Hive Methods Discourse

	Main Index Search Register Login Who's Online FAQ Links
	Main Index Search Register Login Who's Online FAQ Links

	1 Online, 0 Active		You are not logged in

This is a historical archiveThe forum is read-only. Private information has been removed. It is not possible to login.

	Methods Discourse

All 18 posts Subject: Acetamide Please login to post Down

ADDkid
(Hive Bee)
12-26-03 21:16
No 479166
User Picture       Acetamide

Swig had some urea, and some concentrated Acetic acid, although not G.A., He then setup a clasien adapter followed by a condenser without water, Heated in reflux. He notice that ammonia smell was present very strongly (made whole room smell like urine) towards the end of the reaction. Small presence of the carbon Nitrogen salt formed inside the condenser at the very end of the rxn. Swig has read that the amide can be distilled at pure form at around 200C and most coming over at 214-216c. Swig notice that the product became very dry, and never could reach those high temp with the soild. It look like it was starting to burn or become unstabe. I failed to mention that the initial color of the urea and acetic acid was almost colorless. As the reaction proceeded, the color turn into a dark yellow. Also when trying to distill the amide, swig's "air" condenser and receiving flask filled with white crystals, which he belives is the ammonium salt, started a little above 100c.
After trying to clean, Swig was left with a very soft yellow powder, which had no smell, compared to the weirld smell (almost like cookies with a ammoniua smell. Can somebody help me in trying to figure out why it is yellow. Also it is not very souble in water, with acetamide is soluble at 20c 22000g/l.

P.S. I was going to try to just extract with toluene and water, since amide are neutral, it should go in the toluene layer, right. Addkid

El_Zorro
(Hive Addict)
12-26-03 22:08
No 479168
      Read Eleusis's synth of acetamide.

Read Eleusis's synth of acetamide. If remember correctly, Acetamide melts at 80C, so you just have to use a water condensor with the "cooling" water heated to 80C to keep the acetamide a liquid. Those crystals you were getting in your condesor and recieving flask were probably acetamide.

It is seductive, way too seductive.    -Eleusis

Rhodium
(Chief Bee)
12-27-03 21:05
No 479358
User Picture       correction

The aqueous solubility of acetamide is 200g/100mL water.

^{The Hive - Clandestine Chemists Without Borders}

java
(Hive Bee)
01-11-04 22:34
No 481890
      Re: Acetamide

While on the topic of Acetamide,

"In general terms of synthesis of amides,such that they are compounds in which the -OH of the carboxylic acid has been replaced be -NH2.
These are prepared by heating the ammonium salts of carboxylic acids, water driven off by destillation.

RCOOH + NH3-->RCOO-NH4+-------heat---->RCONH2 + H2O

In the laboratory amides are more likely to be prepared by reaction of ammonia wih acid chlorides,

RCOOH----->RCOCl-----NH2---->RCONH2..." ( Ref. Organic Chemistry, Morrison & Boyd )

I noticed the reaction of Acetamide with OBr- to produce RNH2, the Hofmann Degradation (rearrangement) of amides. I noticed the source of hypobromite, and amide relatively cheap. Is there any bee with any experience making methyl amine through this procedure and assume correctly that NaOH and Br2, will work as my source of hypobromite......java

Note : Edited by Java 1-12-04

We're all in this world together,
http://www.aztlan.net

Nicodem
(Hive Bee)
01-12-04 09:43
No 481983
      Is there any reason common bleach (NaOCl)...

Is there any reason common bleach (NaOCl) isn't good for the Hofmann rearrangement?
I always thought Br2/NaOH is used in the lab only because it is easier to dettermine the amount of Br2 than the concentration of NaOCl. Anyone knows if there are other reasons, like lower yields or else?
It would sure by nice to just distill off MeNH2 from acetamide/NaOH/NaOH. Probably much better than the reduction of MeNO2.

“The real drug-problem is that we need more and better drugs.” – J. Ott

java
(Hive Bee)
01-12-04 16:27
No 482029
      RE: Hofmann rearrangement

Is there any reason common bleach (NaOCl) isn't good for the Hofmann rearrangement?

Nicodem ...In the lit only the -OBr will work, there's also a reaction that converts primary amines into N-halo or N,N-dihaloamines in which either the -OCl or -OBr will work here*. " In the Hofmann rearrangement , an unsubstituded amide is treated with sodium hypobromite( or sodium hydroxide and bromine, which is essentially the same thing) to give a primary amine that has one carbon fewer than the starting amide,( Ref. March's 5th edition pg.1411)

RCONH2 + NaOBr------>R-N=C=O------Hydrolysis---->RNH2

* March's 5th edition page 819

Ref. for review, see Wallis,E.S.; Lane,J.F. Org. React. 3,267, 1946

We're all in this world together,
http://www.aztlan.net

stratosphere
(Hive Bee)
01-12-04 18:54
No 482051
      at a theoretical level i don't see why ...

at a theoretical level i don't see why acetamide + hoffman wouldn't yield methylamine.

another reaction you might look into is 2CH2O + NH4Cl --heat--> CH3NH2(HCl) + CH00H
i can get you a reference for that rxn if you want it.

java
(Hive Bee)
01-13-04 17:06
No 482198
      Re: methylamine alternative synthesis

stratosphere,

Yes , why don't you post them for the benefit of the bee's reading the forum , and please comment on your experienced with the method , if it applies ......java

We're all in this world together,
http://www.aztlan.net

stratosphere
(Hive Bee)
01-13-04 17:25
No 482201
      i have no experience with the ...

i have no experience with the formaldehyde+ammonium chloride method, just saw it briefly referenced in one of my organic books and thought it sounded useful, heres the ref. it gave:

Gilman's Organic Synthesis I, pg. 347

yeild reported at 50%, not sure what thats relative to (perhaps theoretical yield), but with inputs that cheap it doesn't matter.
im also not sure of any of the details of the reaction conditions, would be interested to see it, if someone can dig it up.

Rhodium
(Chief Bee)
01-13-04 18:51
No 482217
User Picture       that synth is almost painfully well-known

https://www.rhodium.ws/chemistry/methylamine.html

^{The Hive - Clandestine Chemists Without Borders}

lugh
(Moderator)
01-13-04 21:09
No 482237
      Bee's Favorite Routes to Methylamine
(Rated as: good read)

The hypohalite route to methylamine is very well known to the bees as well, see:

https://www.rhodium.ws/chemistry/eleusis/methylamine27.html

and spiceboy's helpful comments in

Post 108635 (dormouse: "Methylamine via hoffman -Molly Heart", Novel Discourse)

and the article by Hauser et al from JCE 14 542-4 (1937)

smile

Chemistry is our Covalent Bond

Rhodium
(Chief Bee)
01-13-04 22:38
No 482241
User Picture       Methylamine HCl from Acetamide
(Rated as: excellent)

An Elementary Laboratory Experiment Involving the Hofmann Rearrangement:
The Preparation of Methylamine Hydrochloride from Acetamide by Means of Calcium Hypochlorite
C. R. Hauser and W. B. Renfrow, Jr.
Journal of Chemical Education 12, 542-544 (1937) (https://www.rhodium.ws/chemistry/methylamine.acetamide.html)

The well-known Hofmann reaction by which, an amide, in the presence of chlorine or bromine and an alkali, is converted into a primary amine with one less carbon atom, is of considerable interest in organic chemistry. The reaction may be used in going "down series," and it serves as a laboratory method for the preparation of a primary aliphatic amine. The reaction is of interest also because it involves a molecular rearrangement.

The Hofmann reaction is often illustrated in the laboratory by the preparation of methylamine hydrochloride from acetamide. It has been our experience,however, that when this experiment is carried out with bromine and alkali according to the directions given in many laboratory manuals, a considerable portion of the product consists of ammonium chloride.

In this paper directions are given for the preparation of methylamine hydrochloride from acetamide using commercial calcium hypochlorite and sodium hydroxide. The product obtained with these reagents is contaminated with only a small amount of ammonium chloride, and this can be removed by treatment with aqueous alkali as described below.

In this experiment, acetamide is first converted into N-chloroacetamide, which, in the presence of alkali, eliminates hydrogen chloride and undergoes rearrangement to form methylisocyanate. Hydrolysis of the latter gives methylamine which is isolated as the hydrochloride. It should be pointed out that the elimination of hydrogen chloride from N-chloroacetamide in the presence of alkali, actually consists of the removal of the hydrogen as a proton to form the alkali salt of N-chloroacetamide; the chloride ion is apparently released from the anion of this salt. The complete transformation may be represented by the following equations:

2 CH₃CONH₂ + Ca(OCl)₂ -> 2 CH₃CONHCl + Ca(OH)₂

2 CH₃CONHCl + Ca(OH)₂ -> (CH₃CONCl)₂Ca + 2 H₂O

(CH₃CONCl)₂Ca + 2 NaOH -> 2 (CH₃CONCl)^-Na⁺ + Ca(OH)₂

(CH₃CONCl)^-Na⁺ --Heat--> CH₃CON + NaCl --Rearr.--> CH₃N=C=O

CH₃N=C=O + H₂O + 2 NaOH -> CH₃NH₂ + Na₂CO₃

CH₃NH₂ + HCl -> CH₃NH₃⁺ Cl^-

Preparation of Methylamine Hydrochloride

The apparatus for this experiment should be set up before any materials are mixed.

A 500-mL distilling flask is fitted with a two-hole stopper carrying a thermometer and an inlet tube for air. The bulb of the thermometer should dip below the surface of the liquid, and the air tube should reach almost to the bottom of the flask. The distilling flask is attached to a condenser bearing an adapter. Two 250-mL Erlenmeyer flasks containing 35 mL each of 6 N HCl are placed in series as receivers. The first is fitted with a two-hole stopper. A glass tube attached to the adapter should dip below the surface of the HCl in the first receiver. The second receiver is connected to the first by means of another glass tube leading from above the acid solution in the first receiver to below the acid in the second.

To 16.4 g. of "H.T.H." in an Erlenmeyer flask is added 50 mL of water, and the mixture shaken until practically homogeneous. A small amount of material will remain undissolved. The solution is cooled to about 0°C in an ice-bath and 10 g. of crushed ice added.

The distilling flask is disconnected, and a cold solution of 10 g. of acetamide in 20 mL of water poured into it With the distilling flask immersed in an ice-bath, 100 g. of crushed ice is first added to the solution, followed by the addition of the cold "H.T.H." solution in three or four small portions with shaking after each addition. The temperature of the mixture should not rise above 0°C. More ice may be added to the reaction mixture if necessary. If the mixture should warm to more than 10°C (due to insufficient cooling), it should be discarded and the experiment repeated.

The flask is allowed to remain in the ice-bath for five to ten minutes. At the expiration of this time the flask is fitted to the condenser and a solution of 24 g. of NaOH in 40 mL of water at room temperature is added. The stopper is immediately replaced, and a current of air passed through the mixture during the remainder of the manipulations. The current of air should be sufficient to produce thorough mixing of the contents of the flask and to prevent bumping, yet not strong enough to cause much loss of the methylamine from the receivers.

By heating the flask the temperature of the mixture is raised rapidly to about 60°C. Between 65°C and 75°C the N-chloroacetamide decomposes with liberation of considerable heat, which, if not controlled, is likely to cause the contents of the distilling flask to bump over into the condenser. Consequently, the temperature is increased carefully from 60°C to 65°C and the flame removed. From this point the temperature will increase without the application of external heat. The current of air passing through the mixture is regulated so that it is just sufficient to prevent bumping. If the temperature rises to 80°C the flask is cooled in a bath of crushed ice and water. The temperature is held between 70°C and 80°C for five to ten minutes, or until heat is no longer spontaneously generated.

The contents of the distilling flask are then heated to boiling and distilled until 75 to 100 mL of distillate has been collected. The contents of the two receivers are combined, placed in a large evaporating dish, and evaporated over a wire gauze until the volume of the solution is about 15 mL The dish is then transferred to a water bath and the contents evaporated to dryness.

The solid residue consists of methylamine hydrochloride, together with a small amount of ammonium chloride. This product may be crystallized directly from absolute alcohol, in which case, the yield should be about seventy per cent. of the theoretical amount. It is recommended, however, that the crude product be purified according to the following procedure. The crude product is transferred to a casserole and dissolved in 15 mL of water. 10 mL of 7.5% sodium hydroxide is added and the solution heated to gentle boiling over a small flame. Since methylamine is a stronger base than ammonia, the latter, which is preferentially liberated from its hydrochloride, will be driven off with only a slight loss of methylamine. The casserole is kept in constant motion and the heating continued until all the water has evaporated and dense white fumes appear. A portion of the methylamine hydrochloride will be in the fused state. The flame is removed and the mass stirred while cooling. If the residue does not completely solidify when cold it is heated further. The residue is finely pulverized, transferred to a 250-mL Erlenmeyer flask, and refluxed a few minutes with 125 mL of absolute alcohol. A small amount of solid (NaCl) will remain undissolved. The solution is filtered through a steam funnel into a 250 mL Erlenmeyer flask. The latter is connected by means of a bent glass tube to a condenser and the alcohol distilled off until crystals begin to form in the hot liquid. The solution is then allowed to cool to room temperature and is finally cooled in an ice-bath. The crystals are filtered with suction, washed with 10 mL of absolute alcohol, and dried on a watch glass set on a hot steam coil. The yield of methylamine hydrochloride should be about 55% of the theoretical amount, melting at 228-230°C.

The use of air in this experiment serves to agitate the mixture and prevent it from bumping. If desired, a mercury-sealed mechanical stirrer may be used for this purpose and the air omitted. In this case one receiver will be sufficient. A short-stem funnel is fitted to the adapter, the larger end of the funnel dipping about 0.5 cm. below hydrochloric acid contained in a beaker. By using a mechanical stirrer the reaction may be carried out on a larger scale with no essential modification in procedure.

albert_grieves
(Stranger)
01-13-04 23:18
No 482246
      ethylamine via hoffman?

if you made propanoic acid from MEK, made ammonium propionate from that, heated it to get (propionamide?), and used that in place of acetamide in the hoffmann rearangement. Would you get ethylamine?

Rhodium
(Chief Bee)
01-13-04 23:45
No 482251
User Picture       Ethylamine synthesis

Yes, that is a theoretically sound pathway.

Reduction of acetamide would also be a way to arrive at ethylamine.

^{The Hive - Clandestine Chemists Without Borders}

albert_grieves
(Stranger)
01-14-04 18:27
No 482391
      diisopropylethylamine?

thanks for the answer, what kind of reduction HI would work?
How about diisopropyl amine from isopropyl bromide and anhydrous ammonia, converted to the propionate salt and then heated to form diisopropylpropionamide, which would undergo hoffman rearrangement to yield diisopropylethylamine for the mannich reaction
Post 481189 (josef_k: "You can use this method to use the the mannich", Newbee Forum): (I've really got fentanyl on the brain). Would the isopropyl groups interfere with the mechanics of the hoffman? thanks in advance anyone. I know it's difficult to say for sure, but even whether or not you think it would work is fine.

Rhodium
(Chief Bee)
01-14-04 21:13
No 482417
User Picture       amide reduction & hoffmann limitations

UTFSE for "amide reduction" to find various methods suitable for that procedure.

The Hoffmann rearrangement only works on primary (unsubstituted) amides, as you can infer from the reaction mechanism in the above posted article.

^{The Hive - Clandestine Chemists Without Borders}

ClearLight
(Hive Addict)
01-15-04 18:46
No 482613
      Disposal?

One question arises.. when you have that stinking mass of hypochlorite/NaCarb and residual MeNH2 wafting out of the 2 liter flask, HOW do you dispose of it???

Would really like to know that!

Infinite Radiant Light - THKRA

Psi_Locybe
(Hive Bee)
01-22-04 02:06
No 483917
      TFSE...

UTFSE for "amide reduction" to find various methods suitable for that procedure.

...since that happens to be how I stumbled here, and couldn't find much in amongst "stuff that doesn't quite tell a person what's up," I'll just post the one thread I found for the future reader...

Post 436852 (BlessTheChild: "Reducing amides to amines", Serious Chemistry)

(link edited via numeric substitution of another to remove search criteria - apologize if I screwed up)

Rev. Psi Locybe, insane alchemist.

	https://the-hive.archive.erowid.org	the-hive@erowid.org



Powered by Total Information Awareness Release 4.10.0, © 2023, Smear & Fear Asia
Links Erowid Rhodium


		ADDkid (Hive Bee) 12-26-03 21:16 No 479166				Acetamide
						Swig had some urea, and some concentrated Acetic acid, although not G.A., He then setup a clasien adapter followed by a condenser without water, Heated in reflux. He notice that ammonia smell was present very strongly (made whole room smell like urine) towards the end of the reaction. Small presence of the carbon Nitrogen salt formed inside the condenser at the very end of the rxn. Swig has read that the amide can be distilled at pure form at around 200C and most coming over at 214-216c. Swig notice that the product became very dry, and never could reach those high temp with the soild. It look like it was starting to burn or become unstabe. I failed to mention that the initial color of the urea and acetic acid was almost colorless. As the reaction proceeded, the color turn into a dark yellow. Also when trying to distill the amide, swig's "air" condenser and receiving flask filled with white crystals, which he belives is the ammonium salt, started a little above 100c. After trying to clean, Swig was left with a very soft yellow powder, which had no smell, compared to the weirld smell (almost like cookies with a ammoniua smell. Can somebody help me in trying to figure out why it is yellow. Also it is not very souble in water, with acetamide is soluble at 20c 22000g/l. P.S. I was going to try to just extract with toluene and water, since amide are neutral, it should go in the toluene layer, right. Addkid



		El_Zorro (Hive Addict) 12-26-03 22:08 No 479168				Read Eleusis's synth of acetamide.
						Read Eleusis's synth of acetamide. If remember correctly, Acetamide melts at 80C, so you just have to use a water condensor with the "cooling" water heated to 80C to keep the acetamide a liquid. Those crystals you were getting in your condesor and recieving flask were probably acetamide. It is seductive, way too seductive. -Eleusis



		Rhodium (Chief Bee) 12-27-03 21:05 No 479358				correction
						The aqueous solubility of acetamide is 200g/100mL water. ^{The Hive - Clandestine Chemists Without Borders}



		java (Hive Bee) 01-11-04 22:34 No 481890				Re: Acetamide
						While on the topic of Acetamide, "In general terms of synthesis of amides,such that they are compounds in which the -OH of the carboxylic acid has been replaced be -NH2. These are prepared by heating the ammonium salts of carboxylic acids, water driven off by destillation. RCOOH + NH3-->RCOO-NH4+-------heat---->RCONH2 + H2O In the laboratory amides are more likely to be prepared by reaction of ammonia wih acid chlorides, RCOOH----->RCOCl-----NH2---->RCONH2..." ( Ref. Organic Chemistry, Morrison & Boyd ) I noticed the reaction of Acetamide with OBr- to produce RNH2, the Hofmann Degradation (rearrangement) of amides. I noticed the source of hypobromite, and amide relatively cheap. Is there any bee with any experience making methyl amine through this procedure and assume correctly that NaOH and Br2, will work as my source of hypobromite......java Note : Edited by Java 1-12-04 We're all in this world together, http://www.aztlan.net



		Nicodem (Hive Bee) 01-12-04 09:43 No 481983				Is there any reason common bleach (NaOCl)...
						Is there any reason common bleach (NaOCl) isn't good for the Hofmann rearrangement? I always thought Br2/NaOH is used in the lab only because it is easier to dettermine the amount of Br2 than the concentration of NaOCl. Anyone knows if there are other reasons, like lower yields or else? It would sure by nice to just distill off MeNH2 from acetamide/NaOH/NaOH. Probably much better than the reduction of MeNO2. “The real drug-problem is that we need more and better drugs.” – J. Ott



		java (Hive Bee) 01-12-04 16:27 No 482029				RE: Hofmann rearrangement
						Is there any reason common bleach (NaOCl) isn't good for the Hofmann rearrangement? Nicodem ...In the lit only the -OBr will work, there's also a reaction that converts primary amines into N-halo or N,N-dihaloamines in which either the -OCl or -OBr will work here. " In the Hofmann rearrangement , an unsubstituded amide is treated with sodium hypobromite( or sodium hydroxide and bromine, which is essentially the same thing) to give a primary amine that has one carbon fewer than the starting amide,( Ref. March's 5th edition pg.1411) RCONH2 + NaOBr------>R-N=C=O------Hydrolysis---->RNH2 March's 5th edition page 819 Ref. for review, see Wallis,E.S.; Lane,J.F. Org. React. 3,267, 1946 We're all in this world together, http://www.aztlan.net



		stratosphere (Hive Bee) 01-12-04 18:54 No 482051				at a theoretical level i don't see why ...
						at a theoretical level i don't see why acetamide + hoffman wouldn't yield methylamine. another reaction you might look into is 2CH2O + NH4Cl --heat--> CH3NH2(HCl) + CH00H i can get you a reference for that rxn if you want it.



		java (Hive Bee) 01-13-04 17:06 No 482198				Re: methylamine alternative synthesis
						stratosphere, Yes , why don't you post them for the benefit of the bee's reading the forum , and please comment on your experienced with the method , if it applies ......java We're all in this world together, http://www.aztlan.net



		stratosphere (Hive Bee) 01-13-04 17:25 No 482201				i have no experience with the ...
						i have no experience with the formaldehyde+ammonium chloride method, just saw it briefly referenced in one of my organic books and thought it sounded useful, heres the ref. it gave: Gilman's Organic Synthesis I, pg. 347 yeild reported at 50%, not sure what thats relative to (perhaps theoretical yield), but with inputs that cheap it doesn't matter. im also not sure of any of the details of the reaction conditions, would be interested to see it, if someone can dig it up.



		Rhodium (Chief Bee) 01-13-04 18:51 No 482217				that synth is almost painfully well-known
						https://www.rhodium.ws/chemistry/methylamine.html ^{The Hive - Clandestine Chemists Without Borders}



		lugh (Moderator) 01-13-04 21:09 No 482237				Bee's Favorite Routes to Methylamine (Rated as: good read)
						The hypohalite route to methylamine is very well known to the bees as well, see: https://www.rhodium.ws/chemistry/eleusis/methylamine27.html and spiceboy's helpful comments in Post 108635 (dormouse: "Methylamine via hoffman -Molly Heart", Novel Discourse) and the article by Hauser et al from JCE 14 542-4 (1937) Chemistry is our Covalent Bond



		Rhodium (Chief Bee) 01-13-04 22:38 No 482241				Methylamine HCl from Acetamide (Rated as: excellent)
						An Elementary Laboratory Experiment Involving the Hofmann Rearrangement: The Preparation of Methylamine Hydrochloride from Acetamide by Means of Calcium Hypochlorite C. R. Hauser and W. B. Renfrow, Jr. Journal of Chemical Education 12, 542-544 (1937) (https://www.rhodium.ws/chemistry/methylamine.acetamide.html) The well-known Hofmann reaction by which, an amide, in the presence of chlorine or bromine and an alkali, is converted into a primary amine with one less carbon atom, is of considerable interest in organic chemistry. The reaction may be used in going "down series," and it serves as a laboratory method for the preparation of a primary aliphatic amine. The reaction is of interest also because it involves a molecular rearrangement. The Hofmann reaction is often illustrated in the laboratory by the preparation of methylamine hydrochloride from acetamide. It has been our experience,however, that when this experiment is carried out with bromine and alkali according to the directions given in many laboratory manuals, a considerable portion of the product consists of ammonium chloride. In this paper directions are given for the preparation of methylamine hydrochloride from acetamide using commercial calcium hypochlorite and sodium hydroxide. The product obtained with these reagents is contaminated with only a small amount of ammonium chloride, and this can be removed by treatment with aqueous alkali as described below. In this experiment, acetamide is first converted into N-chloroacetamide, which, in the presence of alkali, eliminates hydrogen chloride and undergoes rearrangement to form methylisocyanate. Hydrolysis of the latter gives methylamine which is isolated as the hydrochloride. It should be pointed out that the elimination of hydrogen chloride from N-chloroacetamide in the presence of alkali, actually consists of the removal of the hydrogen as a proton to form the alkali salt of N-chloroacetamide; the chloride ion is apparently released from the anion of this salt. The complete transformation may be represented by the following equations: 2 CH₃CONH₂ + Ca(OCl)₂ -> 2 CH₃CONHCl + Ca(OH)₂ 2 CH₃CONHCl + Ca(OH)₂ -> (CH₃CONCl)₂Ca + 2 H₂O (CH₃CONCl)₂Ca + 2 NaOH -> 2 (CH₃CONCl)^-Na⁺ + Ca(OH)₂ (CH₃CONCl)^-Na⁺ --Heat--> CH₃CON + NaCl --Rearr.--> CH₃N=C=O CH₃N=C=O + H₂O + 2 NaOH -> CH₃NH₂ + Na₂CO₃ CH₃NH₂ + HCl -> CH₃NH₃⁺ Cl^- Preparation of Methylamine Hydrochloride The apparatus for this experiment should be set up before any materials are mixed. A 500-mL distilling flask is fitted with a two-hole stopper carrying a thermometer and an inlet tube for air. The bulb of the thermometer should dip below the surface of the liquid, and the air tube should reach almost to the bottom of the flask. The distilling flask is attached to a condenser bearing an adapter. Two 250-mL Erlenmeyer flasks containing 35 mL each of 6 N HCl are placed in series as receivers. The first is fitted with a two-hole stopper. A glass tube attached to the adapter should dip below the surface of the HCl in the first receiver. The second receiver is connected to the first by means of another glass tube leading from above the acid solution in the first receiver to below the acid in the second. To 16.4 g. of "H.T.H." in an Erlenmeyer flask is added 50 mL of water, and the mixture shaken until practically homogeneous. A small amount of material will remain undissolved. The solution is cooled to about 0°C in an ice-bath and 10 g. of crushed ice added. The distilling flask is disconnected, and a cold solution of 10 g. of acetamide in 20 mL of water poured into it With the distilling flask immersed in an ice-bath, 100 g. of crushed ice is first added to the solution, followed by the addition of the cold "H.T.H." solution in three or four small portions with shaking after each addition. The temperature of the mixture should not rise above 0°C. More ice may be added to the reaction mixture if necessary. If the mixture should warm to more than 10°C (due to insufficient cooling), it should be discarded and the experiment repeated. The flask is allowed to remain in the ice-bath for five to ten minutes. At the expiration of this time the flask is fitted to the condenser and a solution of 24 g. of NaOH in 40 mL of water at room temperature is added. The stopper is immediately replaced, and a current of air passed through the mixture during the remainder of the manipulations. The current of air should be sufficient to produce thorough mixing of the contents of the flask and to prevent bumping, yet not strong enough to cause much loss of the methylamine from the receivers. By heating the flask the temperature of the mixture is raised rapidly to about 60°C. Between 65°C and 75°C the N-chloroacetamide decomposes with liberation of considerable heat, which, if not controlled, is likely to cause the contents of the distilling flask to bump over into the condenser. Consequently, the temperature is increased carefully from 60°C to 65°C and the flame removed. From this point the temperature will increase without the application of external heat. The current of air passing through the mixture is regulated so that it is just sufficient to prevent bumping. If the temperature rises to 80°C the flask is cooled in a bath of crushed ice and water. The temperature is held between 70°C and 80°C for five to ten minutes, or until heat is no longer spontaneously generated. The contents of the distilling flask are then heated to boiling and distilled until 75 to 100 mL of distillate has been collected. The contents of the two receivers are combined, placed in a large evaporating dish, and evaporated over a wire gauze until the volume of the solution is about 15 mL The dish is then transferred to a water bath and the contents evaporated to dryness. The solid residue consists of methylamine hydrochloride, together with a small amount of ammonium chloride. This product may be crystallized directly from absolute alcohol, in which case, the yield should be about seventy per cent. of the theoretical amount. It is recommended, however, that the crude product be purified according to the following procedure. The crude product is transferred to a casserole and dissolved in 15 mL of water. 10 mL of 7.5% sodium hydroxide is added and the solution heated to gentle boiling over a small flame. Since methylamine is a stronger base than ammonia, the latter, which is preferentially liberated from its hydrochloride, will be driven off with only a slight loss of methylamine. The casserole is kept in constant motion and the heating continued until all the water has evaporated and dense white fumes appear. A portion of the methylamine hydrochloride will be in the fused state. The flame is removed and the mass stirred while cooling. If the residue does not completely solidify when cold it is heated further. The residue is finely pulverized, transferred to a 250-mL Erlenmeyer flask, and refluxed a few minutes with 125 mL of absolute alcohol. A small amount of solid (NaCl) will remain undissolved. The solution is filtered through a steam funnel into a 250 mL Erlenmeyer flask. The latter is connected by means of a bent glass tube to a condenser and the alcohol distilled off until crystals begin to form in the hot liquid. The solution is then allowed to cool to room temperature and is finally cooled in an ice-bath. The crystals are filtered with suction, washed with 10 mL of absolute alcohol, and dried on a watch glass set on a hot steam coil. The yield of methylamine hydrochloride should be about 55% of the theoretical amount, melting at 228-230°C. The use of air in this experiment serves to agitate the mixture and prevent it from bumping. If desired, a mercury-sealed mechanical stirrer may be used for this purpose and the air omitted. In this case one receiver will be sufficient. A short-stem funnel is fitted to the adapter, the larger end of the funnel dipping about 0.5 cm. below hydrochloric acid contained in a beaker. By using a mechanical stirrer the reaction may be carried out on a larger scale with no essential modification in procedure.



		albert_grieves (Stranger) 01-13-04 23:18 No 482246				ethylamine via hoffman?
						if you made propanoic acid from MEK, made ammonium propionate from that, heated it to get (propionamide?), and used that in place of acetamide in the hoffmann rearangement. Would you get ethylamine?



		Rhodium (Chief Bee) 01-13-04 23:45 No 482251				Ethylamine synthesis
						Yes, that is a theoretically sound pathway. Reduction of acetamide would also be a way to arrive at ethylamine. ^{The Hive - Clandestine Chemists Without Borders}



		albert_grieves (Stranger) 01-14-04 18:27 No 482391				diisopropylethylamine?
						thanks for the answer, what kind of reduction HI would work? How about diisopropyl amine from isopropyl bromide and anhydrous ammonia, converted to the propionate salt and then heated to form diisopropylpropionamide, which would undergo hoffman rearrangement to yield diisopropylethylamine for the mannich reaction Post 481189 (josef_k: "You can use this method to use the the mannich", Newbee Forum): (I've really got fentanyl on the brain). Would the isopropyl groups interfere with the mechanics of the hoffman? thanks in advance anyone. I know it's difficult to say for sure, but even whether or not you think it would work is fine.



		Rhodium (Chief Bee) 01-14-04 21:13 No 482417				amide reduction & hoffmann limitations
						UTFSE for "amide reduction" to find various methods suitable for that procedure. The Hoffmann rearrangement only works on primary (unsubstituted) amides, as you can infer from the reaction mechanism in the above posted article. ^{The Hive - Clandestine Chemists Without Borders}



		ClearLight (Hive Addict) 01-15-04 18:46 No 482613				Disposal?
						One question arises.. when you have that stinking mass of hypochlorite/NaCarb and residual MeNH2 wafting out of the 2 liter flask, HOW do you dispose of it??? Would really like to know that! Infinite Radiant Light - THKRA



		Psi_Locybe (Hive Bee) 01-22-04 02:06 No 483917				TFSE...
						UTFSE for "amide reduction" to find various methods suitable for that procedure. ...since that happens to be how I stumbled here, and couldn't find much in amongst "stuff that doesn't quite tell a person what's up," I'll just post the one thread I found for the future reader... Post 436852 (BlessTheChild: "Reducing amides to amines", Serious Chemistry) (link edited via numeric substitution of another to remove search criteria - apologize if I screwed up) Rev. Psi Locybe, insane alchemist.

All 18 posts	End of thread	Top