What is Chemical Reaction

We see a lot of chemical reactions in our daily life all the time. Fire, respiration, and cooking all involve chemical reactions. To put it in a simple way, chemical reaction is any transformation from one set of chemicals into another set.

Since we can’t see the chemicals at molecular level, we will need to see the change which is visible to naked eye to confirm that a chemical reaction has occurred. A chemical reaction is often accompanied by a temperature change, bubbles, color change, or precipitate formation.

Usually, chemical properties permanently change. Let us take an example. Consider our breakfast, we start with raw eggs and then cook them in a skillet. In the end we have very different eggs than what we started with. They not only do they look different physically, but you have also permanently changed the structure of the eggs' proteins. No longer a runny clear liquid, eggs are solid, bright white, and very yummy… J

Take another example, Melting ice does nothing to change the chemical properties of the water itself, like we just saw with eggs. It might be in a different phase, but we can easily re-freeze the water back into ice and this will be the same ice which we started with. No permanent physical changes occurred.

How to make Colored Fire...

Well we can’t get green color flame if we throw green color paper into fire. There is some science behind the colored fire. I have tried to put it in the simplest way possible procedure to produce colored fire in safe and easy way.

It is actually the different chemicals used which produce the different color. Below listed are some of the chemicals and the colors which they produce when burnt.

• Blue  - Cupric chloride
• Red  -  Lithium chloride
• Red   - Strontium chloride
• Green -  Cupric sulfate
• Orange -  Borax (Sodium borate)
• Orange  - Calcium chloride
• Purple -  Potassium chloride
• Yellow  - Sodium chloride
• Yellow  - Sodium carbonate
• Blue   - Cupric chloride
• Red   - Lithium chloride
• Red   - Strontium chloride
• Green  -  Copper sulfate
• Orange  -  Sodium borate
• Orange  - Calcium chloride
• Purple   - Potassium chloride
• Yellow   - Sodium chloride
• Yellow   - Sodium carbonate
• White sparks  - Magnesium ribbon
• Yellow sparks  -  Iron filings

How to do it: Take a plastic container and add a gallon of water. To this add roughly around 400 grams of any of the above chemical and mix it well to form  a solution (most of the above salts are water soluble). Now take your dried material (wood logs, wood chips or any other fire source , preferably wood) and soak it in the above prepared chemical solution for one day. Now take the soaked material and dry it until all the water has dried up. By now the chemical must have been absorbed onto the fire source very well. Now just burn the wooden logs like how you do with your normal wooden logs and enjoy a cool color fireplace. Use multiple colored soaked logs for multiple fire colors. Make sure to use proper safety equipment will preparing these.

Note: You can proportionately add the chemical to water. i.e. you can add even 200 grams to half gallon of water also.

Electronic Lab Notebooks- More organised, streamlined, secure and easier to search and share..??

For the past 6 years I worked as a research scientist in pharma industry working on synthesis of various molecules.  All these years I documented the procedures in paper based notebooks and ended up having several sets of notebooks.  Now today all of a sudden I started thinking why don’t we start using electronic lab notebooks.  I feel they can be organised much more easily and stored much more securely than the physical books which we generally use.

Also it makes searching of procedures easier for us.  Say you want search for a particular conversion lets say you want synthesise 2-formyl indole and someone from your company might have already worked on it which you don’t know.  Instead of searching on Scifinder (for which u have to pay) or internet, you can start the initial search with your in-house procedures first i.e. with the help of electronic lab note book.  This makes your search a lot easier.

I haven’t personally used any electronic lab notebook till now and also feel they are more expensive for any small pharma company to afford and maintain them, but thanks to the software companies who create these.  We have basic versions of e-LNB available on internet for free.  We can always upgrade to more advanced version with enhanced features but for a price.

If anyone of you reading this has the experience of using a e-LNB please put in your experiences working with them. 

I also feel paper based lab notebooks are the best sometimes as it presents our work in real synonymous with our mind while working…J

Some of the freely available ELNB on internet have been listed below for your convenience.

http://www.labtrack.com/
http://www.aejournal.net/content/1/1/4
http://www.contur.com/home/
http://www.sparklix.com/
http://accelrys.com/products/eln/

For a detailed review of various e-LNB available in market you can visit the following publication from Journal of Laboratory Automation.  Click here..>

Acyloin Condensation

Acyloin Condensation is a coupling reaction in which two carboxylic acid esters couple in the presence of metallic sodium under inert atmosphere to yield an α-hydroxyketone (also known as acyloin).

This reaction is favoured when R is an long chain alkyl group and also when high boiling solvents are used. Intramolecular condensation also takes place leading to closed rings of different sizes (like paracyclophanes or catenanes). But again this all depends on ring size and steric properties, but independent from high dilution. Intramolecular cyclisation over intermolecular polymerisation in diesters.

If the condensation is carried out in the presence of proton donor like alcohol then reduction of ester to alcohol takes place. This reaction is also called as Bouveault-Blanc Reduction.

Mechanism of Acyloin Condensation

Above mechanism involves

(1) Oxidative ionization of two sodium atoms on the double bond of two ester molecules.

(2) Free radical coupling between two molecules of the homolytic ester derivative (A Würtz type coupling). Alkoxy-eliminations in both sides occur, producing a 1,2-diketone.

(3) Oxidative ionization of two sodium atoms on both diketone double bonds. The sodium enodiolate is formed.

(4) Neutralization with water to form the enodiol, which tautomerizes to acyloin.

The enediolate intermediate is trapped as the bis-silyl derivative by the use of trapping agent chlorotrimethylsilane. This intermediate can be isolated and subsequently hydrolysed under acidic condition to the acyloin, which gives a better overall yield. Toluene, dioxane, THF or dialkylethers may be used and in some cases NMP (I am not sure of this) may also be used.

Literature references:

(1) Acyloin condensation in which chlorotrimethylsilane is used as a trapping agent
     Organic Syntheses, Coll. Vol. 6, p.167 (1988); Vol. 57, p.1 (1977).

(2) The Acyloin Condensation of Aralkyl Esters
      J. Am. Chem. Soc., 1952, 74 (19), pp 4861–4864

(3) The Formation of Five- and Six-membered Rings by the Acyloin Condensation.
      J. Am. Chem. Soc., 1957, 79 (22), pp 6050–6055

(4) Mechanism of the acyloin condensation
     J. Org. Chem., 1975, 40 (4), pp 393–402

Predicting Proton Chemical Shift Values

Many at times we have found it tough to predict the right chemical shift for a proton. Especially if you have just come out of college and started your research.  But I am sure with some practice and skill you will master this..:)

Below I have put a proton shift values table so that you can easily predict which proton comes at what chemical shift. Remember you cannot exactly predict the shift value but come you predict the narrow range the proton falls in.

Please note that all these values have been taken in deuterated chloroform.

If you need some practice on this you may visit the following link on the chemistry department's page of University of Wisconsin. click here.

Or you can also view the below lecture by sarutahiko on youtube to get more understanding on this topic.

Claisen Condensation

The Claisen condensation (different from  Claisen rearrangement) is a C-C bond forming reaction that occurs between two esters or one ester and another carbonyl compound in the presence of a strong base (like sodium ethoxide), resulting in a β-keto ester or a β-diketone.  It is named after Rainer Ludwig Claisen (German Chemist), who first published his work on the reaction in 1881.

The base used must not interfere with the reaction by undergoing nucleophilic substitution or addition with a carbonyl carbon. For this reason, the conjugate sodium alkoxide base of the alcohol formed (like sodium ethoxide if ethanol is formed) is often used, since the alkoxide is regenerated. In some cases LDA (lithium diisopropylamide) a non nucleophilic base is used (e.g. mixed claisen condensation)

The alkoxy portion of the ester must be a relatively good leaving group. Methyl and ethyl esters, which yields methoxide and ethoxide, respectively, are commonly used.

The driving force is the formation of the stabilized anion of the β-keto ester. If two different esters are used, an essentially statistical mixture of all four products is generally obtained, and the preparation does not have high synthetic utility.

However, if one of the ester partners has enolizable α-hydrogens and the other does not (e.g., aromatic esters or carbonates), the mixed reaction (or crossed Claisen) can be synthetically useful. If ketones or nitriles are used as the donor in this condensation reaction, a β-diketone or a β-ketonitrile is obtained, respectively.

The use of stronger bases (like sodium amide or sodium hydride) instead of sodium ethoxide, often increases the yield.

Mixed Claisen Condensation (Reaction between enolizable ester or ketone and a nonenolizable ester)

Intramolecular Claisen Condensation (Reaction where a molecule with two ester groups reacts intramolecularly, forming a cyclic β-keto ester.  This is also called as Dieckmann Condensation)

Purifying Organic Compounds

Purifying organic compounds in lab can be very challenging sometimes.  If you planning to use column purification you may end using lot of solvents and also your time.  Instead you can try some recrystallisation techniques for some large scale purifications.  These can also work for small scale but be wise in judging whether you want try RC’s for milligrams scale as sometimes column purification is best for milligrams and grams scale purification if you want to save time finding out right techniques unless you are developing a process though.

Below mentioned are some of the techniques which I do.  I just mentioned the rough idea and not a very detailed procedure here.

Idea 1: Try to dissolve your compound in acetone.  If it doesn't dissolve in acetone at rt then try to heat gently to make it dissolve.  Then bring the solution to rt and try to add water slowly (your compound should be water insoluble) and see whether your compounds precipitates out pure or not.

Try repeating this other water soluble solvents like Methanol, ethanol, IPA..etc

Idea 2: This is hot slurry techniques.  Make a stirrable slurry of your compound in solvents like ethyl acetate, MTBE, DCM (low boiling so be careful while heating)…etc..Stir the slurry under hot conditions and bring down the temperature to rt and filter.  You can try different temperatures for this slurry.  My idea is to try with the high temperature first and go to low temperature.

Hot filtration can also be done but I do not recommend it for large scale purifications and its risky.  For grams scale you can try hot filtration.

Idea 3:  dissolve your compound in more polar solvent like ethyl acetate or DCM and try to precipitate it with by adding a non-polar solvent like hexanes or heptanes an check for any precipitation.  See again its all about different combinations but a meaning full combination..:)  You can reverse this technique this way also.

Dissolve your compound in minimum amount of polar solvent and add this to your non-polar solvent slowly under stirring.  And check for precipitations.   This might work in some cases where the other mode of addition hasn’t worked.

Idea 4:  This is exactly a recrystallisation.  Dissolve your compound in a more polar solvent but in minimum volume under heating.  Basically what you do is take your compound and put in some polar solvent say like 5 or 8 volumes roughly.  Then start heating it until it dissolves or sometimes you need reflux for it to dissolve.  Once you get a solution of your compound, cool the solution to rt (or cool sometimes if you don’t see any ppt) and check for precipitation and filter if you get enough time precipitated.

 

Finally any of these techniques may or may not work for you.. Its all about trial and error.  Some times you end up getting oily product.  Don't worry repeat the same technique with few crystals of pure compound and see if it does any good.  Final word of suggestion be careful with hot RC.

NMR Residual Solvent Peaks

Below is the link for residual solvent peaks in 1H NMR and 13C NMR.  I have got this link from Rochester university website.  Thanks to Department of Chemistry, Bar-Ilan University (Israel) for collecting all this data.


Click here to download the pdf copy.

Organic Solvent Properties

Below is the list of solvents along with density, melting point, boiling point, Formula weight.  I have also inlcuded CAS no so that it will be helpful to you during your work.  Please bring to my notice if there is any mistake in this list.:)

Solvent	CAS No	FW	MP	BP	Density
Acetone	67-64-1	58.08	-94	56	0.791
Acetonitrile	75-05-8	41.05	-48	82	0.786
Benzene	71-43-2	78.11	5	80	0.874
Benzonitrile	100-47-0	103.12	-13	188	1.010
1-Butanol	71-36-3	74.12	-90	117.7	0.810
2-Butanone	78-93-3	72.11	-87	80	0.805
Butyl acetate	123-86-4	116.16	-78	124-126	0.882
tert-Butyl methyl ether	1634-04-4	88.15	--	53-56	0.74
Carbon disulfide	75-15-0	76.14	-112	46	1.266
Carbon tetrachloride	56-23-5	153.82	-23	77	1.594
Chlorobenzene	108-90-7	112.56	-45	132	1.107
1-Chlorobutane	109-69-3	92.57	-123	77-78	0.886
Chloroform	67-66-3	119.38	-63	60.5-61.5	1.492
Cyclohexane	110-82-7	84.16	6.5	80.7-81	0.779
Cyclopentane	287-92-3	70.14	-94	50	0.751
1,2-Dichlorobenzene	95-50-1	147	-18 to -15	179-180	1.306
1,2-Dichloroethane	107-06-2	98.96	-35	83	1.256
Dichloromethane	75-09-2	84.93	-97	39.8-40	1.325
N,N-Dimethylacetamide	127-19-5	87.12	-20	164.5-166	0.937
N,N-Dimethylformamide	68-12-2	73.10	-61	153	0.944
1,4-Dioxane	123-91-1	88.11	11.8	100-102	1.034
Ether	60-29-7	74.12	-116	34.6	0.708
2-Ethoxyethyl ether	112-36-7	162.23	--	180-190	0.909
Ethyl acetate	141-78-6	88.11	-84	76.5-77.5	0.902
Ethyl alcohol	64-17-5	46.07	-130	78	0.785
Ethylene glycol dimethyl ether	110-71-4	90.12	-58	85	0.867
Heptane	142-82-5	100.21	-91	98	0.684
Hexane	110-54-3	86.18	-95	69	0.659
Hexanes	73513-42-5	86.18	--	68-69	0.67
2-Methoxyethanol	109-86-4	76.1	-85	124-125	0.965
2-Methoxyethyl acetate	110-49-6	118.13	-65	145	1.009
Methyl alcohol	67-56-1	32.04	-98	64.6	0.791
2-Methylbutane	78-78-4	72.15	--	30	0.62
4-Methyl-2-pentanone	108-10-1	100.16	-80	117-118	0.8
2-Methyl-1-propanol	78-83-1	74.12	-108	108	0.803
2-Methyl-2-propanol	75-65-0	74.12	25	83	0.786
1-Methyl-2-pyrrolidinone	872-50-4	99.13	-24	81-82 (3)	1.033
Methyl sulfoxide	67-68-5	78.13	18.4	189	1.101
Nitromethane	75-52-5	61.04	-29	100.8-101	1.127
1-Octanol	111-87-5	130.23	-15	196	0.827
Pentane	109-66-0	72.15	-130	35-36	0.626
3-Pentanone	96-22-0	86.13	-40	102	0.853
1-Propanol	71-23-8	60.1	-127	97	0.804
2-Propanol	67-63-0	60.1	-89.5	82.4	0.785
Pyridine	110-86-1	79.1	-42	115	0.978
Tetrachloroethylene	127-18-4	165.83	-22	121	1.623
Tetrahyrdofuran	109-99-9	72.11	-108	67	0.886
Toluene	108-88-3	92.14	-93	111	0.867
1,1,2-Trichlorotrifluoroethane	76-13-1	187.38	-35	47-48	1.575
2,2,4-Trimethylpentane	540-84-1	114.23	-107	98-99	0.692
Water	7732-18-5	18.02	0	100	1
o-Xylene	95-47-6	106.17	-25 to -23	143-145	0.870
p-Xylene	106-42-3	106.17	12-13	138	0.866