Author Topic: P2P - new idea.  (Read 3577 times)

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fallen_Angel

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P2P - new idea.
« on: November 13, 2002, 09:37:00 AM »
P2P - new idea.

See it in Russian:

Post 378325 (missing)

(fallen_Angel: "P2P - íîâàÿ èäåÿ.", Russian HyperLab)

Recently I have invented brand new a path of synthesis P2P

Response:

1. 2Na + 2NH3 - > 2NaNH2 + H2
2. NaNH2 + HCCH - > HCCNa + NH3
3. C6H5CH2Cl + HCCNa - > C6H5CH2CCH + NaCl

4.                       HgSO4
  C6H5CH2CCH + H2O - > C6H5CH2COCH3

Or
4 (a). C6H5CH2CCH + HBr - > C6H5CH2CBr2CH3
5 (b). C6H5CH2CBr2CH3 + NaOH - > C6H5CH2COCH3 + 2NaBr

The first 3 stages - response in one vial.
4 stages - good known response Kutcherov
4 (a), 5 (b) - optional versions.

In 3 and 4 stages are guessed high (not less than 80 %) yields. This method very simple, all reagents - benzyl chloride, ammonia and calcium carbide (acetylene) OTC, about sodium - whom as, sulphate of quicksilver made be easeli. Quicksilver you are purchase radioshops, where there is a lot of cheap quicksilver.

For deriving sodium amide it is not necessary to take fluid(liquid) ammonia, though all you need is a dry ice and artful cooler - tube a dia of centimeter 3-4 and lengthy 40-50 cms, second soldered from one endb a dia 2-3 cms, is interposed in first. In interior the dry ice is filled in and a little acetone is flooded. In the device the gaseous ammonia is passed, he condences and flows down in a flask.
Though probably it is easier sodium amide to receive, passing ammonia above heated sodium.

Response 3-phenil-1-propyne with water - we add the catalytic agent and is boiled with a reflux condenser, and then distillate phenilaceton with steam.

And more:
We to pulp carbide in a dust, we add benzyl chloride (or its solution?):
CaC2 + C6H5CH2Cl - > C6H5CH2C2CaCl
Then we add water, we receive 3-phenil-1-propyne..
Interesting idea, and sodium is not necessary, and generally ÎÒÑ  :)  

Problems:
1. At deriving 3-phenil-1-propyne generally, there is a migration of acetylene bond or formation of cyclic yields?
2. In case of migration of bond
C6H5CH2CCH - > C6H5CCCH3
The response Kutcherov with formation P2P  or propiophenone will work? It is very important for knowing for further operation. On atom of carbon, adjacent with a benzene ring some negative charge will be , that allows to go with formation P2P, but practically I do not know.
3. There will be a response of benzyl chloride immediately with carbide? What solvents it is better to use?
4. Is it  possible to use instead of fluid ammonia diethyl amine, or other amine? It would simplify a method.


Fallen_Angel


Rhodium

  • Guest
Alternative Grignard route
« Reply #1 on: November 13, 2002, 10:25:00 AM »
An idea to eliminate the liquid ammonia and sodium needed in the first step, you can bubble acetylene gas (from calcium carbide/water) through a solution of ethylmagnesiumbromide in ether (grignard from ethyl bromide and magnesium) to form ethynylmagnesiumbromide. This reagent is then used to alkylate benzyl tosylate (para-toluensulfonate ester of benzyl alcohol) to give 3-phenyl-1-propyne.

hermanroempp

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Synthesis of Ethinylmagnesium bromide
« Reply #2 on: November 14, 2002, 06:35:00 PM »
Ethinylmagnesium bromide:

a) Ethylmagnesium bromide reagent in 140 ml of dry THF is prepared under nitrogen from 4.8 g (0.2 mol) magnesium turnings (and the corresponding amount of ethyl bromide, 0.2 mol = 21.99g. Grignard reagent is prepared in the usual manner).
b) In a (roundbottom) flask, equipped with stirrer, dropping funnel and gas inlet tube 80 ml of THF are saturated with dry acetylene gas. During saturation, the still warm Grignard solution prepared in (a) is added via the dropping funnel in 3-5 ml portions. Below 20°C ethylmagnesium bromide crystallizes from the Grignard solution, but the resulting suspension can be added without problems (this is not always true, the suspension can clog your dropping funnel, so the solution should be added while it is really warm). After the addition of the Grignard reagent has ended, at 25°C a solution of ethinylmagnesium bromide results. On cooling it yields an easy to handle (see my previous remarks) suspension.

Notes:
- a local excess of acetylene must always be present or the thick, oily ethinyl-bis(magnesiumbromide) will be be the main product
- temperature on addition of the Grignard reagent must be kept at 30-35°C for best yields, above 40°C the bis-product will result in exothermic reaction.
- yield of the ethinylmagnesium bromide is 90-95 %, which must be considered in further reactions


[Translated from "Houben-Weyl: Methoden der organischen Chemie"; Vol. unknown, 1954, Thieme Verlag, Stuttgart]
Italics mine

Other references:
- E.R.H. Jones, L.Skattebol and M.C. Whiting, Journal of the Chemical Society, London, p. 4765 (1956)
- R. Werner, Chemische Berichte 91, 168 (1958)

I've prepared ethinylmagnesium bromide myself this way (intermediate for the synthesis of substituted furans) and it worked really good, no problems.

Quidquid agis, prudenter agas et respice finem!

Disciple

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Awesome!!
« Reply #3 on: November 20, 2002, 01:30:00 AM »
We to pulp carbide in a dust, we add benzyl chloride (or its solution?):
CaC2 + C6H5CH2Cl - > C6H5CH2C2CaCl
Then we add water, we receive 3-phenil-1-propyne..

So is He saying this is maybe a 4 step synth starting from toluene and Ca HypoChlorite and Calcium carbide and whatever catalyst for the final conversion to phenylacetone. If so Awesome.
Can anyone tell me if Calcium Carbide is still readily available where you are. Used to be sold for use in miners lamps, to produce acetylene. Is it hard to Synth.

MMM

  • Guest
Carbide can be made in a furnace at about 1200C ...
« Reply #4 on: November 21, 2002, 05:07:00 AM »
Carbide can be made in a furnace at about 1200C from memory. You use the same furnace to make CaO from limestone, then mix it with ground charcoal and put it back in the furnace.

Only if you need CaC2 tho, in Russia they dont have Acetylene bottles.  They use portable gas generator and a bottle of O2 for their Oxy-Acetylene equipment. I think I have even seen small plumbers kits with disposable bottles.

MMM

Point of interest, Oxy-Acetylene equipment was invented by an unknown person who left the gear behind after using it to cut open a safe in France. :D

When the day is bad,and life's a curse
CHEER UP!!! Tomorrow may be Worse!!
('HAGAR' Comic)

fallen_Angel

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carbide
« Reply #5 on: November 21, 2002, 07:23:00 AM »
I life in Russia, here carbide as muds.

It is use for deriving acetylene, level with acetylene gas from a balloon.

Polverone

  • Guest
CaC2
« Reply #6 on: November 21, 2002, 07:40:00 AM »
I hate to contribute in such a minor fashion to such an illustrious thread, but let it be known:

calcium carbide is still readily available in the US. I assumed it had gone the way of the dinosaur, just like nitric acid at the druggist's, until I saw it at a local hardware store that is part of a national chain. Some people still prefer carbide lamps for illumination, and a few minutes spent with a search engine will reveal a number of retailers supplying the material. It is "hazardous when wet," obviously, so expect to pay for truck freight if you can't find it locally. It may be time to add "caving" to your list of imaginary hobbies (joining photography, high performance car racing, and animal husbandry).

19th century digital boy

pHarmacist

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why?
« Reply #7 on: November 21, 2002, 11:35:00 AM »
You guys often say, 'see it in russian'... Why should we do that? We don't speak russian....

"Turn on, Tune in and Drop Out"

Antoncho

  • Guest
That's nothing, really.
« Reply #8 on: November 21, 2002, 05:17:00 PM »
In most cases (like this one) this phrase is used merely for providing the reference to the original text - just in case someone happens to speak Russian or decides to use some translator program.

There was only one case of these words said 'seriously', and that was beecause the person who said that seriously lacked common sence :)  :-[


So take it easy i pray you ;D


Antoncho

pHarmacist

  • Guest
Ok.. tnx for clarifying that
« Reply #9 on: November 21, 2002, 05:28:00 PM »
By the way, I appreciate you translating Zealot's work...

"Turn on, Tune in and Drop Out"

hermanroempp

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Wrong intermediate
« Reply #10 on: November 21, 2002, 06:32:00 PM »
Disciple:
Sorry to rain on your parade,but...you will most likely end up with (Ph-CH2-C2)2Ca (dibasic salt)because Ca is more basic than Mg...this compound won't behave like the monobasic salt...so...the way to go employs the Grignard compound of acetylene (ethinylmagnesium bromide), which is reacted with benzylbromide (for best yield) to get your 3-phenyl-1-propyne in 70 % yield, according to "H. Wieland, H. Kloss, Liebigs Annalen der Chemie 470, 201 (1928)".
Another way to 3-phenyl-1-propyne is bromination of allylbenzene to yield 1,2-dibromo-3-phenyl-propane, elimination of the bromine by distillation of 1,2-dibromo-3-phenyl-propane from a solution of KOH in triethyleneglycol and isomerisation with NaH (or better NaNH2) in toluene to yield the sodium salt of 3-phenyl-propyne, which is decomposed with diluted HCl or better with glacial acetic acid to finally yield your 3-phenyl-propyne.

Quidquid agis, prudenter agas et respice finem!

Nitroxamide

  • Guest
another variation
« Reply #11 on: October 24, 2003, 10:05:00 PM »
The general idea being discussed here actually just crossed my mind a few days ago - glad to find some info on it!


We to pulp carbide in a dust, we add benzyl chloride (or its solution?):
CaC2 + C6H5CH2Cl - > C6H5CH2C2CaCl
Then we add water, we receive 3-phenil-1-propyne..




Wouldn't the following side reaction be crippling to yields?

BzC2CaCl + BzCl ----> BzC2Bz + CaCl2

My idea was this: prepare a C2H- Ca salt via reaction of CaC2 with a dry liquid amine (such as diisopropylamine, which is easily prepared from ammonia, acetone, and Al/Hg amalgam).

As in:

CaC2 + R2NH ----> Ca(C2H)(R2N)

Amines are less acidic than the first hydrogen in acetylene, but (if I remember correctly) more acidic than the second.

And there we have it - our reagent for the nucleophilic substitution:

3BzCl + Ca(C2H)(R2N) ----> BzC2H + Bz2NR2Cl + CaCl2




neo

  • Guest
this method needs ..
« Reply #12 on: November 23, 2003, 04:37:00 AM »
to get the p2p...wouldn't it be great to have a chamber..with pyrolysis..5000 psi and heat...with acetone, and ammonia...to make the 1-phenyl-2aminopropane??

but one uses 1-phenylethanol+nh3 ==>(heat+5000 psi) to make the methylphenethylamine..

and...
benzaldehyde (almonds)+ch3mgbr(methylmagnesium bromide) to the enol intermittent of c6ch3chomgbr ==>h+cl- gives you 1-phenyl-1-ethanol.

Nicodem

  • Guest
What about copper?
« Reply #13 on: November 23, 2003, 09:34:00 PM »
Unfortunately the alkylation of CaC2 would produce only the dialkylated compound since CaC2 is not soluble in aprotic solvents and therefore any molecule of CaC2 reacting with BnCl would get in to the solution and be further alkylated.

There is a more simple way to make alkylacetilenes like benzylacetylene. You can use copper acetylides, which are really easy to prepare (and stable in protic solvents, even water). Therefore I propose this idea:

Ar-CH2-Cl + Cu2C2 ---> Ar-CH2-C2-Cu  + Ar-CH2-C2-CH2-Ar  + CuCl

Ar-CH2-C2-Cu should be transformed in Ar-CH2-C2-H with some diluted acid like HCl and you would end up with a reusable amount of CuCl. Air must be avoided since Cu-C2-R type of compounds couple in to R-C2-C2-R when in solution (this is used as a reaction called the Glaser coupling). Again, the problem is the concurrent reaction of dialkylation.
Since the CuC2H probably does not exist, I see no other solution than to use a large excess of Cu2C2.
These kind of reactions are usually done in pyridine or DMF, but I think any solvent where Cu2C2 is at least slightly soluble would do the trick or you cold use the minimal amount of pyridine or some other amine in ether, THF or maybe even protic solvents like IPA. Actually cuprous acetylides can by formed in situ in the presence of some amine (usually EtNH2) and CuCl as catalyst.

I don’t have any references at hands but this info is taken form Guidebook to Organic Synthesis (third eddition); Mackie, R.K.; Smith, D.M., Aitken, R.A.(Pearsn Education Limited 1999).
I’m sure there is some good review article somewhere out there. Maybe someone could find it? There are some refs concerning organo-cuprous reactions at the end of the book but I haven’t checked them yet:
G.H. Posner, An introduction to Synthesis using Organocopper Reagents. Wiley, 1980; Krieger, 1988.
J.F. Normant, Synthesis, 1972, 63.
G.H. Posner, Org. Reactions, 19, 1 (1972); 22, 253 (1975).

I used to make Cu2C2 by bubbling acetylene (from CaC2) into a solution of cuprous (I) chloride (CuCl, not CuCl2!) in aqueous ammonia. Cu2C2 precipitates as a brown to dark red stuff that is highly explosive if dried and ignited (that’s the reason why I was making it when still young and inexperienced - by the way, Ag2C2 is even more dangerous). The only problem is that you have to avoid oxygen since it oxidizes the Cu1+ to Cu2+ and this one makes carbon out of acetylene (by the coupling reaction). Oxidation was avoided by adding some Na2S2O3 which keeps the copper in its +1 state.

It is also mentioned that the monoalkylations of acetylene proceed with good yields with monosodium acetylide (NaC2H) made with sodium amide in liquid NH3 from acetylene (not easy enogh for me). I was thinking if NaOH and grinded CaC2 would react in THF giving a solution of NaC2H and a precipitate of CaO? Or maybe using a salt more soluble in THF, like sodium benzoate and benzoic acid, each 1/2 molar equivalent of CaC2. Wouldn’t that make calcium benzoate(s) and NaC2H in THF? Adding BnCl would make a Bn-C2H and NaCl.

Just as an stimulation to broaden this thread to more than just the ordinary P2P:
Many of the most interesting benzyl chlorides can be easily made with paraformaldehide and conc. HCl in acetic acid solution from methoxybenzenes. My yield of 4-bromo-2,5-dimethoxy-benzylchloride was 53% from 1,4-dimethoxy-benzene in two stages:

1,4-dimethoxybenzene + KBr + KBrO3 / HCl(aq), CH2Cl2 (two phases) ---> 2-bromo-1,4-dimethoxybenzene

2-bromo-1,4-dimethoxybenzene + (HCHO)n + HCl(aq) / AcOH ---> 4-bromo-2,5-dimethoxy-benzylchloride

Rhodium

  • Guest
interesting, interesting
« Reply #14 on: November 23, 2003, 11:40:00 PM »
Nicodem: I'm really interested in reading a detailed procedural description of the 2,5-Dimethoxybromobenzene -> 2,5-Dimethoxy-4-Bromo-Benzyl Chloride chloromethylation reaction.

Nicodem

  • Guest
2,5-Dimethoxybromobenzene Chloromethylation
« Reply #15 on: November 24, 2003, 09:39:00 AM »
OK, here are the details. Chloromethylation is quite easy if you guess how activated the aromatic ring is. Yields are usualy in the range of 60 to 90% when using acetic acid as a solvent. When using a two phase system and alkylbenzenes (toluene, xylene, 1,2,4.trimethylbenzene...) the yield are 40-60%. PTC catalysts are reported to give excelent yields in such a case.

Preparation of 2-bromo-1,4-dimethoxybenzene:
In a 150ml flask there was added 3g of 1,4-dimethoxybenzene in 25ml DCM, 2g potassium bromide in 20ml 12% aqueous HCl. The resulting two phases were being stirred while an solution of 1.23g of KBrO3 in 18ml of water is being added as slowly enough so that solution prevented of becoming to much dark red (to allow the Br2 some time to react and discolor) and the temperature was not allowed to get over 25°C. This took about one hour and the reaction mixture was left standing for one hour more. The organic phase was separated and the aqueous was extracted DCM. The combined organic phases were washed with 15ml water containing a pinch of ascorbic acid (to destroy the some excess Br2), then with 15ml water only, dried with Na2SO4. The DCM was evaporated leaving 3.9g of light brown oil, presumably 2-bromo-1,4-dimethoxybenzene (83%). Freezing the oil and then letting it melt on ambient temperature produced some cloudiness presumably from some unreacted 1,4-dimethoxybenzene. It was estimated this is probably les than 3% and the oil was used for the chloromethylation without being filtered.
Note: Instead of KBrO3 you can use KMnO4, Na2Cr2O7, NaOCl of some other suitable oxidant and recalculating the amounts needed.

Preparation of 4-bromo-2,5-dimethoxy-benzylchloride:
In a 50ml flask there was added 290mg of paraformaldehide, 8ml of glacial acetic acid, 5ml 31% HCl(aq) an 2g of 2-bromo-1,4-dimethoxybenzene. While stirring there was bubbled some HCl gas from tube connected with a flask containing NaCl reacting with conc. sulphuric acid (not much is needed, 5 to 10ml will do). After 6h of stirring at ambient temperature there was added 30ml of cold water and the solids filtered of, washed with a lot of water and then with 3ml of cold ethanol. The white to slightly pinky solid was left drying over CaCl2. This left 1.52g of the product, presumably 4-bromo-2,5-dimethoxy-benzylchloride (63%).
Note: The halogens deactivate the benzene ring toward the electrophiles. The yield for a similar synthesis of 2,5-dimethoxy-benzylchloride was better (79%). Instead of parafomaldehide, trioxane can be used, which is esentialy the same but can be bought in some hobby shops as fuel tablets for the stem locomotive models or something like that or as fuel tablets for camping.

This product was used for the sintesis of the benzylpiperazine derivative and of 4-(4-bromo-2,5-dimethoxyfenil)-butan-2-one. But one can also imagine a Sommelet reaction to produce the 4-bromo-2,5-dimethoxybenzaldehide (never tried though).

Rhodium

  • Guest
Dimethoxybromobenzene chloromethylation
« Reply #16 on: December 20, 2003, 11:24:00 PM »
Application de la Chlorométhylation a la Synthèse D'Acides Polyalcoxy-Phénylacéticques
Raymond Quelet

Bull. Soc. Chim. France [5] 20, C46-C48 (1953)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/quelet.chloromethylation.pdf)

This french article is supposed to discuss the chloromethylation of dimethoxybenzene and dimethoxybromobenzenes, but I cannot make out any useful info from it as I cannot français déchiffrage. Could anyone fluent in the language look over the document and see if you find any useful information in it?


hypo

  • Guest
very short summary...
« Reply #17 on: December 21, 2003, 09:37:00 PM »
they want to go to the phenylacetic acid by the following reaction sequence:

dimethoxybenzene --(chloromethylation)--> veratryl chloride --(NaCN)--> nitrile --(hydrolysis)--> acid

but: veratryl chloride is too reactive and "condenses with itself". this
is especially bad for industrial synthesis. so they brominate the dimethoxy
benzene, do the above reaction sequence (the chloride is much more stable now)
and yank off the bromine with Zn.

the same for other dimethoxy benzenes.

shall i translate the experimental?


karel

  • Guest
Hello Nicodem! I am curious if you also ...
« Reply #18 on: June 22, 2004, 08:56:00 PM »
Hello Nicodem!
I am curious if you also observed formation of 6-bromo isomer during chloromethylation reaction as I was

Post 299551

(karel: "Chloromethylation", Chemistry Discourse)
Or your chloromethylation at room temperature gave only desired 4-bromo compound?
Regards

Karel

Nicodem

  • Guest
The 6-bromo isomer issue
« Reply #19 on: June 22, 2004, 10:12:00 PM »
Hi Karel
I have no idea as I currently don't have access to any analytical tool whatsoever. I can’t do even a simple TLC. As soon as I will be able (in the next two months hopefully) I will also give more detailed information. This is an issue that I’m also very interested in since I found your old post. However I think about 15% of the product is actually a dimer (judging from the remaining inert component in certain reactions I used the product for). So a recrystallization step should bee added to the procedure above.