亞磷酸三(2-氯乙基)酯和NN-雙羥乙基苯胺的連續(xù)制備研究

碩士學(xué)位論文IV第一章緒論1.1研究背景環(huán)氧化合物[1-2]是化工工業(yè)中一類重要的生產(chǎn)原料ADDINEN.CITE<EndNote><Cite><Author>姚本鎮(zhèn)</Author><Year>2011</Year><RecNum>143</RecNum><DisplayText><styleface="superscript">[1]</style></DisplayText><record><rec-number>143</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586848854">143</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author><styleface="normal"font="default"charset="134"size="100%">李麗芳</style><styleface="normal"font="default"size="100%"></style><styleface="normal"font="default"charset="134"size="100%">姚本鎮(zhèn)</style></author></authors></contributors><titles><title><styleface="normal"font="default"charset="134"size="100%">環(huán)氧乙烷下游產(chǎn)品研究開發(fā)進(jìn)展</style></title><secondary-title><styleface="normal"font="default"size="100%"></style><styleface="normal"font="default"charset="134"size="100%">石油化工技術(shù)與經(jīng)濟(jì)</style></secondary-title></titles><pages>21-27</pages><volume>27</volume><number>06</number><dates><year>2011</year></dates><urls></urls></record></Cite></EndNote>[1]。由于其結(jié)構(gòu)的不穩(wěn)定性，分子內(nèi)部張力較大，分子內(nèi)的環(huán)氧結(jié)構(gòu)極易與許多含有活潑基團(tuán)的化合物進(jìn)行開環(huán)加成反應(yīng)，從而合成出眾多重要的化工產(chǎn)品ADDINEN.CITEADDINEN.CITE.DATA[2-4]。環(huán)氧化合物中環(huán)氧乙烷每年全球的消耗量為2400萬噸，被廣泛應(yīng)用醫(yī)藥、洗滌、電子、農(nóng)藥、紡織、造紙、汽車等方面，可以制造合成纖維、汽車防凍劑、增塑劑以及炸藥等一系列的化工產(chǎn)品。環(huán)氧乙烷與三氯化磷反應(yīng)生成的亞磷酸三(2-氯乙基)酯，是合成乙烯利ADDINEN.CITE<EndNote><Cite><Author>Steffens</Author><Year>2005</Year><RecNum>70</RecNum><DisplayText><styleface="superscript">[5]</style></DisplayText><record><rec-number>70</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586762371">70</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Steffens,C.A.</author><author>Giehl,R.F.H.</author><author>Brackmann,A.</author></authors></contributors><titles><title>'Gala'applestoredincontrolledatmosphereandtreatedwithaminoethoxyvinylglycineandethephon</title><secondary-title>PesquisaAgropecuariaBrasileira</secondary-title></titles><periodical><full-title>PesquisaAgropecuariaBrasileira</full-title></periodical><pages>837-843</pages><volume>40</volume><number>9</number><dates><year>2005</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0100-204X</isbn><accession-num>WOS:000233432900001</accession-num><urls><related-urls><url><GotoISI>://WOS:000233432900001</url></related-urls></urls><electronic-resource-num>10.1590/s0100-204x2005000900001</electronic-resource-num></record></Cite></EndNote>[5]和磷系阻燃劑的重要中間體。環(huán)氧乙烷與苯胺反應(yīng)生成的N，N-雙羥乙基苯胺是化工領(lǐng)域的一種重要有機(jī)中間體，被廣泛應(yīng)用于醫(yī)藥和染料行業(yè)ADDINEN.CITE<EndNote><Cite><Author>楊鳳玲</Author><Year>2000</Year><RecNum>144</RecNum><DisplayText><styleface="superscript">[6]</style></DisplayText><record><rec-number>144</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586849057">144</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author><styleface="normal"font="default"charset="134"size="100%">賈廷奎</style><styleface="normal"font="default"size="100%"></style><styleface="normal"font="default"charset="134"size="100%">李金成</style><styleface="normal"font="default"size="100%"></style><styleface="normal"font="default"charset="134"size="100%">師紅娟</style><styleface="normal"font="default"size="100%"></style><styleface="normal"font="default"charset="134"size="100%">楊鳳玲</style></author></authors></contributors><titles><title><styleface="normal"font="default"size="100%">N_N_</style><styleface="normal"font="default"charset="134"size="100%">雙羥乙基苯胺的合成及應(yīng)用</style></title><secondary-title>2000</secondary-title></titles><periodical><full-title>2000</full-title></periodical><pages>14-17</pages><volume>2</volume><number>04</number><dates><year>2000</year></dates><urls></urls></record></Cite></EndNote>[6]。這類反應(yīng)均為強(qiáng)放熱反應(yīng)，在釜式反應(yīng)中不但需要強(qiáng)烈的攪拌以防止體系局部過熱，還需要大量的冷卻循環(huán)介質(zhì)以及時(shí)移除體系中的熱量。此外，這類反應(yīng)在溫度過高時(shí)還容易引發(fā)一系列副反應(yīng)導(dǎo)致產(chǎn)品品質(zhì)降低。環(huán)氧乙烷是一種易燃物質(zhì)且強(qiáng)致癌的物質(zhì)，在空氣中的爆炸范圍為3-100%。釜內(nèi)溫度過高對(duì)生產(chǎn)存在較大的安全隱患ADDINEN.CITEADDINEN.CITE.DATA[7-9]，近年來多次出現(xiàn)以環(huán)氧乙烷為原料的生產(chǎn)出現(xiàn)不同程度的安全事故。鑒于這些強(qiáng)放熱反應(yīng)對(duì)產(chǎn)品品質(zhì)以及生產(chǎn)安全性和經(jīng)濟(jì)性帶來的影響，人們?cè)O(shè)計(jì)了很多反應(yīng)器類型，例如列管式反應(yīng)器ADDINEN.CITE<EndNote><Cite><Author>Tang</Author><Year>2008</Year><RecNum>20</RecNum><DisplayText><styleface="superscript">[10]</style></DisplayText><record><rec-number>20</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1584018785">20</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Tang,Zhiyong</author><author>Wang,Lianyuan</author><author>Yang,Jichu</author></authors></contributors><titles><title>Transesterificationofrapeseedoilcatalyzedbyliquidorganicamineinsupercriticalmethanolinacontinuoustubular-flowreactor</title><secondary-title>EuropeanJournalofLipidScienceandTechnology</secondary-title></titles><periodical><full-title>EuropeanJournalofLipidScienceandTechnology</full-title></periodical><pages>747-753</pages><volume>110</volume><number>8</number><dates><year>2008</year></dates><isbn>14387697 14389312</isbn><urls></urls><electronic-resource-num>10.1002/ejlt.200700256</electronic-resource-num></record></Cite></EndNote>[10]、塔式反應(yīng)器ADDINEN.CITE<EndNote><Cite><Author>Bouyahiaoui</Author><Year>2020</Year><RecNum>63</RecNum><DisplayText><styleface="superscript">[11]</style></DisplayText><record><rec-number>63</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586760869">63</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Bouyahiaoui,Hiba</author><author>Azzi,Abdelwahid</author><author>Zeghloul,Ammar</author><author>Hasan,AbbasH.</author><author>Al-Sarkhi,Abdelsalam</author><author>Parsi,Mazdak</author></authors></contributors><titles><title>Verticalupwardanddownwardchurnflow:Similaritiesanddifferences</title><secondary-title>JournalofNaturalGasScienceandEngineering</secondary-title></titles><periodical><full-title>JournalofNaturalGasScienceandEngineering</full-title></periodical><volume>73</volume><section>103080</section><dates><year>2020</year></dates><isbn>18755100</isbn><urls></urls><electronic-resource-num>10.1016/j.jngse.2019.103080</electronic-resource-num></record></Cite></EndNote>[11]、流化床反應(yīng)器ADDINEN.CITEADDINEN.CITE.DATA[12-14]、振蕩流反應(yīng)器ADDINEN.CITEADDINEN.CITE.DATA[15-20]、降膜反應(yīng)器ADDINEN.CITEADDINEN.CITE.DATA[21-22]以及微反應(yīng)器ADDINEN.CITEADDINEN.CITE.DATA[23-26]。根據(jù)每種反應(yīng)器的特點(diǎn)可適用于特定的反應(yīng)類型。本章對(duì)以環(huán)氧化合物為原料參與的反應(yīng)所用到的反應(yīng)器進(jìn)行了總結(jié)，也對(duì)本文所研究的兩個(gè)產(chǎn)品，進(jìn)行文獻(xiàn)介紹，在此基礎(chǔ)上提出本文的研究目的和內(nèi)容。1.2亞磷酸三(2-氯乙基)的合成路線及工藝亞磷酸三(2-氯乙基)酯ADDINEN.CITE<EndNote><Cite><Author>Mironova</Author><Year>1995</Year><RecNum>73</RecNum><DisplayText><styleface="superscript">[27]</style></DisplayText><record><rec-number>73</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586763416">73</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Mironova,O.Y.</author><author>Yanilkin,V.V.</author><author>Kormachev,V.V.</author></authors></contributors><titles><title>Electrochemicalbehavioroftris(2-chloroethyl)phosphateandtris(2-chloroethyl)phosphite</title><secondary-title>ZhurnalObshcheiKhimii</secondary-title></titles><periodical><full-title>ZhurnalObshcheiKhimii</full-title></periodical><pages>2001-2004</pages><volume>65</volume><number>12</number><dates><year>1995</year><pub-dates><date>1995</date></pub-dates></dates><isbn>0044-460X</isbn><accession-num>WOS:A1995UL16300012</accession-num><urls><related-urls><url><GotoISI>://WOS:A1995UL16300012</url></related-urls></urls></record></Cite></EndNote>[27]作為化工領(lǐng)域中的一種重要有機(jī)中間體。在農(nóng)藥領(lǐng)域，亞磷酸三(2-氯乙基)酯通常用于制備乙烯利。乙烯利是一種優(yōu)質(zhì)、高效的植物生長調(diào)節(jié)劑，具有促進(jìn)果實(shí)成熟、刺激\t"/item/%E4%B9%99%E7%83%AF%E5%88%A9/_blank"傷流、調(diào)節(jié)部分植物\t"/item/%E4%B9%99%E7%83%AF%E5%88%A9/_blank"性別轉(zhuǎn)化等功能ADDINEN.CITEADDINEN.CITE.DATA[28-31]。在消防領(lǐng)域，亞磷酸三(2-氯乙基)酯可作為合成四(2-氯乙基)亞乙基二磷酸酯阻燃劑ADDINEN.CITE<EndNote><Cite><Author>朱廣軍</Author><Year>1994</Year><RecNum>71</RecNum><DisplayText><styleface="superscript">[32]</style></DisplayText><record><rec-number>71</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586762565">71</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author><styleface="normal"font="default"charset="134"size="100%">朱廣軍</style></author></authors></contributors><titles><title><styleface="normal"font="default"charset="134"size="100%">阻燃劑</style><styleface="normal"font="default"size="100%">1_2_</style><styleface="normal"font="default"charset="134"size="100%">亞乙基四</style><styleface="normal"font="default"size="100%">_2_</style><styleface="normal"font="default"charset="134"size="100%">氯乙基</style><styleface="normal"font="default"size="100%">_</style><styleface="normal"font="default"charset="134"size="100%">二磷酸酯的新合成法</style></title><secondary-title><styleface="normal"font="default"charset="134"size="100%">化學(xué)通報(bào)</style></secondary-title></titles><periodical><full-title>化學(xué)通報(bào)</full-title></periodical><pages>35-36</pages><volume>2</volume><number>10</number><dates><year>1994</year></dates><urls></urls></record></Cite></EndNote>[32]的重要原料。四(2-氯乙基)亞乙基二磷酸酯通常作為一些有機(jī)聚合物的阻燃添加劑，具有相容性好、耐揮發(fā)、耐遷移、阻燃效果持久和毒性低等特點(diǎn)。1.2.1環(huán)氧乙烷與三氯化磷的合成路線1946年KabachnikMI和RossiiskayaPA首次報(bào)道了乙烯利的合成。通過環(huán)氧乙烷和三氯化磷作為初始原料，在低溫下進(jìn)行酯化反應(yīng)得到亞磷酸三(2-氯乙基)酯，然后再經(jīng)過高溫重排、酸解反應(yīng)合成乙烯利。在亞磷酸三(2-氯乙基)酯的反應(yīng)過程中一分子三氯化磷先與一分子環(huán)氧乙烷開環(huán)加成生成一分子單酯，這過程反應(yīng)迅速并且放出大量熱。然后一分子單酯與一分子環(huán)氧乙烷繼續(xù)反應(yīng)生成一分子二酯，二酯分子與環(huán)氧乙烷分子繼續(xù)反應(yīng)最終生成亞磷酸三(2-氯乙基)酯分子，如圖1-1。各產(chǎn)物生成的速率:單酯>二酯>三酯，如圖1-2。1995年姬學(xué)儀和朱德湘等人ADDINEN.CITE<EndNote><Cite><Author>姬學(xué)儀</Author><Year>1995</Year><RecNum>36</RecNum><DisplayText><styleface="superscript">[33]</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586592951">36</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author><styleface="normal"font="default"charset="134"size="100%">姬學(xué)儀</style></author></authors></contributors><titles><title><styleface="normal"font="default"charset="134"size="100%">亞磷酸三</style><styleface="normal"font="default"size="100%">_2_</style><styleface="normal"font="default"charset="134"size="100%">氯乙基</style><styleface="normal"font="default"size="100%">_</style><styleface="normal"font="default"charset="134"size="100%">酯的合成研究</style></title><secondary-title><styleface="normal"font="default"charset="134"size="100%">江蘇化工</style></secondary-title></titles><periodical><full-title>江蘇化工</full-title></periodical><pages>4-7</pages><volume>23</volume><number>3</number><dates><year>1995</year></dates><urls></urls></record></Cite></EndNote>[33]ADDINEN.CITE<EndNote><Cite><Author>姬學(xué)儀</Author><Year>1995</Year><RecNum>36</RecNum><DisplayText><styleface="superscript">[1]</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586592951">36</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author><styleface="normal"font="default"charset="134"size="100%">姬學(xué)儀</style></author></authors></contributors><titles><title><styleface="normal"font="default"charset="134"size="100%">亞磷酸三</style><styleface="normal"font="default"size="100%">_2_</style><styleface="normal"font="default"charset="134"size="100%">氯乙基</style><styleface="normal"font="default"size="100%">_</style><styleface="normal"font="default"charset="134"size="100%">酯的合成研究</style></title><secondary-title><styleface="normal"font="default"charset="134"size="100%">江蘇化工</style></secondary-title></titles><periodical><full-title>江蘇化工</full-title></periodical><pages>4-7</pages><volume>23</volume><number>3</number><dates><year>1995</year></dates><urls></urls></record></Cite></EndNote>在無催化劑條件下，環(huán)氧乙烷以液態(tài)形式與三氯化磷反應(yīng)制得亞磷酸三(2-氯乙基)酯，粗產(chǎn)品經(jīng)提純使得產(chǎn)品收率和純度分別達(dá)到98.5%和99.99%。同年吳少林ADDINEN.CITE<EndNote><Cite><Author>吳少林</Author><Year>1995</Year><RecNum>37</RecNum><DisplayText><styleface="superscript">[34]</style></DisplayText><record><rec-number>37</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586593394">37</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author><styleface="normal"font="default"charset="134"size="100%">吳少林</style></author></authors></contributors><titles><title><styleface="normal"font="default"charset="134"size="100%">亞磷酸三</style><styleface="normal"font="default"size="100%">_2_</style><styleface="normal"font="default"charset="134"size="100%">氯乙基</style><styleface="normal"font="default"size="100%">_</style><styleface="normal"font="default"charset="134"size="100%">酯異構(gòu)新工藝</style></title><secondary-title><styleface="normal"font="default"charset="134"size="100%">化學(xué)世界</style></secondary-title></titles><periodical><full-title>化學(xué)世界</full-title></periodical><pages>367-370</pages><volume>7</volume><dates><year>1995</year></dates><urls></urls></record></Cite></EndNote>[34]采用環(huán)氧乙烷以氣體形態(tài)與三氯化磷在25-30℃下制備亞磷酸三(2-氯乙基)酯。圖1-1環(huán)氧乙烷與三氯化磷反應(yīng)合成亞磷酸三(2-氯乙基)酯路線Figure1-1Synthesisoftris(2-chloroethyl)phosphitebyreactionofethyleneoxidewithphosphorustrichloride圖1-2釜式反應(yīng)下不同摩爾比的產(chǎn)物分布情況ADDINEN.CITE<EndNote><Cite><Author>姬學(xué)儀</Author><Year>1995</Year><RecNum>36</RecNum><DisplayText><styleface="superscript">[33]</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586592951">36</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author><styleface="normal"font="default"charset="134"size="100%">姬學(xué)儀</style></author></authors></contributors><titles><title><styleface="normal"font="default"charset="134"size="100%">亞磷酸三</style><styleface="normal"font="default"size="100%">_2_</style><styleface="normal"font="default"charset="134"size="100%">氯乙基</style><styleface="normal"font="default"size="100%">_</style><styleface="normal"font="default"charset="134"size="100%">酯的合成研究</style></title><secondary-title><styleface="normal"font="default"charset="134"size="100%">江蘇化工</style></secondary-title></titles><periodical><full-title>江蘇化工</full-title></periodical><pages>4-7</pages><volume>23</volume><number>3</number><dates><year>1995</year></dates><urls></urls></record></Cite></EndNote>[33]Figure1-2Distributionofproductswithdifferentmolarratiosinthekettlereaction1.2.2氯乙醇與三氯化磷的合成路線以氯乙醇與三氯化磷作為原料在一定條件下反應(yīng)可制得亞磷酸三(2-氯乙基)酯，并且伴隨氯化氫生成。部分氯化氫溶于反應(yīng)液中會(huì)與亞磷酸三(2-氯乙基)酯發(fā)生反應(yīng)，從而降低了產(chǎn)品中亞磷酸三(2-氯乙基)酯的含量。由于該反應(yīng)選擇性低下，僅為40%，并且在反應(yīng)過程中需要對(duì)氯化氫進(jìn)行吸收處理，增加了生產(chǎn)工序。從而一直未用于工業(yè)化生產(chǎn)，也很少有該合成路線的文獻(xiàn)報(bào)道。1.2.3亞磷酸三(2-氯乙基)酯的合成工藝在工業(yè)上有兩種亞磷酸三(2-氯乙基)酯的生產(chǎn)工藝，分別為傳統(tǒng)釜式工藝和微通道工藝。釜式生產(chǎn)工藝是將環(huán)氧乙烷氣體通入到裝有三氯化磷的一級(jí)反應(yīng)釜內(nèi)，通過冷卻系統(tǒng)使釜內(nèi)溫度維持在30℃左右，保溫8小時(shí)后轉(zhuǎn)移到二級(jí)反應(yīng)釜內(nèi)，釜內(nèi)溫度維持在40℃左右，進(jìn)一步保溫8小時(shí)后再一次轉(zhuǎn)移至三級(jí)反應(yīng)釜內(nèi)，釜內(nèi)溫度為50-60℃內(nèi)保溫8小時(shí)，以確保反應(yīng)完全。該酯化反應(yīng)是強(qiáng)放熱反應(yīng)，在生產(chǎn)中存在一些問題:(1)由于反應(yīng)釜的體積較大，換熱面積極為有限ADDINEN.CITE<EndNote><Cite><Author>陳曉君</Author><Year>2011</Year><RecNum>93</RecNum><DisplayText><styleface="superscript">[35]</style></DisplayText><record><rec-number>93</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586781267">93</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author><styleface="normal"font="default"charset="134"size="100%">陳曉君</style></author></authors></contributors><titles><title><styleface="normal"font="default"charset="134"size="100%">外夾套反應(yīng)釜與外半管反應(yīng)釜熱交換形式的對(duì)比分析</style></title><secondary-title><styleface="normal"font="default"charset="134"size="100%">廣東化工</style></secondary-title></titles><periodical><full-title>廣東化工</full-title></periodical><pages>166-178</pages><volume>38</volume><number>07</number><dates><year>2011</year></dates><urls></urls></record></Cite></EndNote>[35]。為了避免反應(yīng)釜內(nèi)的溫度過高，環(huán)氧乙烷的通氣速率僅為100~300kg/h，故生產(chǎn)一批亞磷酸三(2-氯乙基)酯的反應(yīng)周期較長，生產(chǎn)效率低下。(2)由于亞磷酸三(2-氯乙基)酯本身不太穩(wěn)定，在高溫度下易發(fā)生副反應(yīng)生成二聚體ADDINEN.CITE<EndNote><Cite><Author>Talos</Author><Year>2006</Year><RecNum>72</RecNum><DisplayText><styleface="superscript">[36]</style></DisplayText><record><rec-number>72</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586763416">72</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Talos,I.</author><author>Lupea,A.X.</author><author>Mihaila,C.T.</author><author>Bandur,G.</author></authors></contributors><titles><title>Thermicisomerizationfortris(2-chloroethyl)phosphiteandconsecutivetransformations</title><secondary-title>RevistaDeChimie</secondary-title></titles><periodical><full-title>RevistaDeChimie</full-title></periodical><pages>138-142</pages><volume>57</volume><number>2</number><dates><year>2006</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0034-7752</isbn><accession-num>WOS:000236716500006</accession-num><urls><related-urls><url><GotoISI>://WOS:000236716500006</url></related-urls></urls></record></Cite></EndNote>[36]，其中不對(duì)稱的二聚體在第三步酸解反應(yīng)中仍可以轉(zhuǎn)變?yōu)橐蚁├a(chǎn)品，但是對(duì)稱二聚體則無法進(jìn)行酸解，成為產(chǎn)品中的雜質(zhì)。亞磷酸三(2-氯乙基)酯還極易與水發(fā)生水解反應(yīng)，長時(shí)間存放于釜內(nèi)容易受潮轉(zhuǎn)變?yōu)楦碑a(chǎn)物，進(jìn)一步降低最終產(chǎn)品質(zhì)量。因此，采用釜式生產(chǎn)工藝得到的亞磷酸三(2-氯乙基)酯的含量最高僅能達(dá)到90%，嚴(yán)重制約了乙烯利原藥的品質(zhì)。除了釜式生產(chǎn)工藝，紹興市東湖生化有限公司開發(fā)了一種利用微通道制備亞磷酸三(2-氯乙基)酯的生產(chǎn)工藝ADDINEN.CITE<EndNote><Cite><RecNum>141</RecNum><DisplayText><styleface="superscript">[37]</style></DisplayText><record><rec-number>141</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586848124">141</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors></contributors><titles><title><CN104119374A.pdf></title></titles><dates></dates><urls></urls></record></Cite></EndNote>[37]。將液態(tài)環(huán)氧乙烷和三氯化磷通過連續(xù)泵輸送至耦合管道式預(yù)混合器進(jìn)行預(yù)混合(混合壓力為0.01~2MPa)，然后混合后的反應(yīng)液再進(jìn)入到微通道反應(yīng)裝置，同時(shí)開啟微通道反應(yīng)系統(tǒng)的冷媒冷卻設(shè)備，反應(yīng)完全后，收集微通道反應(yīng)裝置的流出液，即為亞磷酸三(2-氯乙基)酯產(chǎn)品原液。該裝置能夠穩(wěn)定連續(xù)制得流量為200~2000kg/h，含量為98%以上的產(chǎn)品。該微通道反應(yīng)裝置由1~10組微通道反應(yīng)器串聯(lián)構(gòu)成，微通道反應(yīng)器由50~500根管路組成，每根管路為Ф4mmx200mm的直管，每根管路盤旋在微通道反應(yīng)器內(nèi)，微通道反應(yīng)器的直徑為60mm，長為2000mm，見圖1-3。圖1-3微通道反應(yīng)裝置圖ADDINEN.CITE<EndNote><Cite><RecNum>141</RecNum><DisplayText><styleface="superscript">[37]</style></DisplayText><record><rec-number>141</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586848124">141</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors></contributors><titles><title><CN104119374A.pdf></title></titles><dates></dates><urls></urls></record></Cite></EndNote>[37]Figure1-3Microchannelreactiondevicediagram1.3N，N-雙羥乙基的合成路線及工藝N，N-雙羥乙基苯胺是化工領(lǐng)域中一種重要的有機(jī)中間體。在醫(yī)藥領(lǐng)域可被用于合成芳胺類活性藥，如N-甲基溶肉瘤素ADDINEN.CITE<EndNote><Cite><Author>Sidhu</Author><Year>1989</Year><RecNum>77</RecNum><DisplayText><styleface="superscript">[38]</style></DisplayText><record><rec-number>77</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586764926">77</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Sidhu,M.K.</author><author>Kumar,S.</author></authors></contributors><auth-address>SIDHU,MK(reprintauthor),UNIVMED&DENTNEWJERSEY,NEWJERSEYMEDSCH,DEPTBIOCHEM&MOLECBIOL,185SORANGEAVE,NEWARK,NJ07103,USA.</auth-address><titles><title>SYNTHESISANDSECRETIONOFPLASMINOGENACTIVATORSANDCOLLAGENASESINHUMAN-CELLSTRANSFORMEDBYKIRSTENMURINESARCOMA-VIRUSANDN-METHYL-N'-NITRO-N-NITROSOGUANIDINE</title><secondary-title>CancerLetters</secondary-title><alt-title>CancerLett.</alt-title></titles><periodical><full-title>CancerLetters</full-title><abbr-1>CancerLett.</abbr-1></periodical><alt-periodical><full-title>CancerLetters</full-title><abbr-1>CancerLett.</abbr-1></alt-periodical><pages>45-51</pages><volume>47</volume><number>1-2</number><keywords><keyword>Oncology</keyword></keywords><dates><year>1989</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0304-3835</isbn><accession-num>WOS:A1989AW58800006</accession-num><work-type>Article</work-type><urls><related-urls><url><GotoISI>://WOS:A1989AW58800006</url></related-urls></urls><electronic-resource-num>10.1016/0304-3835(89)90175-4</electronic-resource-num><language>English</language></record></Cite></EndNote>[38]、抗瘤氨酸ADDINEN.CITE<EndNote><Cite><Author>Minotti</Author><Year>2004</Year><RecNum>78</RecNum><DisplayText><styleface="superscript">[39]</style></DisplayText><record><rec-number>78</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586765186">78</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Minotti,G.</author><author>Menna,P.</author><author>Salvatorelli,E.</author><author>Cairo,G.</author><author>Gianni,L.</author></authors></contributors><titles><title>Anthracyclines:Molecularadvancesandpharmacologicdevelopmentsinantitumoractivityandcardiotoxicity</title><secondary-title>PharmacologicalReviews</secondary-title></titles><periodical><full-title>PharmacologicalReviews</full-title></periodical><pages>185-229</pages><volume>56</volume><number>2</number><dates><year>2004</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0031-6997</isbn><accession-num>WOS:000222021100002</accession-num><urls><related-urls><url><GotoISI>://WOS:000222021100002</url></related-urls></urls><electronic-resource-num>10.1124/pr.56.2.6</electronic-resource-num></record></Cite></EndNote>[39]和活性抗生藥。在染料行業(yè)中N，N-雙羥乙基苯胺和許多偶氮類物質(zhì)直接耦合制成染料。在聚合工業(yè)中N，N-雙羥乙基苯胺和過氧化苯甲酰合成醋酸乙烯聚合的引發(fā)劑，被用于不飽和樹脂聚合過程的硬化加速劑和交聯(lián)劑以及聚脲烷泡沫的鏈增長劑，使制得的聚合體具有較高的承載能力。在油漆工業(yè)中N，N-雙羥乙基苯胺用于制造丙烯酸漆的交聯(lián)劑，制得的漆和芳酮復(fù)配成耐曬能力的油漆。它還和糠胺等可配制成油漆清除劑，加速油漆的清除。在膠粘劑工業(yè)中，N，N-雙羥乙基苯胺能配制儲(chǔ)存穩(wěn)定性好的厭氧型壓敏粘合材料。它還可以和異氰酸酯等配制成建筑材料粘合劑和建筑路面粘合劑。1.3.1苯胺與環(huán)氧乙烷的合成路線LiCZ和ZhouSF等人ADDINEN.CITE<EndNote><Cite><Author>Li</Author><Year>2000</Year><RecNum>34</RecNum><DisplayText><styleface="superscript">[40]</style></DisplayText><record><rec-number>34</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1584627536">34</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Li,C.Z.</author><author>Zhou,S.F.</author><author>Fan,X.Z.</author><author>Zhu,Z.F.</author><author>Ding,Y.F.</author><author>Zhao,H.</author><author>Xia,C.G.</author><author>Wang,L.F.</author></authors></contributors><titles><title>Synthesis,characterization,andantitumouractivityofisonicotinamido-4-bis(2-chloroethyl)aminobenzaldiminecomplexesofsometransitionmetals</title><secondary-title>ChemicalPapers-ChemickeZvesti</secondary-title></titles><periodical><full-title>ChemicalPapers-ChemickeZvesti</full-title></periodical><pages>239-244</pages><volume>54</volume><number>4</number><dates><year>2000</year></dates><isbn>0366-6352</isbn><urls></urls></record></Cite></EndNote>[40]在異煙酰胺基-4-雙(2-氯乙基)氨基苯甲二胺的合成路線中所需的N，N-雙羥乙基苯胺中間體是由環(huán)氧乙烷氣體通入到含有1wt%乙酸的苯胺溶液(溫度<5℃)中，然后在2h內(nèi)將溶液溫度緩慢升溫至70℃后保溫20h。反應(yīng)結(jié)束后低壓條件下分離，得到N，N-雙羥乙基苯胺粗品，產(chǎn)率為90%，異煙酰胺基-4-雙(2-氯乙基)氨基苯甲二胺合成路線見圖1-4。圖1-4異煙酰胺基-4-雙(2-氯乙基)氨基苯甲二胺的合成路線ADDINEN.CITE<EndNote><Cite><Author>Li</Author><Year>2000</Year><RecNum>34</RecNum><DisplayText><styleface="superscript">[40]</style></DisplayText><record><rec-number>34</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1584627536">34</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Li,C.Z.</author><author>Zhou,S.F.</author><author>Fan,X.Z.</author><author>Zhu,Z.F.</author><author>Ding,Y.F.</author><author>Zhao,H.</author><author>Xia,C.G.</author><author>Wang,L.F.</author></authors></contributors><titles><title>Synthesis,characterization,andantitumouractivityofisonicotinamido-4-bis(2-chloroethyl)aminobenzaldiminecomplexesofsometransitionmetals</title><secondary-title>ChemicalPapers-ChemickeZvesti</secondary-title></titles><periodical><full-title>ChemicalPapers-ChemickeZvesti</full-title></periodical><pages>239-244</pages><volume>54</volume><number>4</number><dates><year>2000</year></dates><isbn>0366-6352</isbn><urls></urls></record></Cite></EndNote>[40]Figure1-4Isonicotinamido-4-bis(2-chloroethyl)aminobenzidinediaminesynthesisroute方線文和周麗珍等人ADDINEN.CITE<EndNote><Cite><Author>Fang</Author><Year>2013</Year><RecNum>38</RecNum><DisplayText><styleface="superscript">[41]</style></DisplayText><record><rec-number>38</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586593875">38</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Fang,Xianwen</author><author>Zhou,Lizhen</author><author>Cheng,Zhao</author><author>Yang,Meipan</author><author>Yang,Bingqin</author></authors></contributors><titles><title>Synthesis,CrystalStruturesandAntitumorActivityofNovelNitrogenMustard-LinkedChalcones</title><secondary-title>ChineseJournalofOrganicChemistry</secondary-title></titles><periodical><full-title>ChineseJournalofOrganicChemistry</full-title></periodical><volume>33</volume><number>3</number><section>523</section><dates><year>2013</year></dates><isbn>0253-2786</isbn><urls></urls><electronic-resource-num>10.6023/cjoc201211041</electronic-resource-num></record></Cite></EndNote>[41]在含氮芥基查爾酮類衍生物的制備中所需的N，N-雙羥乙基苯胺中間體，采用以丙酸作為催化劑，將環(huán)氧乙烷氣體通入到-5℃的苯胺溶液中過夜反應(yīng)，TLC監(jiān)測(cè)至苯胺原料點(diǎn)消失，將反應(yīng)液倒入分液漏斗中，靜置分層，有機(jī)相用飽和Na2CO3水洗，無水MgSO4干燥過夜，減壓蒸出溶劑，殘余物經(jīng)硅膠柱色譜，得白色固體。N，N-雙羥乙基苯胺收率為90%。查爾酮化合物的合成路線，見圖1-5。圖1-5查爾酮化合物的合成路線ADDINEN.CITE<EndNote><Cite><Author>Fang</Author><Year>2013</Year><RecNum>38</RecNum><DisplayText><styleface="superscript">[41]</style></DisplayText><record><rec-number>38</rec-number><foreign-keys><keyapp="EN"db-id="ztw92e5faa05tdewp53pr99ur9fra52awtpd"timestamp="1586593875">38</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Fang,Xianwen</author><author>Zhou,Lizhen</author><author>Cheng,Zhao</author><author>Yang,Meipan</author><author>Yang,Bingqin</author></authors></contributors><titles><title>Synthesis,CrystalStruturesandAntitumorActivityofNovelNitrogenMustard-LinkedChalcones</title><secondary-title>ChineseJournalofOrganicChemistry</secondary-title></titles><periodical><full-title>ChineseJournalofOrganicChemistry</full-title></periodical><volume>33</volume><number>3</number><section>523</section><dates><year>2013</year></dat