.66. substitution is easier than in other homologues and the yield is higher. As the ether formation is reversible, the release of water from the reaction
medium is also important as the equilibrium shifts to the right. The amidoalkylating reagent N-ß-hydroxyethylphthalimide can also form oxon comO
n-ch2-ch2-oh + h '
plex ions and decrease nucleophilic properties under the influence of large amounts of catalysts or proton solvents, such as primary alcohols:
O
O
Hence, aproton solvents or solvents that remove water as an azeotropic mixture can be used for the nucleophilic substitution reaction. The use of benzene as a solvent in amidoalkylation reactions with N-^-hydroxyethylphthalimide gives good results. Synthesis of phthalimidoethyl ester of monochloric acetic acid is carried out under the conditions of the reaction of synthesis of O
c o
\ ii
N CH2 CH2 OH + HO C X
/ 2 2
C O
\ ä+ / N-CH2-CH2—O+
H
H
O
(3-acetoxyethylphthalimide, the complex ester is formed with 84% yield. If the resulting water is removed from the reaction medium using benzene, the product is found to be 98% productive. The ether yield of the complex formed by the production of monounsaturated acetic acid for the reaction is 82%, and the yield of phthalimidoethyle ether of trifluoric acetic acid is 83% [10, 1-4]: O
O
H2SO4
"benzene -H2O
n ch2 ch2— o C X
X=-CH2Cl, -CH2I, -CF3
There is also a slight decrease in the amount of acids with N-m ethylolftalimide (59%, 54%, 43%, esters formed by the reaction of halogenated acetic 50%, 49%): O
,C O
H2SO4
n—CH2- OH + HO—C— X ^
benzene -H2O
O
X=-CH2Cl, -CH2Br, -CH2I, -CCl3, -CF
n
21
l3,
3
O
K o
N-CH2-O—C—X
C O
As a result of the attraction of the electrons of the methylene group N-methylfthalimide to the two car-bonyl groups, the carbon-oxygen bond is weakened and the O-nucleophilic properties are reduced. As a result, it can be assumed that N-methylphthalimide reacts not as a primary alcohol but as a tertiary alcohol. Therefore, the amidoalkylation reaction of halogen acetic acids with N-methylolphthalimide under conditions selected for synchronous bimolecular
substitution was somewhat lower. The formation of esters can be considered as independent of the acidity of acetic acid products.
Conclusion
As a result of amidoalkylation reactions of car-boxylic acids with N-hydroxymethylphthalimides, phthalimidoalkyl esters of monochlorine, mono-bromine and monohydric acetic acid and phthalimidoalkyl esters of trifluoric trichloroacetic acid were
synthesized. It was shown that the yield of the synthesized esters was formed according to the nature of the reagents and solvent obtained for the esteri-fication reaction. It has also been shown that al-
though N-hydroxymethylphthalimide is a primary alcohol, it reacts with carbonic acids as a tertiary alcohol in its reactions in a benzene solvent.
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