JPH04273850A - Production of symmetric type 1,3-disubstituted urea - Google Patents
Production of symmetric type 1,3-disubstituted ureaInfo
- Publication number
- JPH04273850A JPH04273850A JP3580891A JP3580891A JPH04273850A JP H04273850 A JPH04273850 A JP H04273850A JP 3580891 A JP3580891 A JP 3580891A JP 3580891 A JP3580891 A JP 3580891A JP H04273850 A JPH04273850 A JP H04273850A
- Authority
- JP
- Japan
- Prior art keywords
- reaction
- disubstituted urea
- phosgene
- primary amine
- symmetric type
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 12
- -1 1,3-disubstituted urea Chemical class 0.000 title abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical group ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 claims abstract description 3
- 150000003672 ureas Chemical class 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 claims 1
- 150000003141 primary amines Chemical class 0.000 abstract description 15
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 abstract description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 11
- 238000000034 method Methods 0.000 abstract description 10
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 abstract description 6
- 150000007529 inorganic bases Chemical class 0.000 abstract description 6
- ZWAVGZYKJNOTPX-UHFFFAOYSA-N 1,3-diethylurea Chemical compound CCNC(=O)NCC ZWAVGZYKJNOTPX-UHFFFAOYSA-N 0.000 abstract 1
- 239000003513 alkali Substances 0.000 abstract 1
- 150000007530 organic bases Chemical class 0.000 abstract 1
- 239000002904 solvent Substances 0.000 abstract 1
- 238000006467 substitution reaction Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 6
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 6
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 235000013877 carbamide Nutrition 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- OHJMTUPIZMNBFR-UHFFFAOYSA-N biuret Chemical compound NC(=O)NC(N)=O OHJMTUPIZMNBFR-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N 1,3-di(propan-2-yl)urea Chemical compound CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 2
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- BHRZNVHARXXAHW-UHFFFAOYSA-N sec-butylamine Chemical compound CCC(C)N BHRZNVHARXXAHW-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- 229940057054 1,3-dimethylurea Drugs 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- MGJKQDOBUOMPEZ-UHFFFAOYSA-N N,N'-dimethylurea Chemical compound CNC(=O)NC MGJKQDOBUOMPEZ-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- CNWSQCLBDWYLAN-UHFFFAOYSA-N butylurea Chemical compound CCCCNC(N)=O CNWSQCLBDWYLAN-UHFFFAOYSA-N 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【0001】0001
【産業上の利用分野】本発明は第1級アミン類から医薬
、農薬等の原料化合物として有用な対称型の1,3−ジ
置換尿素を製造する方法に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing symmetrical 1,3-disubstituted ureas useful as raw material compounds for pharmaceuticals, agricultural chemicals, etc. from primary amines.
【0002】0002
【従来の技術】低級アルキル基による対称型の1,3−
ジ置換尿素を製造する方法としては、下記の方法が知ら
れている。
(1)尿素と第1級アミンとの交換反応により製造する
方法(特公平2−7945号)
(2)炭酸エステルと第1級アミンとの交換反応により
製造する方法(特公昭62−17572号)(3)二酸
化炭素と第1級アミンを高温高圧下に反応させ製造する
方法(特公昭62−9107 号)(4)白金系触媒存
在下に第1級アミンと一酸化炭素を反応させて製造する
方法(特開昭60−163853 号)(5)無機塩基
の存在下に、第1級アミンとホスゲンを反応させて対称
型の1,3−ジ置換尿素を合成する方法(Chemic
al Reviews, 73, No.1, 75
(1973) )[Prior art] Symmetrical 1,3- by lower alkyl group
The following methods are known as methods for producing di-substituted ureas. (1) A method for producing by an exchange reaction between urea and a primary amine (Japanese Patent Publication No. 2-7945) (2) A method for producing by an exchange reaction between a carbonate ester and a primary amine (Japanese Patent Publication No. 17572/1982) ) (3) A method of manufacturing by reacting carbon dioxide and a primary amine under high temperature and high pressure (Japanese Patent Publication No. 1987-9107) (4) Reacting a primary amine with carbon monoxide in the presence of a platinum catalyst. A method for producing symmetrical 1,3-disubstituted urea by reacting a primary amine with phosgene in the presence of an inorganic base (Chemical
al Reviews, 73, No. 1, 75
(1973) )
【0003】0003
【本発明が解決しようとする課題】しかしながら、上記
の(1)〜(4)の方法は、いづれも200℃前後の高
温で、15〜50バールという高圧下に反応を行ってい
る。また、多くの場合に第1級アミン類を大過剰に用い
ているために、その分離、回収が必要である。さらに、
上記の理由から製造設備も大型で複雑なものとなる等の
工業的に製造を行う上で好ましくない。[Problems to be Solved by the Invention] However, the above methods (1) to (4) all carry out the reaction at a high temperature of around 200° C. and under a high pressure of 15 to 50 bar. Furthermore, since primary amines are used in large excess in many cases, it is necessary to separate and recover them. moreover,
For the above reasons, the manufacturing equipment becomes large and complicated, which is not preferable for industrial manufacturing.
【0004】また上記(5)の方法を低級アルキル基置
換の第1級アミンに適応して1,3−ジ置換尿素を製造
する方法についてはこれまで報告されていない。これは
低級のモノアルキルアミンを使用した場合には、通常の
条件下ではビウレットやグアニジン等の不純物を生成し
易いため、収率良く、高純度の1,3−ジ置換尿素を得
るのが困難なためと考えられる。[0004] Furthermore, there has been no report on a method for producing 1,3-disubstituted urea by applying the method (5) above to a primary amine substituted with a lower alkyl group. This is because when lower monoalkylamines are used, impurities such as biuret and guanidine are likely to be produced under normal conditions, making it difficult to obtain high-yield, high-purity 1,3-disubstituted urea. This is thought to be for a reason.
【0005】かかる事情に鑑み、本発明者らは低級アル
キル基置換の第1級アミンとホスゲンを反応させ対称型
の1,3−ジ置換尿素を製造する方法について鋭意検討
した結果、水溶媒中で無機塩基を添加しながら反応液の
pHを9〜14に保持しながらホスゲンを反応させるこ
とにより、常温で、高収率で1,3−ジ置換尿素を製造
できることを見出し、本発明を完成させるに至った。In view of the above circumstances, the present inventors conducted intensive studies on a method for producing symmetrical 1,3-disubstituted urea by reacting a lower alkyl group-substituted primary amine with phosgene. discovered that 1,3-disubstituted urea could be produced in high yield at room temperature by reacting phosgene while maintaining the pH of the reaction solution at 9 to 14 while adding an inorganic base, and completed the present invention. I ended up letting it happen.
【0006】[0006]
【問題を解決するための手段】すなわち、本発明は一般
式、RNH2 (式中、Rは1〜4個の炭素原子よりな
る非分枝鎖または分枝鎖のアルキル基を表す)で示され
る第1級アミンとホスゲンとを無機塩基を添加しながら
反応液のpHを8〜14の範囲に保持しつつ反応させる
ことを特徴とする一般式、RNHCONHR(式中、R
は前記と同じ)で示される対称型の1,3−ジ置換尿素
の製造法である。Means for Solving the Problems The present invention is represented by the general formula RNH2, where R represents an unbranched or branched alkyl group of 1 to 4 carbon atoms. RNHCONHR (in the formula, R
is the same as above).
【0007】本発明で用いられる第1級アミンとしては
、例えばメチルアミン、エチルアミン、n−プロピルア
ミン、イソプロピルアミン、シクロプロピルアミン、n
−ブチルアミン、イソブチルアミン、第2級ブチルアミ
ン、第3級ブチルアミン、シクロブチルアミン等が挙げ
られる。Examples of the primary amine used in the present invention include methylamine, ethylamine, n-propylamine, isopropylamine, cyclopropylamine, n-propylamine, and n-propylamine.
-butylamine, isobutylamine, secondary butylamine, tertiary butylamine, cyclobutylamine and the like.
【0008】本反応は水の存在下に実施されるが、水と
有機溶媒の混合溶媒系でも実施できる。かかる有機溶媒
としてはヘキサン、ヘプタン、シクロヘキサン等の炭化
水素類、ベンゼン、トルエン、クロルベンゼン等の芳香
族炭化水素類、ジエチルエーテル、ジブチルエーテル、
テトラヒドロフラン等のエーテル類、酢酸エチル、酢酸
ブチル等のエステル類、塩化メチレン、クロロホルム、
1,2−ジクロロエタン等の低級ハロゲン化炭化水素類
等が用いられる。Although this reaction is carried out in the presence of water, it can also be carried out in a mixed solvent system of water and an organic solvent. Such organic solvents include hydrocarbons such as hexane, heptane, and cyclohexane, aromatic hydrocarbons such as benzene, toluene, and chlorobenzene, diethyl ether, dibutyl ether,
Ethers such as tetrahydrofuran, esters such as ethyl acetate and butyl acetate, methylene chloride, chloroform,
Lower halogenated hydrocarbons such as 1,2-dichloroethane are used.
【0009】ホスゲンの使用量は第1級アミン1モル当
り約0.3〜0.6モル使用すれば良く、好ましくは約
0.4〜0.5モルの範囲である。ホスゲンの使用量が
少ないと第1級アミンが多く残存し、収率が低下する。
また、ホスゲンの使用量が多すぎてもビウレット等の副
生物が多くなるので望ましくない。The amount of phosgene used may be about 0.3 to 0.6 mol, preferably about 0.4 to 0.5 mol, per mol of primary amine. If the amount of phosgene used is small, a large amount of primary amine remains and the yield decreases. Furthermore, if the amount of phosgene used is too large, it is also undesirable because by-products such as biuret will increase.
【0010】無機塩基としては水酸化リチウム、水酸化
ナトリウム、水酸化カリウム、水酸化カルシウム、炭酸
ナトリウム、炭酸カリウム等が挙げられる。水に対する
溶解度が大きいこと、及びホスゲンとの反応で副成する
無機塩の水に対する溶解度が大きいことから、好ましく
は水酸化ナトリウムが用いられる。[0010] Examples of the inorganic base include lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, and the like. Sodium hydroxide is preferably used because it has a high solubility in water and because an inorganic salt formed as a by-product in the reaction with phosgene has a high solubility in water.
【0011】無機塩基は反応中に、反応液のpHが約8
〜14、好ましくは約9〜13の範囲に保持されるよう
に添加される。pHが約8以下の場合には、尿素生成反
応が抑制されたり、グアニジン等の不純物が生成するた
め好ましくない。またpHが14を越える高アルカリ濃
度の条件で反応を行うと、ホスゲンの分解が多くなった
り、ビウレット等の不純物が生成するため好ましくない
。[0011] The inorganic base is used during the reaction when the pH of the reaction solution is about 8.
-14, preferably about 9-13. If the pH is about 8 or less, the urea production reaction is inhibited or impurities such as guanidine are produced, which is not preferable. Furthermore, if the reaction is carried out under conditions of a high alkaline concentration with a pH exceeding 14, it is not preferable because phosgene decomposition increases and impurities such as biuret are produced.
【0012】反応は一般には約0℃〜70℃、好ましく
は約10℃〜50℃の温度で実施される。この温度で反
応は充分速く進む。反応熱の除去を行いながらこの温度
範囲を維持して反応を行う。反応温度が約70℃を越す
と、ホスゲンの加水分解が顕著になり、また約0℃より
低くなると反応が遅くなり好ましくない。The reaction is generally carried out at a temperature of about 0°C to 70°C, preferably about 10°C to 50°C. At this temperature the reaction proceeds sufficiently fast. The reaction is carried out while maintaining this temperature range while removing the reaction heat. When the reaction temperature exceeds about 70°C, hydrolysis of phosgene becomes significant, and when the reaction temperature falls below about 0°C, the reaction slows down, which is not preferable.
【0013】反応圧力は、加圧でも減圧でも別段差支え
ないが通常、常圧で実施される。反応方法は連続式、半
連続式、または回分式のいづれでも行うことができる。
反応は通常、第1級アミン類と水、または場合により有
機溶媒をあらかじめ混合した溶液中にホスゲンと無機塩
基の水溶液とを反応液のpHが8〜14に保持されるよ
うに導入して行われる。The reaction pressure may be either increased or reduced pressure, but the reaction is usually carried out at normal pressure. The reaction method can be carried out continuously, semi-continuously, or batchwise. The reaction is usually carried out by introducing an aqueous solution of phosgene and an inorganic base into a premixed solution of primary amines and water, or in some cases an organic solvent, such that the pH of the reaction solution is maintained at 8 to 14. be exposed.
【0014】上記反応で生成した1,3−ジ置換尿素は
反応液中に既に結晶として析出しているか、または反応
液を冷却することで結晶として析出する。常法によりこ
れをろ過し、乾燥することで目的の生成物が単離される
。この生成物は必要に応じて再結晶等の手段によりさら
に精製される。The 1,3-disubstituted urea produced in the above reaction is already precipitated as crystals in the reaction solution, or is precipitated as crystals by cooling the reaction solution. The desired product is isolated by filtering and drying in a conventional manner. This product is further purified by means such as recrystallization, if necessary.
【0015】[0015]
【発明の効果】本発明の方法により、対称型の1,3−
ジ置換尿素を温和な条件下に容易にかつ収率良く製造す
ることができる。Effect of the invention: By the method of the present invention, symmetrical 1,3-
Disubstituted urea can be easily produced under mild conditions with good yield.
【0016】[0016]
【実施例】以下、本発明を実施例により更に具体的に説
明するが、本発明はこれらの実施例に限定されるもので
はない。EXAMPLES The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited to these Examples.
【0017】実施例1
ガス導入管、還流冷却器、温度計、攪拌器、滴下ロート
、pH電極を備えたガラス製反応器に、エチルアミンの
70%水溶液64.4g(1.00モル)、水26.0
gを仕込み、攪拌下にホスゲン44.5g(0.45モ
ル)と23%カセイソーダ水溶液191g(1.10モ
ル)を温度10〜20℃、pH10〜13に調整しつつ
3時間にわたって導入した。Example 1 64.4 g (1.00 mol) of a 70% aqueous solution of ethylamine and water were placed in a glass reactor equipped with a gas inlet tube, reflux condenser, thermometer, stirrer, dropping funnel, and pH electrode. 26.0
44.5 g (0.45 mol) of phosgene and 191 g (1.10 mol) of a 23% caustic soda aqueous solution were introduced over 3 hours while adjusting the temperature to 10-20° C. and pH 10-13 while stirring.
【0018】導入終了後、反応液を5℃まで冷却すると
生成物の結晶が析出してスラリー状となったので、これ
をろ過し、冷水15gで洗浄した後、減圧下に乾燥して
1,3−ジエチル尿素93.6gを得た。収率は81%
であり、純度は97%であった。また、融点は108〜
109℃であった。After the introduction, when the reaction solution was cooled to 5° C., crystals of the product were precipitated to form a slurry, which was filtered, washed with 15 g of cold water, and dried under reduced pressure. 93.6 g of 3-diethylurea was obtained. Yield is 81%
The purity was 97%. Also, the melting point is 108~
The temperature was 109°C.
【0019】実施例2
エチルアミンの代わりに、メチルアミンの40%水溶液
77.7g(1.00モル)を用いた以外は実施例1と
同様に行った。生成物である1,3−ジメチル尿素を6
4.1g得た。収率は73%であり、純度は98%であ
った。また融点は102〜104℃であった。Example 2 The same procedure as in Example 1 was carried out except that 77.7 g (1.00 mol) of a 40% aqueous solution of methylamine was used instead of ethylamine. The product 1,3-dimethylurea is
4.1g was obtained. The yield was 73% and the purity was 98%. Moreover, the melting point was 102-104°C.
【0020】実施例3
エチルアミンの代わりにイソプロピルアミンを59.1
g(1.00モル)、また水を45gを仕込んだ以外は
実施例1と同様に行った。生成物である1,3−ジイソ
プロピル尿素を123.8g得た。収率は86%であり
、純度は97%であった。また融点は188〜190℃
であった。Example 3 Isopropylamine was used instead of ethylamine at 59.1
The same procedure as in Example 1 was conducted except that 45 g (1.00 mol) and 45 g of water were added. 123.8 g of the product 1,3-diisopropylurea was obtained. The yield was 86% and the purity was 97%. Also, the melting point is 188-190℃
Met.
【0021】実施例4
エチルアミンの代わりに第2級ブチルアミン73.1g
(1.00モル)、また水を45gを仕込んだ以外は実
施例1と同様に行った。生成物である1,3−ジ−第2
級ブチル尿素を159.5g得た。収率は93%であり
、純度は96%であった。また融点は133−135℃
であった。Example 4 73.1 g of secondary butylamine instead of ethylamine
The same procedure as in Example 1 was conducted except that 45 g of water (1.00 mol) and 45 g of water were added. The product 1,3-di-second
159.5 g of grade butyl urea was obtained. The yield was 93% and the purity was 96%. Also, the melting point is 133-135℃
Met.
Claims (1)
の炭素原子よりなる非分枝鎖または分枝鎖のアルキル基
を表す)で示される第1級アミンとホスゲンとを無機塩
基を添加しながら反応液のpHを8〜14の範囲に保持
しつつ反応させることを特徴とする一般式、RNHCO
NHR(式中、Rは前記と同じ)で示される対称型の1
,3−ジ置換尿素の製造法。Claim 1: A primary amine represented by the general formula RNH2 (wherein R represents an unbranched or branched alkyl group having 1 to 4 carbon atoms) and phosgene are combined into an inorganic A general formula, RNHCO, characterized in that the reaction is carried out while maintaining the pH of the reaction solution in the range of 8 to 14 while adding a base.
Symmetrical 1 represented by NHR (wherein R is the same as above)
, 3-disubstituted urea production method.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP3035808A JP3021705B2 (en) | 1991-03-01 | 1991-03-01 | Process for producing symmetric 1,3-disubstituted ureas |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP3035808A JP3021705B2 (en) | 1991-03-01 | 1991-03-01 | Process for producing symmetric 1,3-disubstituted ureas |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH04273850A true JPH04273850A (en) | 1992-09-30 |
JP3021705B2 JP3021705B2 (en) | 2000-03-15 |
Family
ID=12452230
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP3035808A Expired - Fee Related JP3021705B2 (en) | 1991-03-01 | 1991-03-01 | Process for producing symmetric 1,3-disubstituted ureas |
Country Status (1)
Country | Link |
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JP (1) | JP3021705B2 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002520318A (en) * | 1998-07-08 | 2002-07-09 | ビーエーエスエフ アクチェンゲゼルシャフト | Method for producing carbonyldiimidazole |
CN103113265A (en) * | 2013-02-18 | 2013-05-22 | 辽宁大学 | Method for synthesizing symmetric urea compounds from nitrocompounds |
-
1991
- 1991-03-01 JP JP3035808A patent/JP3021705B2/en not_active Expired - Fee Related
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002520318A (en) * | 1998-07-08 | 2002-07-09 | ビーエーエスエフ アクチェンゲゼルシャフト | Method for producing carbonyldiimidazole |
CN103113265A (en) * | 2013-02-18 | 2013-05-22 | 辽宁大学 | Method for synthesizing symmetric urea compounds from nitrocompounds |
Also Published As
Publication number | Publication date |
---|---|
JP3021705B2 (en) | 2000-03-15 |
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