配方实验记录，好、坏、丑的区别

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来听听这位在美国做有机化学实验的学者讲述如何写实验记录：

我在国内高校研究生院做了三年合成实验，在美国高校研究生院做了五年合成实验，而在药厂又做了三年合成实验。在此把我的经历作个比较，供大家参考。
我那时在国内高校做实验，实验记录本是从仓库领的，和街上买的普通笔记本并无不同。对如何记录实验也并无统一详尽规定，我的记忆中导师只说了一句话，实验要如实记录，其他的细节就留给我掌握了。

但初进美国研究生院时，情景可大不一样。记得专有一英文课，详细讲述做科研的道德规范和作抄袭的种种情况，等到进了科研组，导师郑重其事地亲手交给每个新生一本厚厚手册，一本他自己当年的实验记录本，和一篇组里前辈论文的支持数据材料。

他指着这数据说，"...respect these is moreimportant than (respect) me...",等到进了公司，关于如何记录实验就有更专门的规定，而且每年有小测试，确保每个做实验的人明了各个细节。

我现将我导师写的关于实验记录本的部分规定翻译出来，供大家欣赏借鉴。 

-原始科学数据

-无二的真相

-实验记录的目的是为其他的科研人员，不是做实验的本人。
-他人应能凭之重复实验，观测到同样现象，得到同样结果。

-封皮有人名，序列号，研究方向
-有目录/索引
-依次记录，不可移去任一页
-每个实验新起一页，不可空页，跳行记录
-划去每页空白
-页底签名
-记录时直接在本上用黑墨水写，不可涂改，用单化线划去笔误并附脚注

-有标题和日期
-配平的反应方程式；试剂的用量(质量或体积，如体积标出密度)，摩尔数，当量数，来源，CAS 号，纯度，物性参数如熔沸点，旋光度等
-注意有效数字
-特殊条件标出如玻璃干燥细节，无氧无水或无光操作等
-所依文献或已做实验
-记录所有相关操作细节(时间，温度，加料方式等) 
-记录所有现象(色，溶，沉淀，气)等
-复印TLC，GC，HPLC 
-记录实验后处理工序(萃取，洗涤所用容积；干燥剂；蒸馏时间，压力，温度) 
-注意检查质衡
-详尽记录纯化步骤(重结晶，溶剂，体积，温度，是否活性炭处理，收率；蒸馏，所用玻璃仪器，真空度，蒸馏头温度，内温，浴温，每个馏分质量；走柱子，溶剂，硅胶量，每级分量和RF值)。
-纯化样计算收率
-纯化样用所在notebook 页数标号；其相应数据如谱图等以此标号注明归档。
-结语，实验结果，解释，可能改进建议
-附图谱 NMR, IR, MASS, 结构式，谱上注化合物名，人名
-附色谱GC，HPLC，柱型，长度，温度，压力，流量
-对手性化合物，消旋样分离色谱，旋光物分离色谱；测旋光
-签名公正 

随着数字化转型的深入，越来越多的工程师开始使用配方研发系统，实现智能配方研发、并将AI人工智能引入到配方实验过程中，因此，原来纸质的试验记录本也将由电子实验记录替代，企业家精细化工配方研发系统是一套专业的配方试验管理系统，能够实现研发数据的积累和数字分析，实现配方及工艺的优化。

1. 添加试剂

To a mixture (suspension / solution / slurry) of compound 12 (487 mg, 1 mmol) and  o-plenylenediamine (648 mg, 6 mmol) inCH ₂Cl ₂(15 mL) being cooled to 0 ^oC was added the DCC (226 mg, 1.1 mmol).

Anhydrous lithium iodide (1.38 g, 10.3 mmol) was added the five portions (dropwise/ in one portion / in portions) to a stirred solution of compound 12 (10.93 g, 51.5mmol) in CH ₂Cl ₂(120 mL).

A round-bottom flask was charged with compound 3 (1.75 g, 5.27 mmol), LiCl (1.17 g, 26.3 mmol), DMSO (100 mL) and H ₂O (378 ul)

2. 催化量的

Et ₃N (20 mL, 142 mmol) and a catalytic amount of DMAP were added the solution of compound 1 (4.549 g, 46.4mmol) in CH ₂Cl ₂(120 mL) at 0 ^oC

3.气体保护

To a stirred -78 ^oC solution of trimethylsilyacetylene (4.44 g, 45.5 mmol) in THF (10 mL) under Argon was added dropwise  n-butylithium (1.6 M in hexane, 28.25 mL).

4. 通入气体

An ozone-enriched steam of oxygen was bubbled througha cold (-78 ^oC) solution of compound 9 (128 mg, 1.409 mmol) in CH ₂Cl ₂ (5 mL) untilit turned light blue. The solution was purged with argon at -78 ^oCfor 10 min to remove the excess O ₃.

5. 通过双针头导管加料

The mixture was added to a solution of compound 2 (3.00 g, 12.8 mmol) in THF (48mL) via cannula over a period of 30 min.

A solution of compound 29 (100 mg, 0.19 mmol, 1.0 equiv) in dry DMSO (1.5 mL) wascannulated under Argon to a vigorously stirred mixture of powered potassiumsuperoxide (62 mg, 0.87 mmol, 4.5 equiv) and 18-crown-6-ether (23 mg, 0.087mmol, 0.45 equiv) in dry DMSO (0.5 mL).

6. 通过注射器加料

To a stirred solution of compound 15 (8.61 g, 21.2 mmol)was added a solution of  p-toluenesulfonicacid (6.0 g) in CH ₂Cl ₂via syringe over 5 min.

1. 反应检测

After 1 h, TLC analysis (CH ₂Cl ₂/ hexane 3:1) showed the complete consumption of compound 15.

2. 放置过夜

The mixture was left standing overnight.

3. 甲苯/乙醇带水

Compound A(1.97 g, 6.63 mmol) was coevaporated with toluene five times to remove the water. The residue was subjected to toluene azeotrope to givethe corresponding acid chloride as brown oil. The aqueous portion was concentrated underreduced pressure followed by azeotropic removal of water with absolute EtOH

4. 氢化反应

A mixture of compound 1 (190 g, 0.88mmol) and Raney Ni (20 g) inethanol (1500 mL) and ethyl acetate (500 mL) was stirred under 1 atm at room temperaturefor an hour.

5. 分水器

A mixture of TsOH.H ₂O (56.91 g, 0.3 mol) and toluene (400 mL) was heated to reflux to remove water by Dean-Stark trap.

6. 反应放热

The reaction was exothermic.

7. 微波反应

The sealed vial was irradiated in the microwave on a Biotage Smith Synthesis at 150 ^oC for 10 min.

1. 过滤

The mixture was filtered through a Celite pad, and thefiltrate was concentrated to give the crude product.

2. 淬灭

The reaction mixture was quenched by the addition of thesaturated aqueous NH ₄Cl.

3. 磨碎

The residue was triturated with ether and filtered to afforda white solid.

4. 在两相中分开

The residue was partitioned between ethyl acetate (100mL) and HCl (1 M aq., 50mL). The organic layer was washed with water, dried (MgSO ₄) andevaporated to dryness. Ethyl acetate (100 mL) and HCl (1 M aq., 50 mL) were added to the residue,and the layers were separated.

5. 静止固化

The crude product was purified by prep-HPLC to givecompound 4as colorless thick oil,which was solidified on standing.

6. 在冻干机冻干

The white solid was re-crystallized from water, driedby hyophilization to give a white solid.

7. 纯化

过柱：The crude product was chromatographed on silica gel(CH ₂Cl ₂ / MeOH 20:1→10:1→5:1) to give the compound 8 (0.282 g,51%) as a white solid. The crude product was purified by column chromatographyon silica gel eluted with (CH ₂Cl ₂ / MeOH，20:1→10:1→5:1) to give the compound 8 (0.282 g, 51%) as a white solid.

制备HPLC纯化:be purified by prep-HPLC to afford/give/yield

制备TLC纯化:be purified by prepare TLC to afford/give/yield

重结晶:recrystallized from

8. 调 pH

The pH was adjusted to around 9 by progressivelyadding solid NaHCO ₃

The mixture was adjusted to pH 9 with solid NaHCO ₃

9. 萃取

The aqueous layer was extracted with ethyl acetate (100mL × 4).

10. 浓缩

The mixture was evaporated to afford the crudeproduct.

The mixture was concentrated afford the crude product.

The solvent was removed to afford the crude product.

11. 干燥

干燥：The organic layer was dried over MgSO ₄, andconcentrated.

真空干燥：The precipitate was filtered and dried in vacuo (in/ undervacumm; under reduced pressure).

1. 加料放热

A gentle reflux appeared throughout the addition

Heat generated during the addition.

The temperature was increased from 25 ^oC to50 ^oC during the addition.

2. 反应过程中或者降温有固体析出

Solid was precipitate out after 1h reaction.

The reaction mixture was cooled to -10 ^oC,and solid was precipitate out.

3. 加料不溶解

XX was added to the mixture, and the resultingsuspension was stirred for 2hrs.

4. 加热溶解

The suspension was heated to 90 ^oC and stirred until all solid was dissolved.

5. 反应变粘稠/变色

The reaction mixture became sticky after 2hr sreaction/stirring.

After 2hrs stirring, the mixture turned into black/brown/gray/yellow/red color.

1. 无进一步处理

No further operation

2. 统一和其他批次一起后处理

The work-up of this batch was together with the other batches that recorded in the following pages.

3. 检测条件，不需要后处理

IPC check showed this condition is better/bad for this reaction.  No further operation for condition screen reaction.