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Author: Subject: Volunteer project: Org. chem. index of amateur syntheses
Nicodem
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[*] posted on 30-10-2013 at 12:41
Volunteer project: Org. chem. index of amateur syntheses


In order to promote organic synthesis on the forum, I thought to create a sticky thread with an index of suggestions for synthesis practice for those interested. During the years here I noticed only few questions of the "what can I do with compound X", but I believe this ought to be a more common question. I don't have the time to do all the work and therefore I call for collaboration. I need volunteers to post information to add. The response will also be indicative of how much interest there is for such a project.

The idea is to make an index of syntheses that can be done by using simple to acquire compounds (the so called OTC products). The first thing where help is needed is the information on which such compounds are, and where they are available. The second thing is to gather suggestions on what can be done from these compounds in one synthetic step or at least a one-pot step. Thirdly, a short review with references to procedures needs to be added to each suggested synthesis (no more than a few sentences: short reaction description, complexity, cautions, unreferenced suggested further use in synthesis...). Preference should be given to references to this or other amateur chemical forums (Versuchschemie, Hyperlab, etc.), Organic synthesis, Vogel's and other practical org. chemistry manuals, Synthetic Pages, reliable primary literature, open access journals, and such. Obviously, I'm open also to ideas about other types of organisational structures.

Volunteers can post replies with such short reviews on any individual synthesis and these will be later included in the index.

If this becomes a successful project we could do something similar for inorganic syntheses, isolation of compounds from biological materials, educational chemical demonstrations, analytical methods, etc.

Below is a draft, with a few short reviews for syntheses starting with acetone set as examples. Some links are added in order to aid the volunteers. (Formatting and alphabetical order will be done last.)


*************************************************************************************



<a href="#aceticacid">acetic acid</a>

<a href="#acetone">acetone</a>
    <a href="#acetoneazine">acetone azine</a> (N2H4.H2O)
    <a href="#acetonecyanohydrin">acetone cyanohydrin</a> (NaCN, H2SO4)
    <a href="#acetoxime">acetoxime</a> (NaNO2, NaHSO3)
    <a href="#acetylacetone">acetylacetone</a> (Ac2O, AlCl3)
    <a href="#cianopropilhydraz">2,2'-hydrazine-1,2-diylbis(2-methylpropanenitrile)</a> (N2H4.H2SO4, NaCN)
    <a href="#mesitylene">mesitylene</a> (H2SO4)
    <a href="#acetonetms">acetone trimethylsilyl enol ether</a> (TMSCl, NaI, Et3N, MeCN)
    <a href="#chelidonicacid">chelidonic acid</a> (diethyl oxalate, NaOEt, EtOH, HCl)
    <a href="#chloroacetone">chloroacetone</a> (TCCA, H2SO4)
    <a href="#chloroform">chloroform</a> (NaOCl, NaOH)
    <a href="#bromoform">bromoform</a> (Br2, NaOH)
    <a href="#iodoform">iodoform</a> (I2, NaOH)
    <a href="#bromoacetone">bromoacetone</a> (Br2, AcOH)
    <a href="#aminobutanone">4-diethylamino-2-butanone</a> (Et2NH, CH2O, MeOH, HCl)
    <a href="#isopropylidenemalonate">diethyl isopropylidenemalonate</a> (diethyl malonate, ZnCl2, Ac2O)
    <a href="#ketene">ketene</a> (thermolysis)
    <a href="#pinacol">pinacol hydrate</a> (Mg, HgCl2 or I2)
    <a href="#phorone">phorone</a>
    <a href="#diacetone">diacetone alcohol</a> (Ba(OH)2 or Ca(OH)2)
    <a href="#mesityl">mesityl oxide</a> (HCl)
    <a href="#acetonephenylhydrazone">acetone phenylhydrazone</a> (PhNHNH2)
    <a href="#triacetoneamine">triacetone amine</a> (NH3)
    <a href="#triacetylbenzene">1,3,5-triacetylbenzene</a> (HCOOEt, NaOEt, Et2O, AcOH)

acetonitrile
    acetic acid
    acetamide
    N-t-butyl-acetamide

<a href="#aspirin">aspirin (acetyl salicylic acid)</a>
    <a href="#cuasa">copper(II) aspirinate</a>
    <a href="#sa">salicylic acid</a> (H2O)
    <a href="#mesa">methyl salicylate</a> (MeOH, H2SO4)

anethole
    anethole trithione
    anethole oxide
    anethole pseudonitrosite
    anisic acid
    anisaldehyde
    dibromoanethole
    tribromoanethole
    p-methoxyphenylacetone

benzaldehyde

benzoic acid (sodium salt)

2-butanone (MEK)
    propanoic acid
    3-(hydroxyimino)butan-2-one

camphor
    borneol
    camphoric acid

carbon
    carbon disulfide

carbon dioxide
    methyl carbonate salts

cinnamaldehyde
    cinnamic acid
    cinnamyl alcohol
    propenylbenzene (N2H4, KOH)

citric acid

cyanuric acid
    N,N',N"-trimethylisocyanuric acid
    N,N',N"-tris(hydroxymethyl)isocyanuric acid

cellulose
    cellulose acetate
    nitrocellulose

dichloromethane
    diodomethane (NaI, Me2CO)


<a href="#ethanol">ethanol</a>
    acetic acid
    acetaldehyde
    <a href="#et2o">diethyl ether</a> (H2SO4)
    <a href="#etbr">ethyl bromide</a>
    <a href="#etoso3h">ethyl sulfuric acid (and its salts)</a> (NaHSO4)
    sodium ethoxide (NaOH)

ethyl acetate

ethylene glycol

eugenol
    isoeugenol
    O-acetyl eugenol
    O-benzylisoeugenol
    O-methyleugenol
    5-formyleugenol

p-dichlorobenzene
    2,5-dichloronitrobenzene

dimethylsulfoxide
    <a href="#me3sbr">trimethylsulfonium bromide</a> (Br2, Me2CO)
    trimethylsulfoxonium iodide

glucose

glycerol

glyoxal

L-glutamic acid (monosodium salt)

hexamine
    methylamine hydrochloride
    dimethylamine hydrochloride

hydroquinone
    p-benzoquinone
    p-dimethoxybenzene
    p-methoxyphenol

ibuprofen
    ibuprofen, methyl ester

formaldehyde

formic acid
    formamide (NH3)
    ethyl formate
    methyl formate

limonene
    cymene

mannitol

methanol


<a href="#mtbe">methyl t-butyl ether</a>
    <a href="#tbuoh">t-butyl alcohol</a>
    <a href="#tbucl">t-butyl chloride</a>
    isobutene

N-methylpyrrolidin-2-one (NMP)
    N-methyl-gamma-aminobutyric acid

naphthalene
    1-chloromethylnaphthalene
    1-bromonaphthalene
    1-nitronaphthalene
    naphthalene-2-sulfonic acid

naproxen
    naproxen methyl ester

nicotinamide

nicotinic acid

nitromethane
    2-nitroethanol
    hydroxylamine hydrochloride

xylenes
oxalic acid
paraformaldehyde

<a href="#paracetamol">paracetamol (p-hydroxyacetanilide)</a>
    <a href="#aminophenol">p-aminophenol</a>
    <a href="#benzoquinone">p-benzoquinone</a>
    <a href="#meoacetanilide">p-methoxyacetanilide</a>
    <a href="#ohno2acetanilide">4-hydroxy-2-nitroacetanilide</a>


alpha-pinene

beta-pinene

2-propanol
    isopropyl bromide
    isopropyl iodide


propene

propylene glycol
    1,2-propylene carbonate

polyethylene terephthalate


<a href="#salicylic">salicylic acid</a>
    <a href="#aurintricarboxylic">aurin tricarboxylic acid (ammonium salt)</a> (H2SO4, NaNO2, HCHO, NH3)
    <a href="#methylenesalicylic">3,3'-Dicarboxy-4,4'-dihydroxydiphenylmethane</a> (HCHO, HCl)
    <a href="#nitrosalicylic">5-nitrosalicylic acid</a> (HNO3, AcOH)
    <a href="#dibromosalicylic">3,5-dibromosalicylic acid</a> (Br2, AcOH)
    <a href="#tribromophenol">2,4,6-tribromophenol</a> (Br2)
    <a href="#parabenic">p-hydroxybenzoic acid</a> (K2CO3)
    5-sulfosalicylic acid https://www.sciencemadness.org/whisper/viewthread.php?tid=24...
    3- and 5-formylsalicylic acid (hexamine, AcOH, H2SO4)
    <a href="#phenol">phenol</a>
    picric acid
    <a href="#salicylamide">salicylamide</a> (urea, H3PO4)

sodium benzoate
    benzoic acid

sucrose

starch

<a href="#styrene">styrene</a>


<a href="#tartaric">tartaric acid</a>
    diethyl tartrate
    dibutyl tartrate
    <a href="#pyruvic">pyruvic acid</a> (KHSO4)


tetrachloroethene

tetrahydrofuran
    1,4-dibromobutane (HBr)
    4-chlorobutyl acetate (AcCl, ZnCl2)

toluene

trichloroisocyanuric acid
    cyanuric acid

trichloroethene
    chloroacetic acid

thiourea

urea

vanillin




---------------------------------------------------------------------------------

<h1><a id="acetone" href="#acetone"></a>Acetone</h1>
A common solvent that can easily be aquired in hardware shops. Its main modes of reactivity are the nucleophilic additions to its double bond, the reaction of electrophiles with the acetone derived enolate, and electrophilic addition on the double bond of the enol tautomer.

<h2><a id="acetoneazine" href="#acetoneazine"></a>Acetone azine</h2>
The double condensation of acetone to hydrazine hydrate gives acetone azine.1 Hydrazine hydrate is toxic and carcinogenic and must be used only in a fume hood and treated with caution.
1. Org. Synth. http://www.orgsyn.org/demo.aspx?prep=cv6p0010

<h2><a id="acetonecyanohydrin" href="#acetonecyanohydrin"></a>Acetone cyanohydrin </h2>
The nucleophilic addition of HCN to acetone gives acetone cyanohydrin.1 CAUTION: This synthesis requires a fume hood and is extremely hazardous with the reagents and the product being highly toxic.
1. Org. Synth. http://www.orgsyn.org/demo.aspx?prep=cv2p0007

<h2><a id="acetoxime" href="#acetoxime"></a>Acetoxime </h2>
Acetoxime can be prepared either directly by the condensation of acetone with hydroxylamine1 or indirectly by the reaction with the HON(SO3Na)2 salt prepared in situ from NaNO2 and NaHSO3.2
1.
2. Org. Synth. http://www.orgsyn.org/demo.aspx?prep=cv1p0318

<h2><a id="acetylacetone" href="#acetylacetone"></a>Acetylacetone</h2>
C-Acylation of acetone gives acetylacetone. This is generally Lewis acid catalysed (BF3, AlCl3, etc.) and uses acetic anhydride.1 Acetylacetone is an excellent starting material for the synthesis of certain heterocycles (3,5-dimethylpyrrazole, 3,5-dimethylisoxazole, pyrimidines), can be oxidized to tetraacetylethane or be C-alkylated or C-arylated to numerous products.
1. http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv3...
<h2><a id="acetonephenylhydrazone" href="#acetonephenylhydrazone"></a>Acetone phenylhydrazone</h2>
This hydrazone is an intermediate in the synthesis of 2-methylindole by the Fischer indole synthesis.1
1. Fischer, Ann., 236, 116 (1886); Ber., 19, 1563 (1886); Marion and Oldfield, Can. J. Research, 25B, 1 (1947).
<h2><a id="cianopropilhydraz " href="#cianopropilhydraz "></a>2,2'-Hydrazine-1,2-diylbis(2-methylpropanenitrile) </h2>
https://www.sciencemadness.org/whisper/viewthread.php?tid=10...
<h2><a id="chloroform" href="#chloroform"></a>Chloroform</h2>
<h2><a id="bromoform" href="#bromoform"></a>Bromoform</h2>
<h2><a id="iodoform" href="#iodoform"></a>Iodoform</h2>
<h2><a id="mesitylene" href="#mesitylene"></a>Mesitylene </h2>
Mesitylene is the product of the acid catalyzed triple selfcondensation of acetone.1 This reaction is an interesting demonstration of building up an aromatic system from a nonaromatic compound. Mesitylene can be further functionalized by electrophilic aromatic substitutions or it can be oxidized to trimesic acid.
1. http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv1...
<h2><a id="acetonetms" href="#acetonetms"></a>Acetone trimethylsilyl enol ether </h2>
The O-silylation of acetone with Me3SiCl gives acetone trimethylsilyl enol ether,[1] a useful acetone synthone that can be C-functionalized with some electrophilic reagents.
1. http://www.orgsyn.org/demo.aspx?prep=cv8p0001
<h2><a id="chelidonicacid" href="#chelidonicacid"></a>Chelidonic acid </h2>
The double condensation of diethyl oxalate with acetone and the consequent cyclisation gives chelidonic acid.1 This is an interesting example of heterocyclic cyclocondensation chemistry, yielding a substituted 4-pyranone.
1. http://www.orgsyn.org/demo.aspx?prep=cv2p0126
<h2><a id="chloroacetone" href="#chloroacetone"></a>Chloroacetone</h2>
Electrophilic monochlorination of acetone yields chloroacetone. Chlorine or other electrophilic chlorinating reagents can be used. Of these, the most practical is trichloroisocyanuric acid where a tiny amount of H2SO4 is used for acidic catalysis.[1] This synthesis is very exothermic. For this reason it should never be upscaled or modified in any way (particularly the amount of the H2SO4 should never be increased – dangerous runaways have been reported due to thoughtless modifications!). CAUTION: Chloroacetone is a very potent lachrymator and is potentially genotoxic. Its synthesis and distillation should only be carried in a fume hood and all the used equipment quenched with ammonia.
1. Patent application FR2633614
<h2><a id="bromoacetone" href="#bromoacetone"></a>Bromoacetone</h2>
Bromoacetone can be prepared, analogously to chloroacetone, by the electrophilic bromination of acetone. Bromination with elemental bromine in acetic acid can be applied.1 CAUTION: Bromoacetone is a very potent lachrymator and is potentially genotoxic. Its synthesis and distillation should only be carried in a fume hood and all the used equipment quenched with ammonia.
[1] http://www.orgsyn.org/demo.aspx?prep=cv2p0088
<h2><a id="aminobutanone" href="#aminobutanone"></a>4-Diethylamino-2-butanone </h2>
Acetone can be a substrate for the Manich condensations. One such is the reaction with diethylamine and formaldehyde,1 but other secondary amines can also be used to give the corresponding 4-dialkylamino-2-butanones.
1. http://www.orgsyn.org/demo.aspx?prep=cv4p0281
<h2><a id="isopropylidenemalonate" href="#isopropylidenemalonate"></a>Diethyl isopropylidenemalonate</h2>
Acetone can undergo Knoevenagel condensations with some reagents containing a reactive methylene group. One such example is the condensation of acetone with diethyl malonate.[1]
1. http://www.orgsyn.org/demo.aspx?prep=cv6p0442
<h2><a id="#ketene" href="#ketene"></a>Ketene</h2>
Thermolysis of acetone gives ketene and methane.[1] CAUTION: Ketene is very toxic and reactive. It should be quenched, dimerized or consumed in a reaction immediately after formation. Its handling requires proper equipment and should only be done by very experienced chemists.
1. http://www.orgsyn.org/demo.aspx?prep=cv1p0330
<h2><a id="pinacol" href="#pinacol"></a>Pinacol hydrate</h2>
Reduction of acetone with activated magnesium in anhydrous media gives pinacol (pinacol coupling).[1]
1. http://www.orgsyn.org/demo.aspx?prep=cv1p0459
<h2><a id="phorone" href="#phorone"></a>Phorone</h2>
<h2><a id="diacetone" href="#diacetone"></a>Diacetone alcohol</h2>
1. http://www.orgsyn.org/demo.aspx?prep=CV1P0199
<h2><a id="mesityl" href="#mesityl"></a>Mesityl oxide</h2>
1. ref 1 in http://www.orgsyn.org/demo.aspx?prep=cv1p0345
<h2><a id="triacetoneamine" href="#triacetoneamine"></a>Triacetone amine</h2>
https://www.sciencemadness.org/whisper/viewthread.php?tid=26...
<h2><a id="triacetylbenzene" href="#triacetylbenzene"></a>1,3,5-Triacetylbenzene</h2>
1. http://www.orgsyn.org/demo.aspx?prep=cv3p0829

<h1><a id="aspirin" href="#aspirin"></a>Aspirin (acetyl salicylic acid)</h1>
Aspirin or acetyl salicylic acid is an active pharmaceutical ingredient that is inexpensive and sold in large dosage forms (e.g., 0.5 g tablets, commonly with only very small amounts of binders and other excipients, if at all).

<h2><a id="cuasa" href="#cuasa"></a>Copper(II) aspirinate</h2>
Aspirin forms a carboxylate complex with Cu(II).1
1. SM: Copper(II) Aspirinate Synthesis
<h2><a id="sa" href="#sa"></a>Salicylic acid</h2>
<h2><a id="mesa" href="#mesa"></a>Methyl salicylate</h2>

<h1><a id="dmso" href="#dmso"></a>Dimethyl sulfoxide (DMSO)</h1>
DMSO is a common polar aprotic solvent that is sometimes easily available to the public.

<h2><a id="me3sbr" href="#me3sbr"></a>Trimethylsulfonium bromide</h2>

The reaction of bromine with dimethylsulfoxide (DMSO) first starts with the rapid and highly exothermic S-bromination, but the initial product goes trough a complex series of much slower decompositions and further reactions, until at the end the major product is the trimethylsulfonium bromide. This can easily be isolated by precipitation with acetone and filtration. The product can be used as an electrophilic methylation reagent. CAUTION: Bromine is very hazardous, volatile and corrosive liquid. Its reaction with DMSO is very violent. Dangerous splattering can occur!
1. SM: Trimethylsulfonium bromide and its use for the methylation of phenols

<h1><a id="mtbe" href="#mtbe"></a>Methyl t-butyl ether (MTBE)</h1>
<h2><a id="tbuoh" href="#tbuoh"></a>tert-Butyl alcohol</h2>
MTBE can be cleaved directly to a mixture of methanol, tert-butyl alcohol and isobutene by dilute aq. non-nucleophilic acid catalysis (e.g., H2SO4, NaHSO4, etc.).1
1.

<h2><a id="tbucl" href="#tbucl"></a>tert-Butyl chloride</h2>
The SN1 substitution at MTBE with concentrated aqueous HCl easily gives tert-butyl chloride by the cleavage of methanol.1 The crude product can be isolated by phase separation.
1. SM: tert-Butyl Alcohol


<h1><a id="ethanol" href="#ethanol"></a>Ethanol</h1>
Ethanol is a common solvent that can be acquired in hardware shops or pharmacies. It can also be isolated by distillation from brandy or other alcoholic beverages.

<h2><a id="etbr" href="#etbr"></a>Ethyl bromide</h2>
Ethyl bromide is most easily prepared by its reaction with hydrobromic acid. The product is distilled from the reaction mixture.1 Instead of the 48% hydrobromic acid, it is also possible to use suitable bromide salts (NaBr, KBr, NH4Br, etc.) in combination with sulfuric acid.2
1. Org. Synth. 1921, 1, 3.
2. SM: Ethyl/Isopropyl Bromide preparation

<h2><a id="et2o" href="#et2o"></a>Diethyl ether</h2>
Ethanol can be self-condensed to diethyl ether. The reaction is generally catalysed by sulfuric acid and needs to be conducted at about 140 °C in order for diethyl ether to be the main product.
1. SM: Diethyl Ether - Illustrated Practical Guide

<h2><a id="etoso3h" href="#etoso3h"></a>Ethyl sulfuric acid (and its salts)</h2>
The esterification of ethanol with sulfuric acid gives ethyl sulfuric acid (EtOSO3H). Different methods exist for the esterification. Already the reaction of sulfuric acid with anhydrous ethanol gives a moderate yield of ethyl sulfuric acid. Formation of the soluble calcium or barium salt is necessary in order to remove the residual sulfuric acid as the insoluble sulfates.1 The calcium or barium salts can then be transformed to soluble sodium or potassium ethyl sulfates by ion metathesis employing Na2CO3 or K2CO3. The complete esterification is possible by either employing anhydrous NaHSO4,2 or sulfuric acid with anhydrous Na2SO4.3
1. SM: Nitroethane from ethylsulfate, Desseigne variation.
2. Patent application US3024263
3. SM: Sodium Ethyl Sulfate

<h1><a id="salicylic" href="#salicylic"></a>Salicylic acid</h1>
Salicylic acid is often available through various sources, including internet auction sites. Alternatively, it is very easily prepared by the facile hydrolysis of aspirin.1
1. SM: Preparation of Phenol from Salicylic Acid

<h2><a id="aurintricarboxylic" href="#aurintricarboxylic"></a>Aurin tricarboxylic acid (ammonium salt)</h2>
The acid catalysed oxidative triple condensation of salicylic acid with formaldehyde gives aurin tricarboxylic acid.1 This compound has a variety of biological activities.2 Its ammonium salt is a reagent for the colorimetric estimation of aluminum.3
1. http://www.orgsyn.org/demo.aspx?prep=CV1P0054
2.
3. J. Am. Chem. Soc., 1925, 47, 142–143. DOI: 10.1021/ja01678a019

<h2><a id="methylenesalicylic" href="#methylenesalicylic"></a>3,3'-Dicarboxy-4,4'-dihydroxydiphenylmethane</h2>

<h2><a id="parabenic" href="#parabenic"></a>para-Hydroxybenzoic acid</h2>
The reversibility of the Kolbe-Schmitt reaction can be used to rearrange salicylic acid to the thermodinamically more stable p-hydroxybenzoic acid. This is achieved by heating the potassium salt of salicylic acid at 240 °C.1 The salt is prepared using K2CO3 and after the reaction the product is liberated from its double potassium salt with HCl(aq). One half of the salicylic acid is decarboxylated to phenol, which distils out of the reaction mixture and should be recovered with a condenser. As such, the reaction can be used to prepare two products, p-hydroxybenzoic acid and phenol, with good yields. The p-hydroxybenzoic acid can be used to prepare alkyl parabens. It can also serve as a substrate for various electrophilic aromatic substitutions. CAUTION: Phenol is moderately toxic and its fumes should be either condensed or the reaction conducted in a fume hood.
1. Organic Syntheses, 1934, 14, 48.

<h2><a id="dibromosalicylic" href="#dibromosalicylic"></a>3,5-Dibromosalicylic acid</h2>
The dibromination of salicylic acid quite selectively gives the 3,5-dibromosalicylic acid. This can be achieved with near quantitative yields by various bromination methods. The most elementary is the reaction with bromine in acetic acid.1
1. Russian Journal of General Chemistry, 2004, 74, 738-743. DOI: 10.1023/B:RUGC.0000039088.87053.eb

<h2><a id="tribromophenol" href="#tribromophenol"></a>2,4,6-Tribromophenol</h2>
The electrophilic tribromination of salicylic acid with bromine is accompanied by decarboxylation and gives 2,4,6-tribromophenol in nearly quantitative yields.1 CAUTION: Halophenols in general are toxic and have an unpleasant and difficult to remove stench.
1. J. Am. Chem. Soc., 1924, 46, 2498–2505. DOI: 10.1021/ja01676a020

<h2><a id="nitrosalicylic" href="#nitrosalicylic"></a>5-Nitrosalicylic acid</h2>
Electrophilic mononitration of salicylic acid under relatively mild conditions gives predominantly the 5-nitro isomer. Various procedures can be found in the literature, of which the nitration with 65% HNO3(aq) in acetic acid as the solvent appears the most straightforward.1 The nitration is also possible with a nitric and sulfuric acid mixture.2 Yields are commonly moderate, often due to the unselectivity and consequent recrystallization losses. 5-Nitrosalicylic acid can be reduced to 5-aminosalicylic acid. The regioisomeric 3-nitrosalicylic acid can be prepared by employing a more ortho-selective reagent.3
1. J. Chem. Soc., 1946, 965-967. DOI: 10.1039/JR9460000965; see also Org. Process Res. Dev., 2008, 12, 995–1000. DOI: 10.1021/op800112u
2. J. Prakt. Chem., 1890, 42, 550–553. DOI: 10.1002/prac.18900420150
3. Synth. Commun., 2010, 40, 3353-3357. DOI: 10.1080/00397910903419852; Patent application GB2377934.

<h2><a id="phenol" href="#phenol"></a>Phenol</h2>

Thermal decarboxylation of salicylic acid at about 180 °C gives phenol in moderate to good yields.1 Bases, such as K2CO3 or Ca(OH)2, catalyse the decarboxylation via the retro-Kolbe-Schmitt reaction mechanism so that the reaction can proceed with better efficiency even at the lower temperatures (~140 °C).2
1. SM: Preparation of Phenol from Salicylic Acid
2. Patent application US2488472; see also <a href="#parabenic">para-Hydroxybenzoic acid</a>

<h2><a id="salicylamide" href="#salicylamide"></a>Salicylamide</h2>

Salicylamide, the primary amide of salicylic acid, is commonly prepared by two chemical steps, the first being the carboxylic acid "activation" (for example, as the acyl chloride or methyl ester) and then the reaction with ammonia. However, a procedure for a direct amidation with urea exists.1 Salicylic acid is heated at 170-180 °C with urea in the presence of catalytic amounts of H3PO4 to give salicylamide.
1. Patent application DE869639.

<h1><a id="styrene" href="#styrene"></a>Styrene</h1>
<h2><a id="styreneoxide" href="#styreneoxide"></a>Styrene oxide</h2>
There are hundreeds of literature examples of styrene epoxidation in the literature, but few use easily accessible reagents. Of these, the epoxidation with Oxone, hydrogen peroxide with a catalyst, sodium percarbonate or perborate might be most suitable for an amateur.1 Another option is the epoxidation through the chlorohydrine (with hypochlorites or N-chloroimides). One of these methods is the epoxidation with trichloroisocyanuric acid in an aqueous acetone.2
1.
2. SM: Styrene oxide with TCCA

<h2><a id="styrenecloh" href="#styrenecloh"></a>Styrene chlorohydrin</h2>
Styrene chlorohydrin or 2-chloro-1-hydroxyethyl)benzene can easily be prepared by cochlorination of styrene with trichloroisocyanuric acid in aqueous acetone.1 The treatment of styrene chlorohydrine with bases gives styrene oxide.2 Its benzylic oxidation gives phenacyl chloride.3
1. Synthesis, 2003, 45-48. DOI: 10.1055/s-2003-36250
2. SM: Styrene oxide with TCCA
3.

<h1><a id="paracetamol" href="#paracetamol"></a>Paracetamol (p-hydroxyacetanilide)</h1>

Paracetamol or acetaminophen is a active pharmaceutical ingredient that is inexpensive and sold in large dosage forms (e.g., 0.5 g tablets, commonly with only very small amounts of binders and other excipients, if at all). Most excipients can be removed by dissolving tablets in acetone, filtering the insolubles and evaporating the filtrate.1 Crude paracetamol can be recrystallized from water or aqueous acetone to remove any water insoluble excipients and improve purity. Its main modes of reactivity are the reactions with electrophiles (it is nucleophilic at all aromatic positions as well as at O and N), it can readily be oxidized, and the reactions at the anilide carbonyl group (e.g., hydrolysis).
1. Paracetamol - a curriculum resource

<h2><a id="aminophenol" href="#aminophenol"></a>para-Aminophenol</h2>
Acidic hydrolysis of paracetamol can be used to prepare para-aminophenol.1
1.

<h2><a id="benzoquinone" href="#benzoquinone"></a>para-Benzoquinone</h2>
Oxidation of paracetamol under hydrolytic conditions gives para-benzoquinone.1 CAUTION: para-Benzoquinone is toxic, readily sublimates and tends to stain everything.
1.

<h2><a id="meoacetanilide" href="#meoacetanilide"></a>para-Methoxyacetanilide</h2>
Paracetamol can be easily O-methylated when deprotonated. The methylation is highly selective for the phenolic group. Methylation is achieved with several common methylating reagents, mainly dimethyl sulfate or methyl iodide.1 Nevertheless, methylations with trimethyl phosphate2 and methyl nitrate3 have also been described. The product can be hydrolysed to p-anisidine or used for several other derivatizations (N-alkylations, electrophilic aromatic substitutions, etc.)
1. SM: Paracetamol --> 2,5-dimethoxyallylbenzene
2. SM: Attempted Methylation of Paracetamol with TMP
3. SM: Methylation of phenols with Methyl Nitrate

<h2><a id="ohno2acetanilide" href="#ohno2acetanilide"></a>4-Hydroxy-2-nitroacetanilide</h2>
https://www.sciencemadness.org/whisper/viewthread.php?tid=97...


<h1><a id="tartaric" href="#tartaric"></a>Tartaric acid</h1>

<h2><a id="pyruvic" href="#pyruvic"></a>Pyruvic acid</h2>
When the tartaric acid (any stereoisomer) is heated in the presence of an acid catalyst, water eliminates to give the unstable 2-oxo-succinic acid which immediatelly decarboxylates under the reaction conditions. The formed pyruvic acid needs to be distilled as it forms to prevent its decomposition. Thus heating an intimate mixture of tartaric acid and potassium hydrogen sulfate at 210-220 °C is an effective method for the synthesis of pyruvic acid.1
1. Furniss, Hannaford, Smith, Tatchell: Vogel's Practical Organic Chemistry 5ed, 1989, pp 740.


<!-- bfesser_edit_tag -->[<a href="u2u.php?action=send&username=bfesser">bfesser</a>: tweaked <em>Org. Syn.</em> links]

[Edited on 3.11.13 by bfesser]



[Edited on 22/12/2013 by Nicodem]




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[*] posted on 30-10-2013 at 12:55


This is a lovely idea and excellent work, well done!



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[*] posted on 2-11-2013 at 16:37


I love the idea, one suggestion for organization: first should be chemicals that are available otc to everyone and then chems that can be made one step from that, then what can be made from that etc..

For example

Benzoic acid first chem otc
Benzamide one step from urea
Aniline from benzamide

I hope you understand because I dunno how to explain.
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[*] posted on 2-11-2013 at 18:14


Do you realize how complicated that would get? It's impractical.



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[*] posted on 3-11-2013 at 04:22


For some reason when I click on any of the orgsyn links they show up blank. But other than that this is an incredibly useful source.
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[*] posted on 3-11-2013 at 09:43


@Dariusrussell

It seems orgsyn.org have changed the way their site can be accessed. looks like you must first go thru' the warnings & disclaimer page before you are shown any preparations.

So first go to www.orgsyn.org

then click on "search text"
copy-paste "Diacetone alcohol" or any of the compound name who's preparation you are searching
Select "title" and then GO.

You will then be directed to warnings & disclaimers. Once you accept that then the prep is displayed.

gsd
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[*] posted on 3-11-2013 at 11:27


Yeah thats what I ended up doing. Just thought I'd let Nicodem know the links are sort-of broken.
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[*] posted on 3-11-2013 at 11:45


I edited the post and tweaked all the <em>Org. Syn.</em> links; they should all work fine now. I hope this helps. :)

<strong>Nicodem</strong>, I hope you don't mind that I edited your post&mdash;just say the word and I'll keep my hands off. I'd also like to volunteer my time and skills in coding. With my help, maybe you could be freed up to focus on the organization and collection of topics/links, and I can take care of keeping the code un-broken. I love tedious jobs.

Finally, I just want to say that I really like this project so far. I think I can safely speak for us all when I say that we appreciate everything you do. Maybe some day <em>elements</em> from my topical compendium could be integrated into your index&mdash;or even the compendium in its entirety.

[Edited on 3.11.13 by bfesser]




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[*] posted on 3-11-2013 at 11:51


Aah, so that's why I couldn't open them!
great idea Nicodem!




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[*] posted on 4-11-2013 at 08:58


Any non-moderator volunteers at all?

We need at least three volunteers, or else this will end up as just another dead end. Don't expect me to invest any work into this, except for compiling the text into a whole.

Quote: Originally posted by bfesser  
I edited the post and tweaked all the <em>Org. Syn.</em> links; they should all work fine now. I hope this helps. :)

Thanks, but the references are not formated yet, so you pretty much overworked it. The URL addresses will have to be incorporated to the references anyway.
Quote:
<strong>Nicodem</strong>, I hope you don't mind that I edited your post&mdash;just say the word and I'll keep my hands off. I'd also like to volunteer my time and skills in coding. With my help, maybe you could be freed up to focus on the organization and collection of topics/links, and I can take care of keeping the code un-broken. I love tedious jobs.

I'm more than happy to leave all the compiling and editing work to you. There is only this slight problem, that without any volunteer there will be nothing to edit at all.
Quote: Originally posted by Random  
I love the idea, one suggestion for organization: first should be chemicals that are available otc to everyone and then chems that can be made one step from that, then what can be made from that etc..

For example

Benzoic acid first chem otc
Benzamide one step from urea
Aniline from benzamide

I hope you understand because I dunno how to explain.

There are several reasons on why I think your suggestion is unreasonable. Here are a few:
- It would take at least 10 times more work and there is currently no will even for the proposed amount of work;
- Anyone who is interested in doing a multi-step synthesis is more than likely competent enough to do his own literature work and has no need of such an index;
- Any additional step requires additional reagents, which is in conflict to the core idea of the index of readily accessible experiments (OTC substrate with common lab. reagents);
- You suggest others to do many times more work, but don't volunteer to participate (bad taste).




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[*] posted on 5-11-2013 at 07:24


Quote:
Anyone who is interested in doing a multi-step synthesis is more than likely competent enough to do his own literature work and has no need of such an index

That is why I do not understand your idea.
Such an index would be (maybe) useful if created ~10 years ago.

Quote:
In order to promote organic synthesis on the forum, I thought to create a sticky thread with an index of suggestions for synthesis practice for those interested.

Promote, but to whom ?
To users attempting to "extract any chemicals from household things" or "make meth from dog's shit" or "extract methanol from gasoline" etc. ? No
To users "interested" or "advanced" ? See the first quotation.

Besides, there is very important "OTC substrate with common lab. reagents". Are TMSCl,PhNHNH2,Et3N,MeCN,NaCN,Ac2O,AlCl3... readily available ? For the most users - they are not.

For a longer time, SM promotes only vacuity, idle posts about nothing. Examples from this topic only :

"This is a lovely idea
I love the idea ... I hope you understand because I dunno how to explain.
Do you realize how complicated that would get? It's impractical.
For some reason when I click on any of the orgsyn links they show up blank
I hope you don't mind that I edited your post
Aah, so that's why I couldn't open them!great idea"
.....








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[*] posted on 5-11-2013 at 09:16


<strong>kmno4</strong>, if you don't have any constructive criticism, don't post. If you believe that "SM promotes only vacuity, idle posts about nothing," then you're more than welcome to leave. Don't waste our time with your negativity and hypocrisy (your post is as vacuous or more so than any other in this topic).

tl;dr: Contribute something positive or shut the fuck up.




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[*] posted on 5-11-2013 at 11:42


Quote: Originally posted by kmno4  
That is why I do not understand your idea.
Such an index would be (maybe) useful if created ~10 years ago.

Yes, it is true that today, unlike 10 years ago, one can access almost any scientific literature (assuming no inhibition toward breaking the copyright law). In my days I had to go physically to the library and spend hours with the Chemical Abstracts to find any references. Now they are just a few clicks away. Perhaps for this reason, it is difficult for the new generations to appreciate the work invested into finding the right articles. The more accessible science becomes, the more the potentially interested members become lazy and unable to do any literature work by themselves.
The premise of this index is that among these lazy members there are a few who would actually do some work if stimulated and steered in the right direction. Hence the idea of promoting experimental work by listing experimental proposals and making synthesis references more accessible. Perhaps it is naive, and the (lack of) any proper response to this thread apparently confirms this is so, but in my naivety I found it worth trying.
Quote:
Besides, there is very important "OTC substrate with common lab. reagents". Are TMSCl,PhNHNH2,Et3N,MeCN,NaCN,Ac2O,AlCl3... readily available ? For the most users - they are not.

In my amateur times I had access to a variety of commercial reagents, solvents and other compounds, gathered from all around (of the ones you list I had PhNHNH2, Et3N, MeCN, Ac2O, but for example, for a long time I could not get any AlCl3). These sources complemented with the so called OTC sources were enough to do all kind of preparative experiments in organic synthesis. From your posted experiments, I can see you have the same mix of sources. Why do you think it is any different with others?
Quote:
For a longer time, SM promotes only vacuity, idle posts about nothing. Examples from this topic only :

You are wrong. The moderators do not promote such things. We fight against it. perhaps not as aggressively as you would like, but we do.

So are you joining as a volunteer, or not?
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[*] posted on 5-11-2013 at 12:47


I think that the idea behind the thread is interesting to some
people. For me personally, I tend to work in the reverse
direction. If there is something that I would like to synthesize,
then I am motivated to go find out what is needed to be able to
do it. If I want to make 4(5)-methylimidazole, then I go
looking for formaldehyde, ammonia, and then I raid several
sugar packets out of the kitchen. I don't approach it from the
perspective of, "I wonder what I can make with this sugar
packet...", although I think some people are motivated that way.

The point is that I hope you don't take the apparent lack of
response in a discouraging way. If this thread is sticky'd
somewhere, I will probably add some links of my own to it.
But it will probably be few posts, over a long period of time.
I'm more motivated to post links to things that I have actually
done, instead of posting links to other people's stuff. That is
just where my interests are.
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[*] posted on 5-11-2013 at 13:19


Alright so oxidation of xylene yields phthalic acid isomers. Phthalic acid could be isolated because it readily forms anhydride which sublimates. Unlike other two IIRC.

Citrazinic acid can be made from citric and urea. But we haven't researched the whole procedure completely, as far as I know I attempted this many times and failed to isolate the product. I'll give it a go one more time since I have more solvents now.

[Edited on 5-11-2013 by Random]
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[*] posted on 5-11-2013 at 17:43


Quote: Originally posted by Nicodem  
The premise of this index is that among these lazy members there are a few who would actually do some work if stimulated and steered in the right direction. Hence the idea of promoting experimental work by listing experimental proposals and making synthesis references more accessible.
For "lazy", you could also read "overwhelmed". With a field so large, there's a certain minimum competence needed to know even how to start. It's very easy to start looking up something and immediate hit the incomprehensible. What would help, I would think, is to treat such an index in the same manner as an annotated bibliography, with a bit of commentary about why a synthesis is interesting or where it fits in the larger picture.
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[*] posted on 14-11-2013 at 06:42


A thought that came to my mind now when I read Nicodem's post again is how little we appreciate the effort some members do to help us. Including Nicodem who I remember that he explained very extensively when I asked something, back in 2010 while I was inexperienced newcomer.

Even if we had a few arguments I could say only positive things today and I support the idea.
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[*] posted on 22-11-2013 at 19:34


I've done a number of quick funsy organic reactions. If I get enough time to transfer any here I will, other-wise it will have to wait until winter break unfortunately.



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[*] posted on 23-11-2013 at 01:29


Thank you for offering help.

For the beginning it would be of great help, if the authors of the SM reports would write the pertaining mini-reviews themselves (at least those members that are still active).

Also, even those members who are too "overwhelmed" to do any literature work, could at least write down the starting materials (OTC compounds) introductions, things like where can they be commonly obtained, how to purify them, what's their properties and typical chemistry, etc.
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[*] posted on 30-11-2013 at 04:16


I've got something big in the pipeline. But its taking time to piece it all together. Hopefully it will be useful.
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[*] posted on 30-11-2013 at 16:46


Nicodem, what do you mean by mini reviews?

Here also seems to be the best place to ask this: Should I write up articles in prepub on the preparation of compounds of which the syntheses and guides are found on the web, but no such thing exists in prepub?
I have been systematically going through vogel's textbook doing syntheses, but have never really bothered to do an article on them as others can be found elsewhere (e.g. nitrobenzene, bromobenzene, toluenesulfonic acid,...) should I write an article with pictures nonetheless so that SM has one too?





all above information is intellectual property of Pyro. :D
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[*] posted on 8-12-2013 at 08:12


Quote: Originally posted by Pyro  
Nicodem, what do you mean by mini reviews?

See the first post of this topic. This is the topic of this topic, you know?
Quote:
Here also seems to be the best place to ask this: Should I write up articles in prepub on the preparation of compounds of which the syntheses and guides are found on the web, but no such thing exists in prepub?

Anything that is any kind of a contribution (either to the techniques, methodology, knowledge or science) is welcome in the Prepublication section. Just an account of how you repeated some reputable prior art is pretty much worthless. It needs some sort of a contribution in the form of new conclusions or cautions based on the observations, analyses, measurements, unexpected occurrences, failure modes, critical parameters, runaway conditions, mishaps, improvements, and other issues not yet described in the prior art.
I guess we should have a sticky thread with some sort of disclaimer in the Prepublication section, but I never thought that anybody would actually need it. After all, the section subtitle says: "A gathering place for topics intended to join our collection of articles." So it appears obvious that the topics are a sort of articles put forward for peer review.
Quote:
I have been systematically going through vogel's textbook doing syntheses, but have never really bothered to do an article on them as others can be found elsewhere

Like I said, if you come to any new conclusions, you obviously have something new to contribute. In such case, you should write an article for the Prepublication section. We have very few, if any, scientific contributions in that section, but we have some very valuable contributions from the field of methodology, cautions, and some technique improvements. Obviously, you are not expected to have a scientific contribution, when all you do is repeating published procedures without any development or research, but it is still very likely that you encounter other valuable information to share.




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