Organic synthesis
A-Level Chemistry Topic 21 8:01 English narration · English + 中文 subtitles burned in
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Look at almost any medicine.
看看几乎任何一种药物。
It is a complicated molecule, and it began as something simple — often a small molecule from crude oil.
它是一个复杂的分子，而它最初来自很简单的东西—— 往往是石油里的一个小分子。
No single reaction turns one into the other.
没有哪一个反应能一步做到。
Chemists get there step by step, joining together reactions they already know. The exam does the same thing to you.
化学家是一步一步走过去的，把已经学过的反应连接起来。
Here is your starting material. Here is your target. Find the path.
考试也这样考你： 这是起始物，这是目标分子，请你找出路径。
Welcome to organic synthesis.
欢迎来到有机合成。
This topic adds no new reactions. It teaches you to join up the reactions you already have.
这一章不增加新的反应，而是教你把已经学过的反应连起来。
First, recognise the functional groups. Then travel across the reaction map. Then plan a synthetic route by working backwards from the target.
第一步，识别官能团；第二步，在反应图上"走路"；第三步，从目标分子倒推， 规划一条合成路线。
First, work out which functional groups you have.
首先要弄清楚分子里有哪些官能团。
Five simple tests do most of the work.
五个简单的试验几乎能解决全部问题。
Bromine water goes from orange to colourless: a carbon to carbon double bond, so an alkene.
溴水由橙色褪成无色：说明有碳碳双键，也就是烯烃。
Silver nitrate gives a precipitate: a halogenoalkane.
硝酸银出现沉淀：卤代烷。
Orange potassium dichromate turns green: a primary or a secondary alcohol.
橙色的重铬酸钾变绿：伯醇或仲醇。
Brady's reagent gives an orange precipitate: an aldehyde or a ketone.
布雷迪试剂出现橙色沉淀：醛或酮。
And fizzing with a carbonate: a carboxylic acid.
与碳酸盐反应冒泡：羧酸。
Now the harder version. One molecule can carry more than one functional group.
再来看更难的情形：一个分子可以带不止一个官能团。
Take lactic acid, the acid in yogurt and in tired muscles: a carboxylic acid at one end, a secondary alcohol in the middle.
以乳酸为例—— 它存在于酸奶和疲劳的肌肉里。 它有两个官能团：一端是羧酸，中间是仲醇。
Each group keeps its own chemistry.
每个官能团都保留自己的化学性质。
The acid fizzes with a carbonate; the alcohol is oxidised by hot acidified dichromate, and being secondary, it gives a ketone.
羧酸基与碳酸盐反应冒泡； 醇基被热的酸化重铬酸钾氧化，而由于它是仲醇，产物是酮。
So always ask two questions. What will each group do?
所以要问两个问题：每个官能团会做什么？
And will my reagent attack a group I wanted to keep?
我的试剂会不会破坏我想保留的那个基团？
Here is the whole thing on one page. Nine kinds of molecule, joined by reactions you already know.
这就是全部内容，画在一张图上：九类分子，由你已经学过的反应连接起来。
Start on the left with the alkene, from crude oil.
从左边的烯烃开始，它来自石油。
Add hydrogen for an alkane; add a hydrogen halide for a halogenoalkane.
加氢就得到烷烃；加卤化氢就得到卤代烷。
That halogenoalkane is the busiest junction on the map: it leads to an amine, to a nitrile, and to an alcohol.
卤代烷是图上最繁忙的路口：它通向胺、通向腈，也通向醇。
On the right, the molecule climbs a ladder: alcohol, then aldehyde or ketone, then carboxylic acid — where the nitrile route rejoins.
在右边，分子沿着一架梯子往上爬：醇，然后是醛或酮，再是羧酸—— 腈的那条路也在这里汇合。
And one last arrow makes an ester, from that acid and an alcohol, warmed with concentrated sulfuric acid.
最后还有一个箭头生成酯： 由这个羧酸和一种醇，用浓硫酸加热制得。
Learn this map, and a synthesis question becomes finding a path across it.
记住这张图， 合成题就变成了在图上找一条路径。
Zoom in on the alkene.
我们放大看烯烃。
Its double bond is a loose, electron-rich pair, so the alkene reacts by addition: the bond opens and something joins on.
它的双键是一对松散的、富电子的电子，所以烯烃以加成反应进行： 双键打开，别的东西加上去。
Three additions matter here.
这里有三个重要的加成。
Hydrogen with a nickel catalyst gives the alkane. A hydrogen halide gives the halogenoalkane. And steam, over a phosphoric acid catalyst, gives the alcohol — a one-step way into the whole oxidation ladder.
氢气加镍催化剂，得到烷烃； 卤化氢，得到卤代烷；水蒸气加磷酸催化剂，得到醇—— 这是一步进入整条氧化梯子的通道。
Watch that addition closely.
仔细看这个加成。
Hydrogen bromide is polar, so the double bond reaches out and grabs its hydrogen.
溴化氢是极性的，氢的一端带部分正电荷， 富电子的双键就伸过去把它抓住。
The more stable of the two possible ions then wins.
两种可能的碳正离子中，较稳定的那个胜出。
That is Markovnikov's rule: the hydrogen joins the carbon that already has more hydrogens.
这就是马氏规则：氢加到本来含氢较多的那个碳上。
So with propene, the new group lands on the middle carbon.
所以对丙烯来说， 新的基团落在中间那个碳上。
Now that busy junction.
再来看那个繁忙的路口：卤代烷。
The halogenoalkane's carbon to halogen bond is polar, so a nucleophile can replace the halogen.
它的碳卤键是极性的， 所以亲核试剂可以进来把卤原子取代掉。
Three reagents, three products.
三种试剂，三种产物。
Aqueous sodium hydroxide, heated, gives the alcohol.
氢氧化钠水溶液加热，得到醇。
Potassium cyanide in ethanol, heated, gives a nitrile — and that one adds a carbon to the chain.
氰化钾的乙醇溶液加热，得到腈—— 而且这一步会给碳链增加一个碳原子。
Ammonia in ethanol, under pressure, gives an amine.
氨的乙醇溶液加压，得到胺。
All three are the same move: nucleophilic substitution.
这三步是同一个动作：亲核取代。
And a nitrile is not a dead end: warm it with dilute acid and it becomes a carboxylic acid.
腈也不是死路：用稀酸温热，它就变成羧酸。
The right of the map is a ladder, and acidified potassium dichromate takes you up it.
反应图的右半边是一架梯子，酸化的重铬酸钾带你往上爬。
A primary alcohol goes up two rungs. Distil the product off as it forms and you stop at the aldehyde; reflux it instead and it goes all the way to the carboxylic acid.
伯醇要上两级： 边生成边蒸出产物，就停在醛；改成回流加热，就一直到羧酸。
A secondary alcohol has one rung to climb: reflux gives a ketone and stops there. A tertiary alcohol does not react at all.
仲醇只有一级可爬：回流得到酮，然后就停住了。
And sodium borohydride takes you back down, turning an aldehyde or ketone into an alcohol.
叔醇根本不反应。 而硼氢化钠带你往下走，把醛或酮变回醇。
Now the method. Four steps, and they work every time.
接下来是方法，四个步骤，每次都管用。
First, compare the target with the starting material: what changed?
第一，把目标分子和起始物作比较： 什么变了？ 是官能团？
The functional group?
还是碳原子数？
The carbon count? Second, work backwards from the target — which single reaction could make it, and from what?
第二，从目标分子往回推： 哪一个反应能生成它，又是由什么生成的？
Third, repeat that until you reach your starting material.
第三，重复这样往回推， 直到回到起始物。
Fourth, write the route out forwards, with a reagent and its conditions on every arrow.
第四，再正着把路线写出来，每一个箭头都写上试剂和条件。
Let's do one.
我们做一道。
From propene, make propanone.
从丙烯出发制丙酮。
Start at the target and work backwards.
先站在目标分子上往回推。
Propanone is a ketone, and a ketone comes from oxidising a secondary alcohol. So the step before is propan-2-ol, under reflux with acidified potassium dichromate.
丙酮是酮，而酮来自仲醇的氧化，所以上一步是丙醇-2， 用酸化的重铬酸钾回流加热。
And where does propan-2-ol come from?
那么丙醇-2 又从哪里来？
From propene plus steam over a phosphoric acid catalyst — Markovnikov puts the new group on the middle carbon, exactly the secondary alcohol we need.
来自丙烯加水蒸气、以磷酸作催化剂——而且马氏规则把新基团放在中间的碳上， 正好就是我们需要的仲醇。
So the finished route is two steps.
所以最终的路线是两步。
Now the one from the very beginning. From ethene, make propanoic acid.
现在回到一开始那道题：从乙烯制丙酸。
Look at the carbon count first: two carbons must become three, so the cyanide step has to be in there.
先看碳原子数： 乙烯有两个碳，丙酸有三个碳，所以氰化物那一步一定要出现。
Pause here and try it yourself.
先暂停，自己试一试。 好了吗？
Ready? Propanoic acid comes from hydrolysing propanenitrile with dilute acid. Propanenitrile comes from bromoethane with potassium cyanide in ethanol.
丙酸来自丙腈用稀酸水解； 丙腈来自溴乙烷与氰化钾的乙醇溶液反应；而溴乙烷来自乙烯加溴化氢。
And bromoethane comes from ethene plus hydrogen bromide. Three steps, and the extra carbon arrives in the middle one.
一共三步，多出来的那个碳是在中间那一步加上去的。
Sometimes the exam gives you the route and asks you to analyse it.
有时考试直接给你一条路线，要你去分析它。
For every step, name the type of reaction, and give the reagent and its conditions.
对每一步， 都要写出反应类型，并给出试剂和条件。
Five types cover it.
你需要掌握五种类型。
Addition: two molecules become one — an alkene taking on hydrogen bromide.
加成： 两个分子合成一个，比如烯烃与溴化氢反应。
Substitution: one group replaces another — hydroxide replacing a halogen.
取代：一个基团被另一个替换， 比如氢氧根取代卤原子。
Elimination: a small molecule is removed — an alcohol losing water to give an alkene.
消去：脱去一个小分子，比如醇脱水生成烯烃。
Oxidation climbs the ladder; reduction brings you back down.
氧化让分子沿梯子往上，还原则把它带回来。
And by-products, which examiners love.
再来说副产物，这是考官很喜欢的一点。
Every step loses some material, so a longer route gives a lower overall yield: three steps at seventy per cent each leave you only about a third.
每一步都会损失一些物质， 所以路线越长，总产率越低：三步、每步百分之七十，最后只剩下大约三分之一。
Ammonia is the classic example: the amine it makes is itself a nucleophile, so it attacks another molecule and you get a mixture of amines. Use a large excess of ammonia.
氨就是经典例子：它生成的胺本身也是亲核试剂，会去进攻另一个分子， 结果得到一堆胺的混合物，所以要用大量过量的氨。
And conditions are not decoration — aqueous sodium hydroxide gives you the alcohol, but the same hydroxide, hot in ethanol, removes a hydrogen halide and gives an alkene.
另外，条件不是装饰品：氢氧化钠水溶液给你醇， 而同样的氢氧化钠在热的乙醇中却会脱去卤化氢，生成烯烃。
Three marks students throw away.
三个学生常丢的分。
First, every arrow needs a reagent and its conditions — the right intermediates with no reagents score almost nothing.
第一，每一个箭头都要写试剂和条件—— 中间产物都写对、却不写试剂，几乎拿不到分。
Second, check the carbon count. Only a cyanide can lengthen the chain: potassium cyanide with a halogenoalkane, or hydrogen cyanide with an aldehyde or a ketone.
第二，检查碳原子数： 只有氰化物能加长碳链——氰化钾与卤代烷反应，或者氰化氢与醛或酮反应。
Third, choose the shortest valid route, because fewer steps means a higher yield.
第三，选最短的有效路线：步骤越少，产率越高。
Get those right, and this topic is yours.
把这三点做对， 这个专题就是你的了。