SU453838A3 - METHOD OF OBTAINING DOUBLE BENCH HETEROCYCLIC ALCOHOLS - Google Patents

Description

The invention relates to a process for the preparation of new heterocyclic alcohols, which can be used for the preparation of heterocyclic triglpcidin compounds that are used in the production of resins.

There is a method for obtaining similar Syirts, for example,

CH5CHNz

about s-s-en-, n-, s-s-s about I I I I

CH-GSN-CH-L; L —C11.2- N N-CHrCK-Clij

he / s he

oh oh

which are used to prepare diplcide esters.

The proposed method for the preparation of two-leryt halogen alcoholic compounds of formula I

, e. ",%; - g

HN N-fflr Hr H

i. №I

Oj

where X is a divalent alkylene base; An R-hydrogen or an alkyl group containing 1 to 4 carbon atoms is that a compound of formula II

R

MI, /

is reacted with 1,3-dichloropropan-2-olam, having in group 2 R group, where R is hydrogen or an alkyl group containing 1-4 carbon atoms, or with an ephealogoyl group and isolating the target product by well-known techniques.

The method can be carried out following 11 techniques.

1 mol of the cycloureide of formula II is reacted with 1 mol of euhalohydrin in the presence of an alkali to obtain the corresponding roglycpdil. The resulting compound is subjected once again to the interaction with 1 mole of cycloreide formula P.

2 mol of the cycloureide of formula II are condensed from 1 mol of 1,3-dichloropropan-2-ol, which in group 2 is labeled R.

1 mole of cyclourend of formula II and 1 mole of halogen-hgpdrin are translated into the corresponding form my halogen-hgpdrpna p this

soydippepe codendensir

another 1 mole of the compound of Form II ly.

2 mol of cyclone-phase of formula IJ are condensed with I mol of epallogengdrna with hydrogen halide cleavage,

P p II .m er 1. 1,3-Bl1s- (5,

o-dimetplgidantonnl-Z) -nr011an-2-ol.

Into a 4-liter glass window with a broomstick, a thermometer, and an intensive cold box, a room temperature dial clock is served) 520 g of 95% by gas chromatographic screen (1,3-dichloropropan-2-ol) (3.83 mol), 981 g 99.5 % 5.5-dnmetnlgndanto11na (7.66 mol), 582

g of small-particle anhydrous calp carbonate (4.21 mol) and 960 ml of technical dimethylformamide. With slow unmixing, the porridge mixture is heated to 120 ° C, and the mixture becomes fluid. Then immediately the exothermic reaction of irn to a strong release of CO2 is started. The heating bath is removed and the porridge is stirred vigorously. After removing the heating bath

the temperature is below 124-126 ° C. After approximately 25-30 minutes, the exothermic reaction is stopped and the temperature of the reaction mixture is lowered to 116 ° C. For a better flow of the reaction, it is stirred for another 5 hours at 126 ° C and then the hot reaction mixture is filtered on a porcelain dish under suction in order to

detach potassium chlorpide.

The mixture is conceptualized to dryness in a rotary evaporation apiarate at 70-80 ° in a vacuum obtained using a water jet pump. The product is formed as a translucent, slightly yellow rasilawa, which crystallizes spontaneously. To remove volatile matter

it is dried at 90 ° C and 0.2 Torr to its minimum weight,

1212.6 g of a colorless or pale yellow crude crystallisate (calculated 1196.5 g) are obtained, which is crystallized at 142 ° C (Mettler FP 51). This raw product contains enie a small amount of potassium chloride and unreacted raw materials.

Iadeno,%: C, 46.8; H 6.5; N 16; ash 5.8.

Calculated,%: C 50.0; H 6.4, K 17.9.

Thus, the content of the desired bishydantoin in the raw product is approximately 86%.

For cleaning, the raw product can be crossed out of 550 g of water. 716.3 g of purified product are obtained (this corresponds to 60.6% of the calculated yield, in terms of non-dimethylgndantoin used).

The 1,3-bns- (5, 5-dimethylgndantoinyl-3) -ironon-2-ol 3,3-roxynroiylene) -5,5-dimethylhydantoin thus purified was melted at 178-181 ° C.

Paideno,%: C 49.5; H 6.4; N 17.6; ash 1.1.

Calculated,%: p. 50,0; H 6.4; N 17.9; ash.

EXAMPLE 2 1,3-Bis- (5, 5-dimethylpdantonyl-3) -iroan-2-ol.

A solution of 1 mol (185 g) 3H-glptsidl-5, 5-dk-metlgidantoina (epoxpd content of 5.4 epoxy equivalent per 1 kg) in 128 ml of dimethylformamide is stirred at 100 ° C. 128 g of dmethyl hydantoin is added in 30 min. The reaction is exothermic and therefore the heating bath is removed. The temperature then rises to 130 ° C. After termination of the exothermic reaction, stir for another 5 hours at 130 ° C. Then the clear light yellow reaction mixture is concentrated to dryness at 70 ° C in vacuum, obtained with the help of a water jet of the 1st pump, and the solution is sputtered with 150 ml of water. After drying the iris at 100 ° C in vacuum, 152.8 g of a small colorless crystalline base (49% of the calculated) are obtained, which is 185.6 ° C (Mettler FP 51).

An elemental analysis shows that ipo; iyKT is 1,3-bis- (55-dimethylphenhydinyl-3) -iropan-2-ol.

Paydeno,%: C 49.9; P 6.6; N 17.8.

Calculated,%: C 50.0; H 6.5; iN 17.9.

Example 3. 1,3-Bis- (55-dimethylhydantoinyl-3) -iropan-2-ol.

A solution of 640.5 g of 5.5-dimethylpdangoin (5.0 mol) and 3.0 g of potassium chloride in 600 ml of water are repositioned at 95 ° C. To this clear, colorless solution, 647.5 g of epichlorohydrin (7.0 mol) was added dropwise over 30 minutes, mixed again for another 240 minutes, and 97 °. Then the hot reaction mixture is filtered and the clear light yellow solution is completely concentrated in a rotary evaporator at 70 ° C in vacuum, obtained with a water jet pump. Then the mass is dried at 65 ° C n 0.15 Torr to a constant weight. 1103 g of a clear, slightly yellow high-viscous liquid (100% of the calculated) are obtained, which is recrystallized to a white crystalline mass. The purity of the product of Kta is 90.2% based on the chlorine test (found: 14.5% C1, calculated: 16.07% C1). The residue consists of starting materials. In addition, there is a small amount of 3-glipidyl-5,5-dmethylhydantoin, as revealed by eryoxide titration (found: 0.2 epoxy equivalent per 1 kg). The spectrum of irotopic magnetic resonance (60 MS H-NMR, detected in deuterochloroform CDCls irn 35 ° C relative to TMS tetramethyl plan) proves, thanks to the presence of the following signals, the correctness of the structure of the obtained product:

, 42: 6 protons (singlet):

I

SNS

-C HNZ

, 50-3.75: 4 protons (multiplet) 6 3.80-4.40: 2 protons (multiplet)

-en, - (; n-sn2-C1

he

, 7-7,2: 1 iroton (wide smiglet)

In addition, the mass spectrum proves the presence of the named structure by the presence of a molecular Iop at 221 units of mass (M + H) (calculated polar weight 220.7) and fragmentation at 205 units of mass (M-CH3), 184 units of mass (M -NS1), 177 mass units

(M-HNCO) and so on. A mixture of 489.5 g of an i-powder is higher than 90.2% of 3- (2-hydroxy-3-chloro-npropyl) -5,5-dimethylhydantoin (2.0 mol), 207.5 g 5 , 5-dimethylgidaitopia, 152 g of anhydrous small-fine potassium carbonate and 300 ml of dimethylformamide are heated with stirring oil to 120 ° C. Starts strong allocated 1e CO2. The reaction mixture is stirred for a total of 5 hours and 121 -. Processed as indicated in Example 1. As a raw product, 623.5 g of a colorless crystalline mass (99.8% of the calculated) are obtained, which contain the desired purity product of approximately 92% (calculated on the basis of elementary analysis). For cleaning, the product is recast from 310 ml of water. 465.0 g (this corresponds to 73% of the calculated) of a small, colorless crystallisate, which melts at 186-187 °, are obtained.

Found,%: C 49.6; H 6.4; N 17.6.

Calculated,%: C 49.9; H 6.4; N 17.9.

Thus, an i-product is obtained that is identical to that obtained in Examples 1 and 2 of 1.3-bis (55-dimethylhydantoinpl-3) - iropan-2-ol. The proton magnetization resonance spectrum (60 MS H-NMR, detected in DMSO D-S with respect to TMS) confirms, by the presence of the following signals, the structure of the semi-compound:

6 1.25: 12 Nrotop (singlet):

Sh.

N

/

CH-,

6 6 3.1-3.9: 6 protons (multiplet

N-CHj-CH-CHr OH

6 5.1-5.7: 2 irotons (shirokip singlet):

2 "lb

Example 4. 1,3-Bis- (5, 5-dimetn.1G11dantouinil-3) -2-metpliropan-2-ol.

As indicated in PREMER 3, 106.6 g of p-methylephichlorohydrin (1.0 mol) is reacted with 128.1 g of 5,5-dimethylhydroxyne in 140 ml of dimethylformamide using 1 g of lithium chloride as a catalyst. After adding dropwise the epoxide, the mixture is stirred for another 5 hours at 128-130 ° C. Processed as indicated in Example 1, 206 g (88% of the calculated) yellow and rosy very viscous solution are obtained as raw product, the purity of which is on the Ospovippe spectrum of nuclear radiation and electroanalysis 72%.

A mixture of 193.5 g of this crude 3- (2-hydroxy-2-met11L-3-chloro-propyl) -5.5-dimethylpentane (0.592 MOvTb), 62.8 g of fine-powdered anhydrous potassium carbonate, 125 ml of dimethylformamide and 75 , 8 g of 5,5-dimethylhydanto (on iO, 592 mol) are stirred for 10 hours at 125 ° C. Sachala and there is a strong selection of C02, which gradually ceases. Then the mixture is cooled to 80 ° C, 330 ml of water is added and the mixture is cooled with stirring to -5 ° C. Within a few hours, the desired product crystallizes out of the colorless precipitate. This precipitate is fi ltrated and dried with 70 ° C and 20 Torr to constant weight. 118 g (61% of the calculated) colorless powder is obtained, which melts at 162-164 ° C. The mass spectrum shows a molecular ion (M) multiplied by 1 iroton at 327 mass units, which corresponds to a molecular weight of 326.4. In addition, the following fragments can be set: 311 (), 309 (327-NaO), 308 (M-NgO), 293 (311-HzO); 185 (fragmentation between Ci and Bridge); etc. The proton magnetization resonance spectrum (60 MS H-NMR, in CDCla relative to TMS) also shows that the desired bishydantone is obtained:

6 1.10: 3 nrotons (singlet)

1% C-O

7 6 1.33-1.42: 12 protons (doublet)

N / SIS 2x СНз

6 2.90-3.10: 1 proton (multi-year)

W-E1

6 3.63: 4 protons (cartoon)

2% h; n26 5.1-5, /: 2 protons. (cartoon) N1 years)

2 "% H

PRIde 5. 5. 1,3-Bis- (5, 3-day. Methyl rpditoito-3) -prone 11-2-ol.

In a four-liter flask with a volume of 6 l with a stirrer, thermometer, reflux condenser II, the addition funnel is stirred at 110 ° C 1793 g 5,5-d11methylg11aptoina (14.0 mol), 1015 g of fine-powdered anhydrous potassium carbonate (7.35 mol), 10 g of chloride Kali and 1750ml of dnmetilformamnda. This mass is added dropwise in 1 liver to 90 minutes with a strong mixture of 712 g enhlorhydrin (7.7 mol). The reaction becomes exothermic. A strong COO release begins. The heating bath is removed. The temperature rises to 135 ° C. After iribavlepi, the exothermic reaction quickly ceases. Then it is stirred for another 5 hours at 125 ° C. The reaction mixture is diluted with 300 ml of dimethylformamide, filtered again and hot from potassium chloride and then concentrated in dryness in a rotary scrubber at 120 ° C in a vacuum, obtained by means of a water jet. The mixture is then dried at 120 ° C and 0.2 Torr to constant weight. 2307 g of raw product are obtained, which are recalculated from 1200 ml of water. . Receive 1351 g (62% of the calculation) of a colorless fine crystalline crystal (without processing the mother liquor). The marketed product melts trie 190-

,eight

191 ° C. And elemental analysis shows that the product is pure. This is proved by identical spectra of proton-magnetic resonance.

Found,%: C 49.7; H 6.5; N 17.7. Calculated,%: C 49.9; H 6.5; N 17.9. EXAMPLE 6 1,3-Bis- (5, 5-dimethyl 11 -hydantoyl-3) -cropan-2-ol. Analogously to Example 5, a dark yellow raw product is obtained from which 2307 g is isolated. It melts at 149-152 ° C. Elemental analysis shows that there is still 5.3% inorganic product. Thus, the yield of organic matter is

2185 g (100% of the calculated); according to elementary analysis, it consists of about 95% of the desired product.

To remove inorganic materials and colored by-products, the raw product is finely ground in a hammering knife and at room temperature and displaced from 1725 ml of denonized water until a homogeneous mass is obtained. After an hour-free unmixing, the mass is filtered on suction and

quickly sucked dry. A colorless precipitate is obtained, which is crushed and dried for 24 hours at and 30 torr. A purified product is obtained, yield 71% (1520 g). The product melts at 181 - 183 ° C. The inorganic product contains

0.9%. For the glycidylation reaction,

Note cleaned according to Example 5

product.

Example 7. 1,3-Bis- (5-methyl-5-ethylhydantonyl-3) -nronan-2-ol.

Similarly, in example 5, 148.3 g of 98.5% 5-methyl-5-ethylhydantoin (1.80 mol) containing 4% sodium chloride are reacted with 46.25 g of hydrochloride.

(0.5. Mol) in 500 ml of Mede dimethyl form in the interaction with 71.2 potassium carbonate (0.515 mol).

The reaction process and processing of the reaction mixture is carried out using Example 5. 172.9 g of product is obtained (calculated 170.2 g), which is contaminated with approximately 1.6% of dimethylformamide. This raw product is further processed. The proton magnetic resonance spectrum (60 MS H-NMR) shows the trace of dimethyl formamide (6 2.9 a 3.0) and 119 lnch; 11e of the desired molecule with signals iipii 6 0.8-1.05 (multi-year), 45 ( singlet), 55-2.0 (multi-year), 6 3.5-3.7 (multi-year),, 0-4.2 (multi-year), and

6 5.5-6.2 (multi-ticket).

Example 8. 1,3-Bis- (5- | 30nepropylantoinil-3) -pronan-2-ol.

As indicated in Example 5, 142.2 g of 5-isoyroyl hydantoin are reacted.

(1 mol), 46,25 g of epichlorgindrin (0.5 mol), 71.2 g of potassium carbonate (0.515 mol) and 0.4 g of potassium chloride in 500 ml of dimethylformamide. The processing of the raw product, which does not require further purification, is also carried out

according to Example 5. 171.8 g of a clear golden yellow glassy product (170.2 g are calculated) are obtained, which is still contaminated with about 1% dimethylformamide. The proton magnet resonance spectrum shows the following snaps; 6 0.8-1.2 (tie), 6 2.0-2.3 (multiple), 6 6-6.3 (multiplet), which corresponds to the structure to be lived.

Prpmer 9. 1,3-Bns- (5, 3-nenametledlengndantonyl-3) -nronan-2-ol.

According to the prnumer 5, 92.5 g of epichlorohydrate (1 mol) and 336.4 g of 5.5-nantamellengantonn (2 mol) in 900 ml of dnmethylformamnda prn nrnbavlenlen 142.3 g of calcium carbonate and 0.8 g of potassium chloride are condensed. The processing is carried out as indicated in procedure 5. Obtain 409.9 g of the desired bisgndantone (deducted blindly 392.4 g), containing about 5% more dnmetnlampamp, in the yellow crystal powder. For purification, the compound is recrystallized by a mixture of dpoxane and water (2: 1) in a ratio of 1: 3.5.

This gives 314.5 g (80.2% of the clarified) colorless powdery crystalline crystal, which is melted at 247.1 ° C (AAettler FP 51.1 ° / mission).

Found,%: C 57.9; II 7.3.

Calculated,%: C 58.1; H 7.2.

The mass spectrum corresponds to the expected structure: the molecular ion has an atomic mass of 392 mass units (M — 392.4% calculated), and fragmentation correspond. The спектр spectrum of iroton magnetic resonance shows the expected structure (60 MS I-NMR).

Example 10. 1,3-Bis- (5,5-tetramethylahydantoinyl-3) -propan-2-ol.

According to example 5, 154.2 g of 5,5-tetramethylene hydantoin (1 mol), 46.25 g of epichlorohydrin (0.5 mol) are reacted. 71.2 g of potassium carbonate (0.515 mol) and 0.4 g

. Calcium chloride and 500 ml of dimethylformamide. Recycle and isolate the desired bishydantopic, as indicated in measure 5. The raw material and recrystallize further from 360 ml of dnoxane and water (2: 1).

98 g (54% of the calculated, without revitalization of the uterine solution) of a colorless fine crystallization product, which melts at 185.2 ° C (Mettler FP 51.27 min), are obtained. The spectrum of proton magnetic resonance proves the structure expected.

PRIORITY AND RESPONSIBILITY

The method of obtaining double heterocyclic alcohols of the formula

.0

0

.x

to

X-С

III11

N N-CH-C-CH. -N NH

V / t, /

VT o

C II

HE

ABOUT

where X is a divalent alkylene group,

An R-hydrogen or an alkyl group of 1 to 4 carbon atoms, characterized in that a compound of the formula

x, 0

H /

m ij

interacts with 1,3-dichloropan-2-ol, having in group 2 position R, where R is hydrogen or an alkyl group containing 1-4 carbon atoms, or with ephalohydrin in the presence of relative hydrogen or hydrogen halide with the release of the target product with known accept