Solid Derivative Synthesis Procedures
Always make 2 derivatives: one of the authentic compound and one of the unknown.
Reactants must be free of water except as noted – dry them before starting!
Learn and use proper recrystallizing technique, especially with mixed solvents.
Many reagents are hazardous. Make yourself aware of their hazards and of actions you should take if exposed.
Selected SOLID DERIVATIVES for various FUNCTIONAL GROUPS
(protocols appear on subsequent pages)
In your lab notebook be sure to include a reaction and reaction mechanism where
possible for each derivative synthesized.
CAUTION! Before committing to a given derivative, be sure you have its name exactly right. PAY CLOSE ATTENTION
TO SPELLING OF BOTH THE NAME OF YOUR COMPOUND AND THE NAME OF THE DERIVATIVE!! Then
check in the lab reference (at front desk) to see if the melting range for the derivative you have chosen will permit you to
distinguish between candidates for your unknown. Avoid derivatives with low melting ranges and those with high solubility
in water.
Group
Recommended Solid Derivatives
Alcohol
phenylurethane, p-nitrobenzoate or 3,5-dinitrobenzoate
Aldehyde
2,4-DNP-hydrazone or semicarbazone
Alkane
No easy solid derivatives
Alkyl Halide
No easy solid derivatives
Alkene **
oxidative cleavage to RCOOH and/or ketone
Amine
alkyl:
aryl:
Arene
nitro derivatives (only for some)
Aryl Halide
nitro derivatives (only for some)
Carboxylic Acid
amide, anilide, or p-toluidide; neutralization equivalent is also OK for ID-see p. 5
Ketone
2,4-DNP-hydrazone or semicarbazone
Phenol
perbromo derivative, phenylurethane, or 3,5-dinitrobenzoate
benzamide or benzenesulfonamide
those above, plus perbromo derivatives
** Check with instructor before deciding how to proceed.
See USEFUL
PROCEDURAL GOODIES on the next page.
-1-
Solid Derivative Synthesis Procedures
Always make 2 derivatives: one of the authentic compound and one of the unknown.
Reactants must be free of water except as noted – dry them before starting!
Learn and use proper recrystallizing technique, especially with mixed solvents.
Many reagents are hazardous. Make yourself aware of their hazards and of actions you should take if exposed.
USEFUL PROCEDURAL GOODIES
Recrystallization Technique: Work in a beaker. Choose size so that it is ~1/2 to 3/4 full after all solvent has
been added. Keep it covered with a watchglass unless you are actively working inside it. Put your crude solid into the
beaker and dissolve in a suitable solvent as you heat the beaker. Often ethanol is a good choice, but consult the protocol you
are using. Use the smallest volume of solvent that, when at its boiling point, is able to completely dissolve the solid (trial and
error). The key to success is having a hot clear solution that you cool slowly (keeping it covered) so that crystals form
slowly and, in so doing, exclude impurities.
Sometimes there is insoluble matter (does not disappear if you add a little more solvent). Insoluble material needs to
be removed by hot filtration – see below.
After you have a clear, hot solution, you can do a little “quick and dirty” work in a small test tube to speed things
along. Pour about 1 mL of the hot solution into the tube. Swirl the tube vigorously to cool its contents fast (if no crystals
form, cool in ice).
 If crystals do form in the tube, this solvent will work well. Swirl the tube contents, return them to the beaker, and
cover it. Reheat if necessary to get a clear solution, then cool slowly, eventually on ice.
 If no crystals form in the tube, either you have used too much solvent, or this solvent won’t work.
 If water is miscible in the solvent, add water slowly with mixing to see if the mixture becomes cloudy. If it
becomes cloudy, stir and scratch gently to see if crystals will form. If they do, note the approximate percent
incease in volume due to added water. Return the tube contents to the beaker, add the appropriate amount of
water, cover, reheat as needed to get a clear solution, and cool as above.
 If adding water doesn’t help, or if water is not compatible with the major solvent, you’ll need to boil off at least
half of the solvent. Return the contents of the tube to the beaker, boil it down, and then start again at the top of
this paragraph.
 Instructors may be able to help in hard cases.
Filter crystals on a Hirsch funnel and let air-dry for at least a day before taking a melting point.
HOT FILTRATION (to remove insoluble material from a recrystallization in progress)
Pour in hot
suspension
Assemble the apparatus shown using a 400 ml beaker and
stemless funnel.
Fold the largest piece of filter paper you can find into a
cone and put into funnel. Cover with watchglass.
Bring beaker solvent to a slow boil and allow vapors to
heat up all glassware.
Heat suspension you wish to filter, then pour as much as
possible into funnel.
Cover and continue to boil very gently (don't let it go dry!).
Desired material is in filtrate.
Keep
covered
with
watch
glass!
Hot Plate
-2-
Boiling
solvent
(thin
layer)
Solid Derivative Synthesis Procedures
Always make 2 derivatives: one of the authentic compound and one of the unknown.
Reactants must be free of water except as noted – dry them before starting!
Learn and use proper recrystallizing technique, especially with mixed solvents.
Many reagents are hazardous. Make yourself aware of their hazards and of actions you should take if exposed.
ALCOHOLS
Phenylurethane – work in a hood
In a 20 mL beaker, mix 0.5 mL (4.60 mmols) phenylisocyanate (lachrymator!!  USE HOOD!!) with 5.52 mmols
of an alcohol (must be anhydrous). Mixture may spontaneously get hot. If not, warm it at a low setting until it does get
hot (watch carefully – only a little vapor – “steam” - will be evident). You may need to feel it cautiously. Once hot,
remove to desk top inside hood. While reaction mixture cools to room temperature, use a stirring rod to mix and loosen
the solid as it forms.
Vacuum filter the solid and recrystallize it from warm petroleum ether or hexanes (keep beaker covered!!). There
will probably be a significant amount of white solid that does not dissolve even when solvent boils. This must be
removed by hot filtration (or, it may settle so that you can just pour off the clear liquid). Allow the clear solution
(covered!) to cool. Scratching may be necessary to get crystals.
3,5-dinitrobenzoate or 4-nitrobenzoate ester: work in hood; choose the one that gives the derivative with the highest m.p.
Weigh approximately 0.5 g of 3,5-dinitrobenzoyl chloride [FW = 231] or 0.4 g of 4-nitrobenzoyl chloride [FW =
186] into a tiny beaker. Compute the moles of reagent based on its measured mass and multiply the result by 1.5.
Compute the mass of your alcohol that corresponds to this number of moles and weigh at least this much into the beaker.
Heat at a low setting until fumes evolve (hood!) – but avoid heating so hot that color changes. Keep warm for ~10
min. Cool to room temperature.
Add 10 mL of 0.2 M Na2CO3 and mix well until everything is solid (this base destroys excess acyl chloride and
ionizes resulting substituted benzoic acid so that it can be removed by the water wash). Crush any large chunks of solid
to permit maximum contact with the base. Filter (Hirsch!) and wash the solid with water. Recrystallize from 10 mL of
warm EtOH (covered!). If no crystals return on cooling, reheat and add water to the cloud point as you keep it warm,
then allowing to cool slowly (covered).
ALDEHYDES
2,4-dinitrophenylhydrazone
Work in a small beaker. Follow instructions for the corresponding ID test (use the precipitate as your derivative). If
this did not give enough precipitate, you can increase the amount of aldehyde a little (don’t add too much because the
aldehyde is a good solvent for the desired derivative, and you may not get any crystals). Mix thoroughly with a stirring
rod. Filter the precipitate after letting the reaction go for about 3 min. Wash while on the filter with about a mL of icecold EtOH. Suspend the solid in 5 mL of 5 % NaHCO3 and break up the crystals to ensure good mixing with the
NaHCO3 (this step removes DNP reagent and sulfuric acid from the solid and is essential to obtaining good crystals).
Filter the solid and recrystallize from about 30 mL of EtOH. (When hot, the mixture will likely be very dark, which
makes it hard to see whether all solids are in solution, so observe carefully. If difficult to dissolve, you can add up to 1
mL of ethyl acetate.) If crystals do not re-form when at room temperature, add water slowly with good mixing just until
cloudy, cover, reheat until clear (but still colored!), and cool slowly.
Semicarbazone – work in a hood
Dissolve 0.5 g of semicarbazide hydrochloride in 2 mL of water. In a separate tube that contains 2 mL of MeOH,
dissolve 4 millimoles of the aldehyde. Pour the clear solution into the semicarbazide solution and add 0.5 mL of pyridine
(STENCH!). Mix well. Warm gently for 5 minutes, then allow to cool. Crystals should form (scratch?). Cool on ice,
recover crystals, and wash with water followed by a little ice-cold MeOH. Recrystallize from MeOH, EtOH, or
EtOH/water.
ALIPHATIC AND AROMATIC HYDROCARBONS AND HALIDES
No easy solid derivatives of these classes are possible. For some aromatics, exhaustive nitration can work. Check
with instructor.
ALKENES
These can be difficult. Certain alkenes can be oxidatively cleaved to make solid carboxylic acids. Consult with
instructor.
-3-
Solid Derivative Synthesis Procedures
Always make 2 derivatives: one of the authentic compound and one of the unknown.
Reactants must be free of water except as noted – dry them before starting!
Learn and use proper recrystallizing technique, especially with mixed solvents.
Many reagents are hazardous. Make yourself aware of their hazards and of actions you should take if exposed.
ALKYL HALIDES
No easy solid derivatives of these classes are possible. Check with instructor.
AMINES (1° and 2° only)
If dark colored, try to decolorize with charcoal before making derivative – see instructor.
Benzamides (OK for all amines) – work in a hood
Work in a small Erlenmeyer flask that contains a small stir bar. Mix 0.5 g of benzoyl chloride (lachrymator;
cautiously note its odor) with 0.5 g of amine. Stir vigorously while you add 2 mL of 3 M NaOH. Monitor pH with litmus
paper. Add more portions of NaOH as needed to keep pH alkaline. Reaction is over when odor of benzoyl chloride is
gone and no more oil is visible. Recover solid, wash with water. Recrystallize from water or ethanol/water.
Acetamides (NOT suitable for small amines. See instructor if you have a weakly basic amine – long reflux and
pyridine are necessary.)
Reflux 1 g of amine with 0.5 mL of acetic anhydride for 5 min. Cool, then dilute with 5 mL of water. Scratch if
necessary to induce crystallization. (If any oily material is visible, some unreacted acetic anhydride is left, and this must
be allowed to hydrolyze before you proceed. Crude product must be a free-flowing solid.) Recover crystals and wash
with a little 1 M HCl to remove any unreacted amine. Recrystallize from water or ethanol/water.
Benzenesulfonamides – check to verify that the anticipated derivative melts above 60 °C. If it does, use the procedure for the
Hinsberg Test in the ID Tests document.
Perbromo derivative: follow procedure under Phenols
CARBOXYLIC ACIDS
Amides (NOT suitable for small acids; check with instructor before choosing)
Work in your hood – this procedure releases HCl and SO2 gases. Reflux 1 g of carboxylic acid with 2 mL of thionyl
chloride for 30 min (the mole ratio of SOCl2:carbox. acid should be about 1.5:1). In the hood, in an Erlenmeyer flask on
ice containing a stir bar, chill 20 mL of concentrated ammonia (ammonium hydroxide). When reflux is finished, cool the
boiling flask without disassembling. Once cool, remove all glassware and use a Pasteur pipet to cautiously transfer the
reaction mixture to the flask in ice that contains ammonia (stirring!). Each drop will hiss, spatter and produce lots of
white smoke. When addition is complete, recover the solid and recrystallize from water (frequently a good choice!) or
ethanol/water.
Anilides or p-Toluidides (OK for any acid, but generates a lot of waste and product is challenging to recover from
reaction solvent)
Work in your hood – this procedure releases HCl and SO2 gases. Reflux 1 g of carboxylic acid with 2 mL of thionyl
chloride for 30 min (the mole ratio of SOCl2:carbox. acid should be about 1.5:1). While this is going on, prepare the
amine that you chose, keeping in mind that it is toxic and easily absorbed through the skin. Working in a small
Erlenmeyer flask that contains a stir bar, dissolve 2.5 g of aniline (avoid really dark stuff) or p-toluidine in 10 mL of
toluene. Cool this on ice. After reflux is finished, lower the heating mantle and allow to cool before disassembling.
When cool, remove glassware and use a Pasteur pipet to cautiously transfer the reaction mixture to the stirred flask
in ice. Lots of heavy precipitate will form, but you do not want it. The product you want remains soluble in the toluene.
Remove the solids by filtration, and wash them with a little clean toluene. Pour the combined toluene filtrates into a
separatory funnel and shake in sequence with water, HCl (1 – 3 M), NaOH (1 – 3 M), and water. This treatment removes
unreacted carboxylic acid and unreacted amine. Dry the washed toluene solution over CaCl 2, then remove solvent (distill
without overheating the residue, or evaporate under vacuum). Recrystallize residue from ethanol/water or water.
The waste solids filtered off earlier are toxic – ask the instructor what you should do with them.
-4-
Solid Derivative Synthesis Procedures
Always make 2 derivatives: one of the authentic compound and one of the unknown.
Reactants must be free of water except as noted – dry them before starting!
Learn and use proper recrystallizing technique, especially with mixed solvents.
Many reagents are hazardous. Make yourself aware of their hazards and of actions you should take if exposed.
Equivalent weight: How to estimate the equivalent weight of an unknown carboxylic acid by titration
This is not a solid derivative, but for the purposes of this course is an acceptable alternate way to establish identity of a
carboxylic acid.
1. Obtain (or make) 300 mL of approximately 0.1 M NaOH. This concentration will allow you to use about 30 mL for
each titration. Titration can be done using a pH meter (recommended because you can see the end point coming; use a
beaker) or an indicator like phenolphthalein (in which case, use Erlenmeyer flasks and do the titration on a white
surface). A magnetic stirrer helps with either method.
2. Standardize the NaOH: Use potassium hydrogen phthalate (KHP; also called potassium biphthalate). The formula
weight of KHP is 204.2212 g/mol. Weigh three samples of KHP, each containing about 0.003 mole, into separate
containers. Double check your calculation and record the actual masses used! Dissolve each in convenient amounts of
water (the volume does not matter). Titrate each to pH ~8.5 using your NaOH. If any liquid splashes onto the side of
the flask you must rinse it down using your wash bottle. Use the moles of KHP and the volume of NaOH consumed to
calculate the (average) actual concentration of the NaOH.
3. Titrate unknown acid: You should have a pretty good idea of the identity of the acid. Calculate the mass of it that
should contain about 0.003 mole of H+ (again, double-check your figures). Weigh three samples of the acid (even if a
liquid), dissolve each in about 20 mL of water (or ethanol if not soluble in water), and titrate as above. From the
volume of NaOH used and its known concentration you can calculate the number of "equivalents" of acid present in
each sample (one equivalent = one mole of H+). Use these and the corresponding masses of unknown to compute the
average equivalent weight (the mass of acid that contains one mole of acidic H atoms).
ESTERS
These must be hydrolyzed into their constituent carboxylic acid and alcohol. The products must be separated and
isolated, then individually characterized. If you were given an ester, you will not have a second component in your
unknown.
Hydrolysis: In a 50 mL boiling flask, add 0.310 mol of NaOH pellets, 10 mL of the ester, and 15 mL water. Reflux
this mixture with good mixing for 1 hr buried in a sand bath. The resulting reaction mixture will contain the neutral
alcohol and the anion of the carboxylic acid. It is up to you to figure out how to physically separate, recover, and identify
each of these compounds. Remember that either or both of the components of the ester may be water-soluble.
KETONES: follow either procedure under ALDEHYDES
PHENOLS
if dark-colored, try to decolorize with charcoal before making derivative – see instructor
Perbromo derivative – work in a hood
Caution: chemical burn hazard! Have at hand a bottle of aq. sodium bisulfite (spelling!!), sodium thiosulfate, or
glycerol. If you get any Br2 on you, rub one of these substances into the affected area, then rinse with water. The
chemicals will neutralize the Br2.
Find the bottle of Br2 in water; make sure you can see some very dark elemental Br2 at the bottom. If it is not full of
water, open it in the hood (Br2 vapor will escape) and add water, then cap tightly and shake for a minute to saturate the
water with Br2. Take this to your desk hood.
Work in a 250 mL beaker that contains a stir bar. Dissolve about 0.25 g of phenol in a little methanol. As you stir,
slowly add Br2/H2O at such a rate that the color disappears almost instantly. Make sure that you add only the clear redbrown water solution of Br2 , not the very dark elemental Br2 . Eventually a white solid will form. Keep adding Br 2
slowly until significant color persists for several minutes. Heat the covered mixture gently for a few minutes to insure
that the Br2 color persists. After you are sure that no more Br2 is reacting, add an aqueous solution of sodium hydrogen
sulfite (NaHSO3; also called bisulfite; note spelling and formula) a little at a time until the color vanishes. Recover the
solid, wash with water while on the funnel, and recrystallize from ethanol/water (if you don’t know this technique, ask
for help).
Phenylurethane: follow procedure under ALCOHOLS
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