p-alkoxyphenol writeup

[Vitus_Verdegast]

Found the following note lying on the floor in a bus station:

Preparation of p-MeO-phenol.

This is essentially repeating the work of our fellow bee Antoncho, but the end product was purified by means of vacuum distillation.

220 ml methanol was added to a 1L beaker and magnetic stirring was commenced. To this was added, in 5 ml aliquots, 40 ml conc. H₂SO₄. The solution was allowed to cool to RT, and there was added 40 grams of hydroquinone followed by 4 gr p-benzoquinone.
The mixture was left stirring for 20 hours and acidified with 15% H₂SO₄. No NaCl was available for the moment, so a conc. Na₂SO₄ solution was added, followed by extracting 3x with toluene. The pooled extracts were washed with a little water, and the solvent evaporated in vacuo. The p-MeO-phenol came over at 120° at the fridge pump (bp. 243°). Use warm water in the condensor, as the p-MeO-phenol instantly solidifies and plugs the whole thing. For the same reason the recieving end was warmed when necessary. This yielded 14 gr of white p-MeO-phenol with here and there a purple spot, leaving in the distillation flask a black tarry residue that is only sparingly soluble in hot water and conc Na₂CO₃-sol. Methanol removed some of it.

The first time I performed this reaction I got a much better yield, why is it now so crappy? Could it be because I used Na₂SO₄ instead of NaCl (and not fully extracting p-MeO-phenol) ?


p-EtO-phenol and the Reimer-Tiemann will follow.

[Antoncho]

Add more sulfuric. Like, twice as much.

I don't have the exact numbers but i remember that SWIM once added an amt of acid exceeding that in the patent (the cold way) and got ~92% yield of dirty phenol.


Other notes:

1) p-EtO-phenol will probably give you ~40% yield (see the patent)

2) Reimer-Tiemann on it is most likely to fail (see "A patented improvent" post of mine - the patent mentioned in there)



Antoncho

P.S. Good luck!

[Vitus_Verdegast]

When hydroquinone monoethyl ether was formylated under the conditions of the process in accordance with the present invention, the corresponding end product was obtained in a very low yield.

Maybe Friedel-Craft would be an option then? (I really like the one with p-toluenesulfonic acid and the Dean-Stark trap)

I couldn't find anything on the 5-EtO homologue in PiHKaL, and no active level is yet known for the 2,5-diEtO homologue  

[Antoncho]

>Maybe Friedel-Craft would be an option then? (I really like the one with p-toluenesulfonic acid and the Dean-Stark trap)

Well, the only way is to try it and see if it works.


>I couldn't find anything on the 5-EtO homologue in PiHKaL, and no active level is yet known for the 2,5-diEtO homologue


They are there. Look for Tweetios.




Antoncho

[Vitus_Verdegast]

I found this:

There are two "Tweetios" known that are related to 2C-B.  (See recipe #23 for the origin of this phrase.)  The 2-EtO- homologue of 2C-B is 4-bromo-2-ethoxy-5-methoxyphenethylamine, or 2CB-2ETO.  The unbrominated benzaldehyde (2-ethoxy-5-methoxybenzaldehyde) had a melting point of 47.5-48.5 deg C, the unbrominated nitrostyrene intermediate a melting point of 76-77 deg C, and the final hydrochloride a melting point of 185-186 deg C.  The hydrobromide salt had a melting point of 168.5-169.5 deg C.  It seems that one gets about as much effect
as can be had, with a dosage of about 15 milligrams, and increases above this, to 30 and to 50 milligrams merely prolong the activity (from about 3 hours to perhaps 6 hours).  At no dose was there an intensity that in any way resembled that of 2C-B.

The 2,5-DiEtO- homologue of 2C-B is 4-bromo-2,5-diethoxyphenethylamine, or 2CB-2,5-DIETO.  The unbrominated impure benzaldehyde (2,5-diethoxybenzaldehyde) had a melting point of about 57 deg C, the unbrominated impure nitrostyrene intermediate a melting point of about 60 deg C, and the final hydrochloride a melting point of 230-231 deg C.  The hydrobromide salt had a melting point of 192-193 deg C.  At levels of 55 milligrams, there was only a restless sleep, and strange dreams.  The active level is not yet known.

and this:

in general,   2-EtO    : shorter duration, lower activity
              5-EtO    : relatively unchanged potency
            2,5-di-EtO : very weak if active at all

[demorol]

...and there was added 40 grams of hydroquinone followed by 4 gr p-benzoquinone.

I can't figure out what is the purpose of added benzoquinone. If anybody knows, please, tell me.

[Vitus_Verdegast]

Read

Post 267698

(Antoncho: "P-MeO-phenol from hydroquinone: part II", Novel Discourse)

It is thought that benzoquinone in acidic methanol forms an unstable hemiketal, which reacts immediately with hydroquinone to form benzoquinone and hydroquinone monomethyl ether. The benzoquinone is thus regenerated and is able to form more hemiketal.

[Vitus_Verdegast]

220 ml 95% ethanol was added to a 1L beaker and magnetic stirring was commenced. To this was added, in 5 ml aliquots, 40 ml conc. H2SO4. The solution was allowed to cool to RT, and there was added 30 grams of hydroquinone followed by 3 gr p-benzoquinone.
The mixture was left stirring for 26 hours and acidified with 15% H2SO4. Some brine was added, followed by solid NaCl and extracting 4x with toluene. The solvent was evaporated in vacuo.

SWIM should have washed his organic layer with water of course, to get the traces of acid out, but he forgot .

So an attempt at vacuum distilling was made, but only a gram or so of purple    material was obtained when the boiling stopped and it was clear to SWIM that the stuff had carbonized. That flask is going to be a bitch to clean.       

Well, that'll teach him to always pay full attention next time.

some notes:

- SWIM makes his alkyl hydrogen sulfate as stated in

Post 256342

(Antoncho: "Methylation of hydroquinone w/NaMeSO4: good news!", Novel Discourse) but uses MgSO₄ instead of Na₂SO₄.

- Toluene is probably not the best extraction solvent to use. After the fourth extraction the layer is still very dark. Next time SWIM will use DCM.

- One might consider taking precautions as to not letting your skin come in contact with p-MeO-phenol. It is melanocytotoxic, which means that it causes loss of pigment and skin allergy.
Read for more info

http://www.ispb.ro/conferinta/engleza/occupational_vitiligo.htm

[GC_MS]

2-methoxy-phenol

55 g (0.5 mol) pyrocatechol is dissolved in 100 mL nitrobenzene under stirring. With intervals of 10 minutes and on a waterbath at 40°C, three portions of 21 mL dimethylsulfate (0.65 mol together) are added. The pH should be 8-9 and is obtained by the dropwise addition of 20% NaOH (about 100-110 mL, check with Spezialindikatorpapier 8.2-10). Strong stirring is necessary due to the strong exothermic reaction. The methylation reaction has finished after 2 - 2.5 hours. The pH should remain stable if no further NaOH solution is added. The isolated yield of 2-methoxyphenol is 55 g, or 90% of theory (bp: 199-201°C).

1,2-dimethoxy-benzene

11 g pyrocatechol is dissolved in 50 mL 20% NaOH solution. The solution colours brown and 20 mL dimethylsulfate is added while stirring firmly. The solution becomes very warm and, after having allowed the solution to cool down, the veratrol (1,2-dimethoxy-benzene) is extracted with ether. The ether is removed by distillation and the residue crystallizes spontaneously. The result is long crystalline needles, mp 31°C, bp 205°C. Yield: 11.5 g.

Both procedures have been taken out the Houben-Weyl. Sorry, but I didn't write down the exact volume nor references at the time. You'll have to take my word for it.
So Vit, hope you find something useful in these procedures. I usually base all my methylation reactions on these procedures.

[Mountain_Girl]

VV,

I have been intimate with p-meo phenol. Repeatedly.
I have no diseases or allergies but I have picked up a few other things:

The mixture was left stirring for 20 hours and acidified with 15% H₂SO₄

I usually just reflux for ~5 hrs and it seems to do the trick. I would agree with Antoncho that much more H2SO4 should be used (roughly the same mass as hydroquinone IIRC). This would make your later acidification step unecessary as well.

Because the final reaction medium is already so acidic I don't believe that adding a salt in the extraction step will make much of an improvement to recovery of product. But then I usually add water and distill off most of the MeOH first. I stand to be corrected on this maybe...

extracting 3x with toluene

I've tried DCM, Dichloroethane and xylene. DCM is the best for sure (good solvent for product, denser than water, low bp).

p-benzoquinone

If you have easy access to benzoquinone, it's probably the best to use. Otherwise quinhydrone also works.
Since both of these compounds can be prepared from hydroquinone, it is then natural to consider the possibility of forming the catalyst in situ.

I've tried this by adding H₂O₂ to the reaction mixture (before and after H₂SO₄ addition, dripped in, all in one amount, different permutations).
Result: It does work but it seems to make a lot of tar and the final solution is so dark that it is extremely difficult to see the interphase between the two layers during the extraction step.
So in conclusion, it's not worth it IMO.
However, there is still some room for experimenation here. You could try adding some I₂ or perhaps another oxidant (eg. MnO₂), etc.

Use warm water in the condensor, as the p-MeO-phenol instantly solidifies and plugs the whole thing

Here is where I still encounter major problems. If I use cold water in the condensor or no water at all, at no point do I see liquid p-meo phenol. It seems to only collect as a solid in all the bends and constrictions in the apparatus. I then have to keep stopping the process and washing all the blockages out with acetone - a very tedious process (but the snow white product is achingly beautiful I must admit...). It seems that the gas velocity is too high or something, and I think I lose some product into my pump. I'll try warm water in the condensor.
Anyhow, still working on this.

[Mountain_Girl]

Collected love letters from my affair with p-Meo-Phenol:

95:61763
Hydroquinone monomethyl ether.
Pokrovskaya, I. E.; Parbuzina, I. L.; Gubenko, I. I. (USSR ).  U.S.S.R. SU 825487 30 Apr 1981  From: Otkrytiya, Izobret., Prom. Obraztsy, Tovarnye Znaki 1981, (16), 93.  (Russian). (Union of Soviet Socialist Republics).  CODEN: URXXAF.  CLASS: IC: C07C043-205; C07C041-01.  APPLICATION: SU 76-2412080 761014.  DOCUMENT TYPE: Patent CA Section: 25 (Noncondensed Aromatic Compounds)
Hydroquinone (I) mono-Me ether was prepd. by treating I with a neutral soda mixt. of MeOH and H2SO4 at 90-100°.  In an improved procedure, the reaction was carried out in the presence 4-10 wt.% I di-Me ether, which was recycled.

95:61658
Methylation of hydroquinone.
Bebikh, G. F.; Parguzina, I. L.; Gubenko, A. S. (USSR).  Vestn. Mosk. Univ., Ser. 2:  Khim., 22(2), 200-3 (Russian) 1981.  CODEN: VMUKA5.  ISSN: 0579-9384.  DOCUMENT TYPE: Journal CA Section: 25 (Noncondensed Aromatic Compounds)
Methylation of hydroquinone with MeOH to give 4-MeOC6H4OH was carried out over KU-2-8, KOAc, or NaOAc; data for a no. of runs over a range of temps. (100-300°) and pressures (10-30 atm) were given.  Best yields of 4-MeOC6H4OH were obtained in 4 h at 300°.

94:191922
N-Methoxyphenol.
Kolenko, I. P.; Ilatovskii, R. E.; Kharchuk, V. G.; Ignat'eva, I. S.; Ermolaev, A. V.; Rozanov, S. G.; Vostretsov, V. P. (Ural Institute of Chemistry;  Bolokhovo Chemical Combine, USSR).  U.S.S.R. SU 793980 30 Dec 1981  From: Otkrytiya, Izobret., Prom. Obraztsy, Tovarnye Znaki 1981, (1), 90-1.  (Russian). (Union of Soviet Socialist Republics).  CODEN: URXXAF.  CLASS: IC: C07C043-20.  APPLICATION: SU 78-2714139 13 Dec 1978.  DOCUMENT TYPE: Patent CA Section: 25 (Noncondensed Aromatic Compounds)
The title substance was prepd. with increased selectivity by methylation of 1,4-dihydroxybenzene with MeOH in H2O (1:3-5:30-50 mol ratio) at 250-350°, 1-75 atm pressure using a catalyst consisting of A1 silicate contg. 87-88 SiO2, 10-11 Al2O3, and 1.5-2 wt.% other metal in H form

93:71276
Preparation of hydroquinone ethers.
Bellas, Michael; Cahill, Robert; Hayes, Leslie (Kodak Ltd., Engl.).  Brit. GB 1557237 5 Dec 1979, 8 pp.  (English). (United Kingdom).  CODEN: BRXXAA.  CLASS: IC: C07C041-00.  APPLICATION: GB 76-22999 3 Jun 1976.  DOCUMENT TYPE: Patent CA Section: 25 (Noncondensed Aromatic Compounds)
CGM057994
The title ethers I [R = C1-18 alkyl, (CH2)2OEt; R1 = H, C1-4 alkyl] were prepd. by reaction of a mixt. of the corresponding hydroquinone and benzoquinone (wt. ratio 5:1 to 20:1) with ROH in the presence of an acid dehydration catalyst.  E.g., reaction of 0.67 g benzoquinone and 9.33 g hydroquinone with 50 mL MeOH in the presence 10 g concd. H2SO4 gave 80% I (R = Me, R1 = H).

1:140564
Hydroquinone monoalkyl ethers.
(Eastman Kodak Co., USA).  Jpn. Kokai Tokkyo Koho JP 54061132 17 May 1979 Showa, 4 pp.  (Japanese). (Japan).  CODEN: JKXXAF.  CLASS: IC: C07C043-22; B01J027-02; B01J031-10; C07C043-20.  APPLICATION: JP 77-119876 5 Oct 1977.  DOCUMENT TYPE: Patent CA Section: 25 (Noncondensed Aromatic Compounds)
CGM091271
Ethers I (R = alkyl, R1 = H, alkyl; R2 = R3 = H or R2R3 = CH:CHCH:CH) were prepd. by esterification of I (R = H; R1 - R3 as above) with alcs. ROH in the presence of benzoquinones II (R1 - R3 as above) and acidic dehydrating agents.  Thus, stirring I (R - R3 = H) in MeOH with benzoquinone and H2SO4 16 h gave 100% I (R = Me, R1 - R3 = H).

90:168271
p-Methoxyphenol.
Gubenko, I. I.; Kondrashova, M. F.; Manyashkina, V. M.; Medvedeva, S. P.; Parbuzina, I. L. (USSR ).  U.S.S.R. SU 643489 25 Jan 1979  From: Otkrytiya, Izobret., Prom. Obraztsy, Tovarnye Znaki 1979, (3), 84.  (Russian). (Union of Soviet Socialist Republics).  CODEN: URXXAF.  CLASS: IC: C07C043-22.  APPLICATION: SU 75-2146487 19 Jul 1975.  DOCUMENT TYPE: Patent CA Section: 25 (Noncondensed Aromatic Compounds)
P-MeOC6H4OH was prepd. by methylating hydroquinone with MeOH-H2SO4-Na2CO3 (1.3:1:1) at 90-100°.

89:208651
Solvent composition effects in reversed phase partition chromatography.  I.  Phenols in systems of the type oleyl alcohol-water + acetone or water + acetonitrile.
Soczewinski, Edward; Waksmundzka-Hajnos, Monika (Inst. Basic Chem. Sci., Acad. Med. Lublin, Lublin, Pol.).  Chem. Anal. (Warsaw), 23(3), 429-35 (English) 1978.  CODEN: CANWAJ.  DOCUMENT TYPE: Journal CA Section: 80 (Organic Analytical Chemistry)
The relation between RM values of 28 phenols and the concn. of Me2CO or MeCN in the aq. mobile phase was investigated; the stationary phase was Whatman no. 4 paper impregnated with C6H6 solns. of oleyl alc.  In most cases the relations were linear, which permitted the detn. of the RM values beyond the range of optimum accuracy by extrapolation

105:104738
Electrochemical synthesis of hydroquinone monoalkyl ethers.
Takamatsu, Hideki; Takakuwa, Yasuo; Tsuchiya, Shuji (Nissan Chemical Industries, Ltd., Japan).  Jpn. Kokai Tokkyo Koho JP 61064891 A2 3 Apr 1986 Showa, 4 pp.  (Japanese). (Japan).  CODEN: JKXXAF.  CLASS: ICM: C25B003-10.  APPLICATION: JP 84-185427 6 Sep 1984.  DOCUMENT TYPE: Patent CA Section: 72 (Electrochemistry) Section cross-reference(s): 25
Hydroquinones and alcs. are electrolyzed for monoalkylation to give hydroquinone monoalkyl ethers.  The ethers, useful as intermediates for medicines, agrochems., dyes, etc., are obtained selectively at high yield.  Thus, hydroquinone and was dissolved in EtOH and electrolyzed, using Pt electrodes, for 18 h at 30 V and ~30° (12,000 C electricity) to give hydroquinone monoethyl ether at 86% conversion, 99% selectivity, and 85% yield.  No byproduct (hydroquinone di-Et ether) was obtained.

104:87782
Study of the steam distillation of phenolic compounds using ultraviolet spectrometry.
Norwitz, George; Nataro, Nicole; Keliher, Peter N. (Dep. Chem., Villanova Univ., Villanova, PA 19085, USA).  Anal. Chem., 58(3), 639-41 (English) 1986.  CODEN: ANCHAM.  ISSN: 0003-2700.  DOCUMENT TYPE: Journal CA Section: 21 (General Organic Chemistry)
The steam distn. of 42 phenolic compds. was studied using a semimicro steam-distn. app. and UV spectrometry.  In the distn., the following gave >95% recoveries: PhOH, 2-RC6H4OH (R = O2N, MeO, Br, Cl), 2,3- and 2,4-Cl2C6H3OH, 2,4,5- and 2,4,6-Cl3C6H2OH, 2,4-Br2C6H3OH, 2-, 3- and 4-cresol, 4,2-Cl(Me)C6H3OH, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-xylenol, 4-RCMe2C6H4OH (R = Me, Et), thymol and carvacrol.  The percent recovery for the other phenolic compds. was as follows: 3-O2NC6H4OH, 3.7%; 4-O2NC6H4OH, 1.8%; 3-MeOC6H4OH, 31.1; 4-MeOC6H4OH, 23.2; 3-BrC6H4OH, 79.6; 4-BrC6H4OH, 67.8; 3-ClC6H4OH, 93.5; 4-ClC6H4OH, 91.6; 3,4-Cl2C6H3OH, 64.1; 2,4-(O2N)2C6H3OH, 21.2; picric acid, 0.0; 2-H2NC6H4OH, 0.1; 3-H2NC6H4OH, 0.2; 4-H2NC6H4OH, 0.1; pyrocatechol, 1.6; resorcinol, 0.4; hydroquinone (I), 0.0; pyrogallol, 0.7; and phloroglucinol, 0.1.  Examg. the spectra of the undistd., distd. and residual solns. showed that the aminophenols undergo some decompn., and that I is almost completely destroyed during the distn.  The important role that H bonding (intermol. and intramol.) plays in the recovery from steam distn. is examd

97:91924
Monoalkyl ethers of hydroquinone and its derivatives.
Rivetti, Franco; Romano, Ugo; Di Muzio, Nicola (Anic S.p.A., Italy).  Ger. Offen. DE 3145212 A1 19 May 1982, 14 pp.  (German). (Germany).  CODEN: GWXXBX.  CLASS: IC: C07C043-23; C07C041-09.  APPLICATION: DE 81-3145212 13 Nov 1981.  PRIORITY: IT 80-25933 13 Nov 1980; IT 80-25934 13 Nov 1980.  DOCUMENT TYPE: Patent CA Section: 25 (Benzene, Its Derivatives, and Condensed Benzenoid Compounds)
CGM140896
The title compds. I (R = alkyl, R1 = H, alkyl) were prepd. by treating a hydroquinone I (R = H) with ROH in the presence of a transition metal salt.  A mixt. of 1,4-(HO)2C6H4, MeOH, and CuCl2 under N2 kept 2.5-4 h at 105° gave I (R = Me, R1 = H) in 87% selectivity with 55-85% conversion.  Little or no etherification occurred in the absence of CuCl2

112:136225
Defense mechanisms of arthropods.  Part 91.  p-Methoxyphenol:  chemical basis of stench of a female butterfly.
Eisner, T.; Eisner, M.; Jaouni, T.; Fales, H. M. (Sect. Neurobiol. Behavior, Cornell Univ., Ithaca, NY 14853, USA).  Naturwissenschaften, 77(1), 33 (English) 1990.  CODEN: NATWAY.  ISSN: 0028-1042.  DOCUMENT TYPE: Journal CA Section: 12 (Nonmammalian Biochemistry)
The female Great Southern White butterfly (Ascia manuste phileta) emits a potent phenolic stench when disturbed.  The odor stems from a pasty secretion from the genitalia.  Gas chromatog./mass spectrometry identified this defensive compd. as p-methoxyphenol.

106:226806
Steam distillation of phenolic compounds in the presence of a large amount of sodium chloride.
Norwitz, George; Nataro, Nicole; Keliher, Peter N. (Dep. Chem., Villanova Univ., Villanova, PA 19085, USA).  Microchem. J., 35(2), 240-3 (English) 1987.  CODEN: MICJAN.  ISSN: 0026-265X.  DOCUMENT TYPE: Journal CA Section: 80 (Organic Analytical Chemistry) Section cross-reference(s): 61
The steam distn. of phenolic compds. in the presence of a large amt. of NaCl was studied by use of a semimicro steam distn. app. and UV spectrometry.  The recovery of many phenolic compds. in steam distn. was improved by the addn. of the NaCl, particularly in the case of 3- and 4-methoxyphenol, 3- and 4-bromophenol, and 3- and 4-chlorophenol (essentially complete recovery was obtained with the latter four compds.).  The recovery with 2-chlorophenol was ~5% lower.  The recovery with 2-nitrophenol was ~10% lower and the results tended to be erratic (probably because the NaCl affects the intramol. H bonding of this polar compd.).  The addn. of NaCl did not improve the very low recoveries obtained with aminophenols and di- and trihydroxyphenols without NaCl.  It is recommended that NaCl be used in the detn. of total phenolic compds. in waters in procedures that require a steam distn., since more complete recovery is obtained for the phenolic compds. that are likely to be found in waters.

[Mountain_Girl]

125:167560
Preparation of 4-alkoxyphenols from 1,4-dihydroxybenzene.
Saito, Toranosuke; Hirayama, Takumi; Sakaguchi, Shigeo (Sanko Kaihatsu Kagaku Kenk, Japan).  Jpn. Kokai Tokkyo Koho JP 08151343 A2 11 Jun 1996 Heisei, 5 pp. (Japan).  CODEN: JKXXAF.  CLASS: ICM: C07C043-23.  ICS: B01J027-06; B01J031-02; C07C041-09.  ICA: C07B061-00.  APPLICATION: JP 94-294775 29 Nov 1994.  DOCUMENT TYPE: Patent CA Section: 25 (Benzene, Its Derivatives, and Condensed Benzenoid Compounds) Section cross-reference(s): 35
4-HOC6H4OR (I; R = lower alkyl), useful as polymn. inhibitors for vinyl monomers, stabilizers for polyesters, and intermediates for drugs, agrochems, and, dyes are prepd. by addn. of H2O2 to a mixt. of 1,4-C6H4(OH)2 (II), ROH, and ³1 of I, HI, metal iodides, and alkali metal iodates followed by addn. of acid catalysts or by addn. of H2O2 to a mixt. of II, ROH, ³1 of HI, metal iodides, and alkali metal iodates, and acid catalysts.  An aq. H2O2 soln. was added dropwise to a mixt. of II, MeOH, H2SO4, and I at 60° over 3 h and the reaction mixt. was further stirred at 60-70° for 6 h to give a product contg. 87.3% I (R = Me), vs. 54% for a control using no I.

125:86240
Methods for the preparation of hydroquinone monomethyl ether.
Teng, Dianhua; Li, Tongzhen; Ma, Shuqin (Inst. Petrochem., Heilongjiang Acad. Scis., Harbin 150040, Peop. Rep. China).  Huaxue Yu Nianhe, (2), 105-106 (Chinese) 1996.  CODEN: HYZHEN.  ISSN: 1001-0017.  DOCUMENT TYPE: Journal; General Review CA Section: 25 (Benzene, Its Derivatives, and Condensed Benzenoid Compounds)
A review with 9 refs. on different methods for prepn. of hydroquinone monomethyl ether with the emphasis on the methods using hydroquinone and methanol as raw materials, an acid as catalyst, and benzoquinone as co-catalyst

124:260570
Process for the preparation of hydroquinone monoalkyl ethers.
Caproiu, Miron Teodor; Banciu, Anca Adriana; Olteanu, Emilia (Combinatul Petrochimic, Pitesti, Rom.).  Rom. RO 105090 B1 1 Nov 1994, 5 pp. (Romania).  CODEN: RUXXA3.  CLASS: ICM: C07C043-115.  APPLICATION: RO 89-143326 18 Dec 1989.  DOCUMENT TYPE: Patent CA Section: 25 (Benzene, Its Derivatives, and Condensed Benzenoid Compounds)
The title ethers were prepd. by treating hydroquinone with an alc. in presence of an oxidizing agent and a dehydrating agent in the alc. as solvent, or using another solvent.  Thus, hydroquinone was treated with MeOH, H2O2, and H2SO4 under reflux for 6 h to give 70.5% 4-HOC6H4OMe of 98.7% purity.

121:270800
Effect of substituted groups on the retention of monosubstituted phenols in reversed-phase liquid chromatography.
Kim, Hoon-Joo; Lee, In-Ho; Lee, Dai Woon (Anal. Sci., R and D Cent., Daejeon 305-343, S. Korea).  J. Korean Chem. Soc., 38(, 562-9 (Korean) 1994.  CODEN: JKCSEZ.  ISSN: 1017-2548.  DOCUMENT TYPE: Journal CA Section: 80 (Organic Analytical Chemistry) Section cross-reference(s): 22
The retention data of twenty one monosubstituted phenols in the eluent systems contg. 30-70% of methanol or acetonitrile as org. modifiers, on C18 and Ph columns were collected to study the effect of the substituted groups on the retention of phenols.  The capacity factors of the solutes except amino phenols are greater on C18 than on Ph column.  And all the solutes showed greater capacity factors in methanol-water than that in acetonitrile-water as a mobile phase.  Generally the elution order between meta and para isomers of monosubstituted phenols in consistent (p < m) regardless of the polarity of the substituted group.  But the elution order between ortho and meta isomers of phenol varies with regard to the polarity of the substituted group.  The retention of the monosubstituted phenols was influenced by the interaction between the solute and unreacted silanol of columns as well as the interaction between the solute and C18 or Ph group of columns.  The effect of unreacted silanol on the retention of the monosubstituted phenols is greater on C18 than on Ph column.  The greater hydrogen bonding acceptor basicity(b) of the substituted group is, the greater this effect is.  The relation between the retention of the monosubstituted phenols and their parameters such as van der Waals vol. (VWV) and hydrogen bonding acceptor basicity(b) was studied.  The good linearity was obsd. in the plot log k' vs. (1.1VWV/100-1.84b).  In consequence, the retention of the monosubstituted phenols on C18 and Ph columns can be easily predicted by the parameter (1.01VWV/100-1.84b)

118:124199
Etherification of phenols with lower alcohols.
Uohama, Misao; Takahashi, Katsuji (Dainippon Ink and Chemicals, Inc., Japan).  Jpn. Kokai Tokkyo Koho JP 04305546 A2 28 Oct 1992 Heisei, 6 pp. (Japan).  CODEN: JKXXAF.  CLASS: ICM: C07C043-205.  ICS: B01J023-24; B01J027-02; B01J027-188; B01J031-02; C07C041-01; C07C043-23.  ICA: C07B061-00.  APPLICATION: JP 91-67436 30 Mar 1991.  DOCUMENT TYPE: Patent CA Section: 25 (Benzene, Its Derivatives, and Condensed Benzenoid Compounds)
Phenols are etherified with lower alcs. in liq. phases in the presence of acid catalysts with removing alkyl ethers together with unreacted alcs. and H2O by distn.  Catechol and concd. H2SO4 were heated at 150° with adding MeOH-catechol mixt. for 6 h to give 88.4% guaiacol

127:95082
Preparation of 4-methoxyphenol from hydroquinone and methanol at controlled pressure and temperature.
Kawasaki, Hiroshi (Idemitsu Petrochemical Co., Ltd., Japan).  Jpn. Kokai Tokkyo Koho JP 09151151 A2 10 Jun 1997 Heisei, 15 PP. (Japan).  CODEN: JKXXAF.  CLASS: ICM: C07C043-23.  ICS: B01J021-06; B01J021-12; B01J021-14; B01J029-06; C07C041-09; C07B061-00.  APPLICATION: JP 95-313924 1 Dec 1995.  DOCUMENT TYPE: Patent CA Section: 25 (Benzene, Its Derivatives, and Condensed Benzenoid Compounds)
4-MeOC6H4OH (I), useful as a polymn. inhibitor for acrylic compds., a stabilizer for photosensitive materials, etc. (no data), and as a synthetic intermediate, is prepd. in high conversion and selectivity by continuously feeding hydroquinone (II) and MeOH at a liq. phase to a solid acid catalyst layer at 0.5-10.0 MPa and 200-350°.  The reaction is preferably performed at WHSV 0.5-30 h-1 and a MeOH/II mol ratio 3-30.  A MeOH soln. of II was passed through a column packed with a-Al2O3 and N 631 (SiO2-Al2O3) at 248-254°, 4.1 MPa, and WHSV 0.85 for 7 .5 h to give a product contg. 62.7 wt.% I at II conversion 88.4%.

127:81239
Process and etherification catalysts for the production of alkyl ethers of phenols from phenols and alkanols.
Ariyoshi, Kimio; Satoh, Yuuichi; Saito, Noboru (Nippon Shokubai Co., Ltd., Japan).  Eur. Pat. Appl. EP 781751 A1 2 Jul 1997, 16 pp.  DESIGNATED STATES: R:  DE, FR, GB, IT. (European Patent Organization).  CODEN: EPXXDW.  CLASS: ICM: C07C041-09.  ICS: C07C043-20.  APPLICATION: EP 96-309513 27 Dec 1996.  PRIORITY: JP 95-342277 28 Dec 1995.  DOCUMENT TYPE: Patent CA Section: 25 (Benzene, Its Derivatives, and Condensed Benzenoid Compounds) Section cross-reference(s): 45, 67
Alkyl ethers of phenols (e.g., anisole) are prepd. in high yield and selectivity by the etherification of a phenol (e.g., PhOH) with an alkanol (e.g., MeOH) in the presence of an oxide catalyst comprising a supported alkali metal (e.g., Cs) as a constituent element.

130:324980
Convenient method for the ortho-formylation of phenols.
Hofslokken, Nini U.; Skattebol, Lars (Department of Chemistry, University of Oslo, Oslo N-0315, Norway).  Acta Chem. Scand., 53(4), 258-262 (English) 1999 Munksgaard International Publishers Ltd.  CODEN: ACHSE7.  ISSN: 0904-213X.  DOCUMENT TYPE: Journal CA Section: 25 (Benzene, Its Derivatives, and Condensed Benzenoid Compounds)
Phenolic derivs. are formylated selectively ortho to the hydroxy group by paraformaldehyde with magnesium dichloride-triethylamine as base.  With alkyl-substituted phenols, e.g., 2-, 3-, 4-MeC6H4OH, excellent yields of the corresponding salicylaldehyde derivs. were obtained.  Similar results were obtained with 2-, 3-, and 4-chloro-substituted phenols and with 3-and 4-methoxyphenol, while 2-methoxyphenol was unreactive.  A good yield of Me 3-formyl-4-hydroxybenzoate was obtained by this method as well, but generally phenols with electron-attracting groups reacted sluggishly; the long reaction times required caused the formation of byproducts, particularly MOM-derivs. of the phenols.

[Vitus_Verdegast]

10 gr p-MeO-phenol was dissolved in a solution of 13 gr NaOH in 50 ml H₂O with slight heating on the waterbath. The temp of the bath was raised to 60°C and there was added, dropwise, from 2 separate addition funnels, 30 gr chloroform and a sol. of 39 gr NaOH in 40 ml water (note 1) with stirring. At the end of the addition a voluminous yellow precipitate formed. The solution was heated for an hour at 60°C (bath temp.), and allowed to cool. The brown precipitate was filtered off and washed twice with a small volume of methanol (note 2). The precipitate was now dark yellow. This was dissolved in 56 ml H₂O and slightly acidified with dilute HCl. This is extracted with 30 ml toluene and the solvent evaporated. This leaves a darkred oily residue, which was steam distilled (note 3) until the yellowgreen colour of the condensed water disappeared. about 200 ml of destillate were collected. This was saturated with salt, extracted with 50 ml of ether and the ether was evaporated, leaving 3 grams of a yellow oil.  

note 1: SWIM had run out of (pharm. grade) NaOH so he had to add 20 gr of shady drain-opener pellets he bought at 'Achmed's store' once. The package says 'Bilesimi sodyum hidroksit (Na OH)' but the resulting solution clearly had an ammonia smell.  

note 2: According to

Patent GB1377317

note 3: I've messed around with sodium bisulfite before but never got a reasonably pure product and I always seemed to lose quite an amount in the alcohol washings.
Steam distillation is the way to go for purification.

[GC_MS]

This was saturated with salt, extracted with 50 ml of ether and the ether was evaporated, leaving 3 grams of a yellow oil.  

No reason to be mad, yet. In my experience, Reimer-Tiemann formylation is one of these things you have to practise a couple of times before you can yourself a "master". I can't remember my first Reimer-Tiemann reactions to yield something of interest... Tar formation is a major problem, unless you know the tricks.

[Mountain_Girl]

Vitus,

In my last R-T I got 3.17 g 2-OH-5-meo BA from 10 g p-meo phenol (which was not the snow white stuff, more like creamy coffee color - what did yours look like ?). Some stupidity cost me an extra ~1/2 g. So I know about 4 g aldehyde per 10 g phenol is realistic. Also, it may improve your yield if you run closer 70°C (as in the synth on at Rhod's).

I just lovvvve the smell of the aldehyde...like nuts and a new plastic raincoat.

[Antoncho]

Ahem.... I am fairly certain that the yields may bee further improved. Maybee you, guys, aren't so patient w/steam-distillation? It's a SLOW process. SWIM usually added salt to speed it up.

Also - just to bee sure - good care should bee taken to thoroughly saturate the post-distillation mixtr w/NaCl when xtracting.


Actually, why don't you try out this variation

Post 330714

(Antoncho: "A patented improvement", Chemistry Discourse) - i once told it didn't work well, but SWIM used real dirty p-MeO-phenol, i think if you use the white stuff, everything should bee okay.

I also remember reading that RT works actually better in alcoholic alkali - the book said that it "improved the yield, minimized side-rxns and required less time and alkali conc. as well as lower temperature". Alas, i can't remember where i read it, but will try to find the ref...





Antoncho

[Vitus_Verdegast]

I encountered a lot of tar formation before when i let the bath temp climb to 80°C.

I mainly used directions from the GB patent, just tweaked the amount of water a bit when scaling down, and I used a small excess of reactants, because of uncertain quality of the drain opener NaOH.

btw SWIM's p-MeO-phenol had a light brown colour, due to prolonged exposure to air.

There's an interesting article in Tet. Lett., 39, 1979, p.3753-3756:


abstract:
Quaternary ammonium salts were found inactive as phase transfer catalysts in the R-T rxn. Tertiary amines on the other hand, proved to have significant effect on the process.

A minor increase in conversion (5%) was observed however, when the quaternary ammonium salt was also a surface-active agent, eg. hexadecyl trimethyl ammonium bromide.

Since it it known that simple tertiary amines can also catalyse dichlorocarbene reactions, we have added various aliphatic tertiary amines to R-T rxn mixtures. The results are given in the table.

We suggest that while quat. ammonium salts can extract and activate only one substrate, the tertiary amines can simultaneously activate both the phenoxide ion and the dichlorocarbene.

The following sequence of steps is probably involved in the mechanism of the catalytic reaction:

a) Generation of dichlorocarbene in the water-chloroform interphase :

    CHCl₃ --(OH^-)--> :CCl₂ + H₂O + Cl^-

b) Reaction of dichlorocarbene with the tertiary amine 
 followed by another chloroform molecule and generation of additional dichlorocarbene :

    :CCl₂ + R₃N -->  R₃N^{+ -}CCl₂  --( CHCl₃)-->  (R₃N⁺ CHCl₂) ^-CCl₃ --->  (R₃N⁺ CHCl₂) ^-Cl + :CCl₂


c) Anion exchange of the quaternary chloride salt with phenoxide :

    (R₃N⁺ CHCl₂) ^-Cl  --(^-OPh)-->  (R₃N⁺ CHCl₂) ^-OPh


d) Intramolecular rearrangement of the phenoxide salt to yield mainly ortho alkylated phenol and the original tertiary amine. This proposed step is similar in nature to the well-known Sommelet rearrangement :

     (R₃N⁺ CHCl₂) ^-OPh   --->  OHPhCHCl₂ + R₃N


e) The dichloro product is eventually hydrolysed to yield salicylaldehyde


Table

catalyst - salicylaldehyde (%) - 4-hydroxybenzaldehyde (%)


none  -  26.0  -  4.1

(n-C₄H₉)₃N  -  64.5  -  5.8

(n-C₆H₁₃)₃N  -  53.4  -  5.2

(n-C₈H₁₇)₃N  -  49.0  -  3.9



Reaction conditions :

0.05 mol phenol, 0.3 mol chloroform, 0.001 mol catalyst, 50 ml benzene, 0.3 mol NaOH 50% sol. in water. Magnetic stirring at 60° for 25 min. Hydrolysis with 50 ml 10% HCl.

[Vitus_Verdegast]

TITLE The Reimer-Tiemann Reaction, Enhanced by Ultrasound
AUTHORS Cochran, John C.; Melville, Margaret G.
SOURCE Synth.Commun. 1990, 20: 4 609-616
ABSTRACT Significant improvement in yields for Reimer-Tiemann reactions are obtained when the reaction is carried out in the presence of ultrasound.
Full Text:

TITLE THE REIMER-TIEMANN REACTION IN SLIGHTLY HYDRATED SOLID-LIQUID MEDIUM: A NEW METHOD FOR THE SYNTHESIS OF FORMYL AND DIFORMYL PHENOLS
AUTHORS Thoer, A.; Denis, G.; Delmas, M.; Gaset, A.
SOURCE Synth.Commun. 1988, 18: 16-17 2095-2102
DOCUMENT TYPE Journal
CODEN SYNCAV
LANGUAGE EN
CNR 5738003
ABSTRACT Formylation of phenol in weakly hydrated heterogeneous solid-liquid medium makes it possible to transform phenol into salicylaldehyde and parahydroxybenzaldehyde with a ratio of 4.5/1 with excellent yield.Use of methanol as cosolvent modifies the orientation of this reaction, which leads for the first time to simultaneous synthesis of salicylaldehyde and
parahydroxybenzaldehyde, of 2-hydroxy 1,3-benzenedicarboxaldehyde, and of 2-hydroxy 1,3-
benzenedicarboxaldehyde. Experimental conditions make it possible to easily extract each of these molecules.



TITLE Photoformylation of Phenols
AUTHORS Fahmy, A. M.; Mahgoub, S. A.; Aly, M. M.; Badr, M. Z. A.
SOURCE Indian J.Chem.Sect.B 1984, 23: 5 474-475
DOCUMENT TYPE Journal
CODEN IJSBDB
LANGUAGE EN
CNR 5574527
ABSTRACT Photoformylation of phenol, o-, p- and m-cresols, p-chlorophenol, p-bromophenol, p-nitrophenol and p-hydroxydiphenyl with chloroform in the presence of aq.KOH or pyridine affords the corresponding aldehydes; formyl group entering the position ortho to OH function.A
plausible mechanism, different from that of well known Reimer-Tiemann, has been suggested.



TITLE Reimer-Tiemann reactions of guaiacol and catechol in the presence of â-cyclodextrin
AUTHORS Divakar, S.; Maheswaran, M. M.; Narayan, M. S.
SOURCE Indian J.Chem.Sect.B 1992, 31: 8 543-546
DOCUMENT TYPE Journal
CODEN IJSBDB
LANGUAGE EN
CNR 5751452
ABSTRACT Fairly high selectivities with respect to para-product are achieved when guaiacol and catechol are subjected to Reimer-Tiemann reaction in the presence of â-cyclodextrin (BCD).
Although the presence of BCD does not enhance the total aldehyde production, it reduces the proportion of other isomeric aldehydes formed in favour of the para-product.Thus the reaction in the presence of BCD yields 32% more vanillin in the case of guaiacol and 25% more
protocatechuic aldehyde in the case of catechol in comparison to the one in the absence of BCD.

[Vitus_Verdegast]

An attempt was made to methylate a solution of 3 gr of 2-OH-5-MeO-benzaldehyde, 23 gr Na₂CO₃ and 0.1 gr hexadecyltrimethylammonium bromide in 86 ml water with dropwise addition of 10 ml MeHSO₄, keeping the temp. at reflux and letting it boil for an additional 4 hours. After standard work-up no methylated product was obtained.

I've seen 2 refs detailing the methylation of a hydroxyl-group ortho- to a nitro-group using MeI in DMSO claiming 91% yield. I'll dig those up tomorrow.

[Antoncho]

Get them, Vitus! This is exactly what we need!


Antoncho