JPS59122441A - Novel 1-bromoethylethylcarbonate compound and manufacture - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention]

The present invention relates to a new compound 1-bromoethylethyl carbonate, known under the name α-bromodiethyl carbonate. Similar l-chloroethyl ethyl carbonate is a known compound, for example α-aminobenzene has the general formula (wherein R is an aliphatic or aromatic residue, an amino group, a substituted amino group or an amine group). A compound represented by a vine group and RIl represents hydrogen or a cation is reacted with 1-chloroethyl ethyl carbonate, and if necessary, the resulting varnish is further reacted to convert the A group into a free amino group. The conversion to obtain esters of the α-amine penicillin series having the general formula: is described. Absorption of this ester from the intestinal tract is superior to absorption of the free acid. This is because, upon oral administration, higher blood concentrations are obtained with the esters than with the corresponding free acid alpha-aminopenicillins. Regarding the above esterification reaction, the above British Patent Nos. 11 and 8
No. 68.506, which includes the formula: One group of compounds, iEH, in which R represents an alkyl group having 1 to 4 carbon atoms and R5 represents H, GH8 or 02H6) is included. By substituting R4, R5 and X,
Among others, 1-bromoethyl ethyl carbonate can be derived, but this compound is not described. U.S. Pat. No. 4,072,677 describes the compound R2X (where X is particularly bromine or iodine).
A group of rogens and R denoting in particular the ethoxycarbonyl oxydiethyl (i.e. 1-dithylethyl carbonate) group is mentioned, in which case the substitution results in inter alia 1-bromoethyl ethyl carbonate. The power you get! , but this compound is also not described. Similar 1-chloroethyl ethyl carbonate salts ethyl chloroformate, in direct sunlight. 1 was first prepared by Miiller by hydrogenation, and this product α-chloroethyl chloroformate was reacted with ethanol as shown in the following reaction equation (11. Muiller, rAnn, J 12,
50-(1889)): CI! Attempts have been made to prepare the corresponding bromo compounds without success. Direct bromination of diethyl carbonate was attempted by Messrs. Landenburg and Wichelhaus (rAnn, J..., 1° 168 (1869)).
). However, the reaction degrades diethyl carbonate to ethyl bromide, promal and carbon dioxide.
radiation) occurred. Nesmejanau et al. reported on "the effect of bromine on alkyl chlorocarbonates." . '(Eng.St, AKad, Nauk, 5SSR,
0tdel, khim, Nauk '681 (1
940) ). The reaction is reduced, with the production of 1,2-dibromoethane in particular. It is known that the 0-Br bond is less stable than the c-(3/ bond and that, as a result, 1-chloroethyl ethyl carbonate is less reactive in many reactions than the corresponding bromo compound; 1-bromoethyl ethyl carbonate. For this purpose, 1-chloroethyl
The rate of esterification with ethyl carbonate is slow;
As much as an equivalent amount of the 11-chloride compound is required to complete the esterification. Furthermore, long reaction times,
It requires harsh conditions such as high temperatures and the use of catalysts such as phase transfer catalysts. This harsh condition can be applied to varnishes containing sensitive compounds such as α-amine penicillin compounds.
In chilling applications, this compound results in partial degradation of sensitive β-lactam systems. This can be explained by the relatively low overall yield when 1111-chloroethyl ethyl carbonate is used for the esterification of ampicillin. Additionally, many chlorocompounds, including 1-chloroethyl ethyl carbonate 1, are known as lacrimal agents and skin irritants. For these reasons, any ester produced with 1-chloroethyl ethyl carbonate as the esterifying agent will contain trace amounts of 1-chloroethyl ethyl carbonate.
It is necessary to carry out an expensive complete purification operation to remove the ethyl carbonate. As mentioned above, the 0-Br bond is relatively unstable compared to the a-cl bond, so the esterification reaction requires a small amount of reagents, short reaction time, low reaction temperature, and no catalyst. It is expected that the reaction will proceed more slowly with 1-chloroethyl ethyl carbonate than with bromoethyl ethyl carbonate. When the acid to be esterified is sensitive, such as α-aminobenicillin type acid, the reaction time is shortened,
And low reaction temperatures are preferred to obtain the desired final product with minimal degradation of sensitive β-lactam moieties ((lactam moiety) C7). Therefore, in view of the various drawbacks of 1-chloroethyl ethyl carbonate □, it has long been desired to replace 1-chloroethyl ethyl carbonate with 1-bromoethyl ethyl carbonate, and the present invention first addresses this desire. It is to satisfy the following. In contrast, direct bromination of diethyl carbonate, ethyl chloroformate or ethyl bromoformate
The α-position to be brominated is o-co-. This is thought to be the reason for the failure of attempts to produce 1-bromoethyl ethyl carbonate, as it is severely inactivated by the adjacent electrons that remove the group. In the present invention, 1-propylene and lomoethyl ethyl carbonate can be easily produced with good yield by the following two methods. We have found that: a) in a free-radical type reaction, carried out with one compound of the group diethyl carbonate, ethyl chloroformate and ethyl bromoformate, starting from ethyl chloroformate or ethyl bromoformate; When used as a material, the brominating agent is present in an amount not exceeding the stoichiometric amount. [Product] -Promoethyl chloroformate and 1-bromoethyl bromoformate are new compounds, and these compounds are subjected to an ethanolate reaction to obtain 1-bromoethyl ethyl carbonate. b) In a fl exchange type reaction, chlorine in 1-chloroethylethyl carbonate is replaced by bromine by an excess amount of bromide salt. In the above free radical-type reactions, free radical initiation is carried out optionally with mild heating and with radical initiator compounds, such as UV and visible light, or with radical initiator compounds such as organic peroxides such as benzoyl peroxide, azobisisobutyl This can be done with lonitrile or other known free radical initiators. Free radical type bromination reactions are performed with elemental bromine or with e.g.
．． 8-dibromo-5,5-dimethyl-oxazolidine-
This can be done with a brominating agent such as 2,4-dione. The chlorine-bromine substitution reaction is carried out in an organic aprotio polar solvent such as, for example, acetone. The various methods of producing 1-bromoethyl ethyl carbonate in the present invention are shown in the following reaction scheme: r In the above reaction scheme, reactions (:) to (1v) are free radical method 1 and reaction (V) is chlorine - It is an odor-cumulative replacement method. The -bromoethyl chloroformate and l-bromoethyl bromoformate obtained in reaction (Iv) above are new compounds and form part of the present invention. (15) The various methods described above for producing 1-bromoethyl ethyl carbonate in the present invention are described: Reaction) The exact wavelength of light used to irradiate the reaction mixture is not critical. a few radiation sources emitting UV and visible light;
For example, regular tungsten lamps, quartz-iodine lamps and high pressure mercury lamps can be used, in all cases reacting with diethyl carbonate in the desired manner to produce bromine. The 0 irradiation efficiency, which is carefully measured with good results in the intense light of a high-pressure mercury lamp between 818 nm and 578 nm, is determined by the original absorption rate by bromine, independent of the wavelength of the irradiation. 1. The most effective light absorption is in the range 890-410 nm, but the bromination can be done at other wavelengths; the light needs to be absorbed by the bromine. Bromine of diethyl carbonate in the presence of light. The oxidation can be carried out at various temperatures. For example, the 'reaction can be carried out continuously from 60 to 126°C at the beginning and increased to elevated temperatures such as 140°C at the end of the reaction to produce good quality products in good yields. Since diethyl carbonate boils at 126° C., an upper limit is established for the reaction temperature unless high pressure equipment is used. At temperatures below 60°C, the reaction is extremely slow, and low-temperature reactions are inappropriate due to the time factor. In consideration of effective time and light efficiency, the preferred temperature is 80 to 1.126°C. The bromination reaction can be carried out in a hydroxyl group-free solvent that is inert to bromine and hydrogen bromide, such as carbon tetrachloride, dibromoethane, tetrachloroethane, chlorobenzene, and the like. A preferred 1-solvent is 1,1,2-trichlorotrifluoroethane (trade name [7 Leon 118J). If a solvent is used, bromine is preferably added slowly to a boiling solution of diethyl carbonate in the solvent. Typically, 1° of heat generated by the lamp is sufficient to boil the reaction mixture. The solvent ratio can vary over a wide range, for example in the case of carbon tetrachloride, from 0.4 to 4.2, preferably about 1.5. Preferably, free bromine is not present in the reaction mixture. For this purpose, bromine is preferably added in such a proportion that the solution is almost slightly colored by the addition of bromine. If the concentration of bromine is increased 7111, degradation of the reactants and reaction products occurs and the yield of 1-bromoethyl ethyl katobonate decreases significantly. However, the rate of bromine addition that maintains the color is influenced by system parameters such as lamp intensity, wavelength used, mixing efficiency, etc. If the total amount of bromine is less n K , the conversion of diethyl carbonate (1 is lower), although the vernier value is less. If excess bromine is used, bis-(l-bromoethyl) carbonate, such as The proportion of tribrominated products formed is increased. Considering the compromise between high conversion of starting materials and low yield of polybrominated products, the free N1 radical method in the present invention Then, add bromine below the theoretical t (stoichiometric amount).
It was found that it is necessary to add gold at an amount below 85% of the theoretical amount. In this dish, the polybrominated product can be less than 10 parts of the reaction product. 40 before theory
% bromine, polybromination can be ignored. Moreover, the above-mentioned reaction can be carried out without the presence of a solvent. In this case, diethyl carb 1. . The nate can be refluxed, irradiated, and bromine can be added gradually, so that the color of the reaction mixture changes from yellow to pale orange. When 40 parts of the stoichiometric amount of bromine is added, the reaction mixture consists mostly of diethyl carbonate and 1-proI moethyl carbonate, with negligible polybrominated by-products. Also, in this case more bromine can be added and a high conversion of diethyl carbonate can be achieved, but by-products begin to form. Alternatively, the free radical bromination of diethyl carbonate in the absence of a solvent can be carried out below the boiling point, e.g. 90°C, in which case the reaction proceeds very slowly, but the yield and quality of the product is It does not affect. In all the above-described cases of photoinduced free radical bromination of diethyl carbonate, heating and irradiation are continued until all bromine is consumed. The reaction mixture is then fractionally distilled under reduced pressure yielding 2 to 8 main fractions: solvent if present, unreacted diethylcado-bonate and finally alpha-bromodiethyl carbonate. (1) Any organic compound capable of forming free radicals by free radical initiated heating with an initiator compound using elemental bromine may be used, such as organic peroxides such as benzoyl peroxide and azobisisobutyronitrile. can. Reactions with free radical initiator compounds are carried out over the same ranges of temperature, concentrations of reactants, and concentrations of solvent, if present, as described above. A temperature of 85'°C can be used when the reaction is carried out in the dark with azobisisobutyronitrile as initiator;
Unlike the photobromination described in ), there is no need to significantly slow down the addition of bromine. In fact, bromine starts with a theoretical amount of 80
The additive can be added along with the free radical initiator and the reaction mixture is then heated. The remaining bromine is then added gradually when sufficient progress has been made. If a sufficient amount of initiator is present, the bromine is consumed and 1. This process results in good conversion of diethyl carbonate to 1-bromoethyl ethyl carbonate. However, with this method]
-Yield of bromoethyl ethyl carbonate is above

[1
) is better than the photochemical method described in 1.). (iii) Free radical bromination using a brominating agent (1) above
Bromination with elemental bromine described in (-) and (-) produces hydrogen bromide, which has a strong clotting effect on organic carbonates in addition to its environmental and hygienic protection. ,. For this purpose, it is preferable to use organic brominating agents which contain, for example, one odorant atom bonded to a nitrogen atom. This bromine is always liberated by free radical initiation and is available for bromination of other molecules. Such brominating agents include, for example, N-promosuccinimide, N-bromocaprolactam, N-bromoacetamide, 1,3-dibromo-5
, 5-dimethylimidazolidine-2,4-dione. Such a brominating agent is the starting compound described in (1) above.
It can replace elemental bromine in free radical brominations and free radical brominations using free initiating compounds described in (1) above. This method can be carried out with or without the presence of a solvent. In either case, it is preferred to use an 8-fold excess of diethyl carbonate per brominating agent, or in other words, to avoid the release of free bromine, the theoretical amount of brominating agent is about 83 to 35 times less. It is preferable to use (lv) Ethyl chloroformate or ethyl bromo 1 This method was followed unsuccessfully by Nesmejanau as described above. Despite this failure, the present invention confirmed that bromination proceeds slowly by maintaining the specific conditions required in the present invention. Bromination can be carried out by the methods described in (1) to (fill) above. The compound 1-bromoethyl chloroformate obtained in the intermediate step of this method is a novel compound 1L. 1-chloroethyl ethyl The carbonate is obtained commercially.The substitution reaction is carried out in a neutral polar solvent and the bromide source is a bromide salt such as lithium bromide or an organic Furthermore, the invention is not limited to the examples described above. The properties of the product 1-bromoethyl ethyl carbonate were investigated for the product of Example 1 described below. In Examples 2 to 7.11 and 12, the product is Example 1
The product was confirmed and evaluated. Next, the invention will be explained by way of example. Example 1 854 g (8 moles) of diethyl carbonate and qo
The mixture of ovt carbon tetrachloride was stirred and externally irradiated with a 1.5 KW iodine-quartz lung. Heat from the lamp was applied to the refluxing mixture. Then bromine (412,
8 g, 2.58 mol) was gradually added over a period of 15-17 hours through a dip tube protruding below the surface of the mixture. The color of the solution remained light red during the reaction. The temperature of the solution is 84
~85°C. During the addition, a large amount of hydrogen bromide was evolved. The reaction mixture was cooled, washed with aqueous sodium bisulfite solution, and dried over red sea bream sulfate. Carbon tetrachloride was distilled at normal pressure. The residue was fractionally distilled at 30 kg Hg pressure. The first fraction consisted of unreacted diethyl carbonate and the second fraction, boiling at 90..-95°0 (80 atm), was 1-1 bromoethyl ethyl carbonate. The pot residue was primarily bis-(l-bromoethyl) carbonate. The yield was approximately 52%, calculated on bromine. The physical data for 1-bromoethyl ethyl carbonate are as follows: Boiling point (60 HgJ 110℃ Bromine content 40.6 factor (theoretical value 40.61 factor) Density (D,) 1.4244 Refractive index (no)
1.4895 2.0 ppm 8H2M J=6H24,25pp
m 2H quadruple J = 7H26, 6 ppm IH quadruple J = 6 H2GO analysis was shown for the pure compound. Example 2 848.2 g (7.18 mol) of diethyl carbonate and 420 d of 1.1.2-)lichlorotri
,. A mixture of fluoroethane (9B6.9, 118J Freon) was stirred and irradiated with a 150W high pressure mercury immersion lamp. The mixture was heated with the lamp and began to boil quickly at 75°C. Bromine (9B6.9, 5. 85 mol) was added gradually throughout the dip tube at a rate such that the solution remained slightly colored.The addition was carried out over a period of 4/4 hour.During the addition:
The temperature inside the flask rose from 75°C to 94°C. H
Br was generated during the addition. The reaction was cooled to 40° C. and dry nitrogen was passed through until no more HBr fumes were generated. The reaction was then fractionally distilled as described above. The yield of isolated l-bromoethyl ethyl carbonate was 62%. Example 8 585 g of diethyl carbonate) (4.92 mol) l
was heated with an external 1500W iodine-quartz lamp. The mixture was brought to reflux (temperature: 115°C) by the heat generated by the Lang. 818.2 g (2.0 mol) of bromine was added. The color of the solution changed from yellow to pale orange. The temperature was lower than that at the beginning of the addition. ] 20"O, but rose again slowly by -3°. When all the bromine was consumed, the temperature reached 137°C.
Met. The reaction mixture was cooled and processed as described in Example 2. Fractional distillation was carried out to yield 68.5% l* of bromoethyl ethyl carbonate. The initial fraction contained more than about 6.5 tons of 1-bromoethyl ethyl carbonate. Example 4 69 (51,0 mmol) of diethyl carbonate,
A mixture of 100 d of carbon tetrachloride and 2817 (17.4 mmol) of bromine was refluxed in the dark, to which 1 g of azobisin butyronitrile was added and heated at the edge for 2 hours. Analysis of the product showed that 28% of the diethyl carbonate had been converted to 1-bromoethyl ethyl carbonate. Example 5 The procedure described in Example 4 was repeated, but using 0.1.9 azobisisobutyronitrile. After 2 hours, 6 loads of 1-bromoethyl ethyl carbonate were obtained. Furthermore,
0.1 g of azobisisoputiloni in the second part) IJ
When the mixture was further heated, the yield (27) increased to 9. Example 6 29.25.9 of diethyl carbonate and 5 g of 1
．． 8-dibromo-5,5-dimethylimidazolidine-2
,4-dione was heated to 95° C. and 0.5 g of azobisisobutyronitrile was added thereto. Solids quickly disappear and your friend. The reaction mixture was then heated to 110° C. for 1 hour. The reaction mixture was cooled and filtered. Pff
It was treated with an aqueous solution of t-sodium bisulfite and dried. G
C analysis confirmed that the diethyl carbonate of 51... was converted to 1-bromoethylethyl carbonate. The yield for 1,8-dibromo-5,6-dimethylimidazolidine-2,4-dione was 86% Example 7 195 fl of diethyl carbonate and 500 d of 1.1.2-1lichlorotri Fluoroethane mixture'
Illuminated externally with a 1.5 KW iodine-quartz lamp. The mixture is quickly heated by the heat generated from the rung. It refluxed to The temperature inside the flask was 60°C, 1°, and 79.0°! i'1,3-dibromo-5,Is
-dimethylimidazolidine-2,4-dione was added portionwise over 6 hours. The reaction mixture was irradiated and further
The mixture was refluxed for 0 minutes and cooled. Solid food was provided. The solution was fractionally distilled first at atmospheric pressure and then under vacuum. l-bromoethyl ethyl carbonate is 90”0
．． Distillation was carried out at 2 Or 1 mHg pressure to obtain 60 g of fraction, which was analyzed by Go and found to be 98% pure. Example 8 Ethyl chloroformate (271.6 g, 2.5 moles) was irradiated with an external 1.5 KW iodine-quartz lamp and purged with N2 throughout the reaction. While boiling, 1.0 mole of bromine was slowly added over t-10 hours. During this time the color of the solution was kept between yellow and light orange. The mixture was then fractionally distilled. ]-Bromoethyl chloroformate'i2011 was isolated in 60% yield in a fraction boiling at 50''O under Hg pressure.The chemical structure of this compound was determined by NMR.
(2.1 ppm double 8H, and 6.5 ppm quadruple IH). It was found to have a purity of 96% by 0.00 minute analysis. The compound was a colorless liquid with a pungent odor that gave off fumes in the air and decomposed easily when exposed to humid air. Example 9 32.57i of ethyl chloroformate and 0.5I
A mixture of azobisin butyronitrile was refluxed in the dark and 40.8.9 of bromine was slowly added over 1 hour. Two hours after the start of the addition, the reaction mixture was analyzed. The resulting complex mixture contained 11"' of ethyl chloroformate and 47" of 1-bromoethyl chloroformate. Example 10 10.89 of ethyl chloroformate, 5 (IL) of carbon tetrachloride , 18 g of N-promosuccinimide and 0.5 I of azobisisobutyronitrile to 80 g.
Refluxed for minutes. Analyze the product L, 8% 1-
It was confirmed that it contained bromoethyl chloroformate. Example 11 87.49 1-bromoethyl chloroformate, 20
f+7 dichloromethane and 26. ! A mixture of 9 and anhydrous sodium carbonate was stirred at room temperature. 12 to this mixture
9 m of absolute ethanol was added dropwise over 45 minutes, followed by the addition of 4 d of absolute ethanol after 2.8 and 4 hours, respectively. After 5 hours, the reaction mixture was filtered. Dichloromethane and excess ethanol were evaporated at room temperature. The residue was distilled in vacuo to obtain 28 g of 1-bromoethyl ethyl carbonate. Example] 2 1-chloroethyl ethyl carbonate of 15.259)
(0.1 mol), 84.8,! i+lithium bromide (
A mixture of 0.4 mol] and 200 mol of acetone was refluxed for 2 hours. The acetone was evaporated and the residue was stirred with 200 II/l dichloromethane. The solids were filtered and the dichloromethane was evaporated. The residual liquid was analyzed to contain 65 grams of 1-bromoethyl ethyl carbonate and 85 grams of 1-chloroethyl ethyl carbonate. This shows its use in the synthesis of biosynthetic penicillin. Synthetic 1-bromoethyl ethyl carbonate (145.8g
) in acetone ('120gn1).
Sodium bicarbonate (160 g) and Ambi 111 at °C
Cylindane potassium salt (ADS) (240g) was added. This suspension was heated at 40°C for 5 hours,
Then, all water (720+a/) was added, and ethyl acetate (720+a/) was added.
Stirring was continued for an additional hour when 0tu) was added. The organic phase was separated, washed with 20% aqueous sodium chloride solution (720 tt/) and then concentrated under reduced pressure (below 35°C) to a thick residue. This residue was mixed with acetone (720 tt/) and water (24 tt/).
yd) and further diluted with water (12d)...
A concentrated HOIC80d) solution was added dropwise. Next, Oi 7JO
HOI (1:1, 1.5yd) was added until the pH of the contents was approximately 2.2. Next, 40 g of magnesium sulfate C) was added to this mixture, stirred for 10 minutes, and filtered. Butyl acetate □(
4oo*) was added and evaporated in vacuo to remove acetone and butyl acetate (ca. 820 m/). The residue was diluted with butyl acetate (880m) and the solvent portion was evaporated under reduced pressure. Separate the solids from house to house and collect butyl acetate (120111/) and I
Wash with ethyl acetate (120 yd) and 40 °C in vacuo.
to obtain pure bacampicillin hydrochloride (1
76.2 g, yield 71.8 g). The analytical data showed a purity of 98.7%, all meeting U, S, A, and pharmacopeia requirements of 1. Production of phosphorus Acetone (24,4Ql/), Methyl acetoacetate?
11) (8,4!/) and triethylamine (9d)
The mixture was heated to 40"C, then ampicillin trihydrate (24.2g) was added and the mixture was heated for 5 hours. 1-Promoethylepatyl carbonate (17,'15 I, 20 g of sodium bicarbonate C) and acetone (48,4 g L) were then added to the reaction mixture and heated at 1140<0>C for 5 hours. Thereafter, deionized water (72,41a/)'Ik
Decompose excess BDEO by sprinkling it with TLO test.
The mixture was stirred until no 1.1BDEC remained. Next, 7111 L of ethyl acetate (72,4!/) was added to the reaction mixture, filtered, the organic phase was washed with 20% sodium chloride solution (71a/), and a 1:1 H01 solution was added dropwise to give about 1 A final stable pH of 2.21. was obtained which was maintained for .5 hours. Butyl acetate (75m) was added to this solution and the
It was condensed to dryness at 0°C to 11, then added with an additional amount of butyl acetate (7
5m)k was added and a fraction of 5-1Od was distilled off under the same conditions. 2. Filter solids,
Butyl acetate (10!/) and ethyl acetate (20tt)
/) and dried in a vacuum oven at 40°C. Bacampicillin HOI 19.75 g (65%)
It had a purity of 95.6% and also had U, S, A, and pharmacopeia requirements. A mixture of potassium benzyl penicillin (20 g), 1-1" promoethyl carbonate (19,15 g), sodium bicarbonate (18,15,9), tetrabutylammonium bromide (1 g) and acetone (60 trd) Water (60 tt/) was added to the reaction mixture and the reaction mixture was heated for 1 hour at Kl.
The mixture was stirred and then ethyl acetate (BOd) was added. Separate the organic phase and dilute with bicarbonate) IJum solution (2X6
0 m'L/) and 20% sodium chloride solution. Dry the organic phase over sodium sulfate and remove with charcoal!・・・(
35) Color and evaporate the solvent under reduced pressure to remove GO and mercury(1)1
1-Ethoxycarbonyloxyethyl benzyl penic acid (17) with 99% purity by titration 22.1.9
was obtained (total yield 91.1%). Patent applicant Orbet B.V.

Claims (1)

[Scope of Claims] A 1-bromoethyl ethyl carbonate compound represented by the general formula % (in the formula, Xl'XC1, Br or U-00H2CH8). 2. The 1-bromoethyl ethyl carbonate compound according to claim 1, wherein the compound is 1-bromoethyl ethyl carbonate. & The 1-bromoethyl ethyl carbonate compound according to claim 1, wherein the compound is 1-bromoethyl chloroformate. 1-bromoethyl ethyl carbonate compound according to claim 1, wherein the compound is 1-bromoethyl bromoformate. , '...6 1-bromoethyl et dol carbonate compound represented by the general formula % formula % (wherein X represents C/, Br or -00)120H8), bromination of a compound represented by (with the same meaning as above) under conditions conducive to free radical formation, and the amount of bromine used for this bromination is less than the stoichiometric amount; A method for producing a 1-bromoethyl ethyl carbonate compound as a percentage. The method for producing a 1-bromoethyl ethyl carbonate compound according to claim 5, wherein the bromination is carried out by irradiation. 1 of item 6 of the special request for bromination heating
- Bromoethyl ethyl carbonation... - Method for producing hardware. & A method for producing and using a 1-bromoethyl ethyl carbonate compound according to claim 5, wherein the bromination is carried out by heating in the presence of at least one organic compound which forms free radicals upon heating. 9. A method for producing a 1-bromoethyl ethyl carbonate compound according to any one of claims 9 to 1-bromoethyl ethyl carbonate according to claim 8, in which the organic compound is a peroxide or azobisisobutyronitrile. . 11. A method for producing a 1,1-bromoethyl ethyl carbonate compound according to any one of claims 5 to 9, in which an organic brominating agent is used for bromination. X! The brominating agents were N-promosuccinido, N-promocaglolactam, N-bromoacetamide and 1
．． 8-dibromo-5,5-dimethy2. . 1 of the group of limidazolidi7'-2,4-diones
A method for producing a 1-bromoethyl ethyl carbonate compound according to claim 11 as a seed. 1 & 1-bromoethyl according to any one of claims 5 to 12, wherein the starting material having the general formula of claim 5 is dissolved in an inert bath agent having no hydroxyl group. Method for producing ethyl carbonate compound. 14L Solvent: carbon tetrachloride, dibromoethane, chlorine 1
Parobenzene, tetrachloroethane and 1°1,2-
) A method for producing a 1-bromoethyl ethyl carbonate compound according to claim 1B, wherein the 1-bromoethyl ethyl carbonate compound is one of the group of dichlorotrifluoroethane. 1 & Claims 5 to 1 in which the starting material having the general formula of Claim 5 is brominated without using a solvent.
A method for producing a 1-bromoethyl ethyl carbonate compound according to any one of Item 2.
...1a The method for producing a 1-bromoethyl ethyl carbonate compound according to claim 11', wherein the solvent is acetone. 1'1. A method for producing a 1-bromoethyl ethyl carbonate compound according to any one of claims 5 to 16, wherein the starting material is diethyl carbonate. 1 & Obtaining l-bromoethyl chloroformate using ethyl chloroformate as a starting material Claim 1
A method for producing the 1-promoethyl ethyl carbonate compound described in Section 1. 19. 1 using ethyl bromoformate as the starting material
- A method for creating a 1-bromoethylethyl carbonate compound according to claim 1 to obtain promoethyl bromoformate. 2o, l-Furomoethyl chloroforme-1ti is a method for producing a 1-bromoethyl ethyl carbonate compound according to claim 1, wherein l-bromoethyl bromoformate is reacted with ethanol. 2. A process for producing a 1-bromoethyl ethyl carbonate compound according to claim 1, wherein 1-chloroethyl ethyl carbonate is reacted with an excess of bromide salt in an organic neutral polar solvent. Claim 2 in which the bromide salt is lithium bromide
A method for producing a 1-bromoethyl ethyl carbonate compound according to item 1. 2 & 1-bromoethyl chloride according to claim 21, wherein the bromide salt is quaternary ammonium bromide. A method for producing an ethyl carbonate compound. 29. The method for producing a 1-bromoethyl ethyl carbonate compound according to claim 28, wherein the interstitial ammonium chloride is tetrabutylammonium bromide.