397:
278:
422:
356:
48:
335:
and the Lewis basic ether. This Lewis adduct can reversibly dissociate to give a dibromoboryl oxonium cation and Br. Rupture of the ether linkage occurs through the subsequent nucleophilic attack on the oxonium species by Br to yield an aryloxydibromoborane and methyl bromide. Upon completion of
327:, which can be used at room temperature or below, is a more specialized reagent for the demethylation of aryl methyl ethers. The mechanism of ether dealkylation proceeds via the initial reversible formation of a
167:. Much interest has been shown in converting this abundant form of biomass into useful chemicals (aside from fuel). One step in such processing is demethylation. The demethylation of
1319:
Yamaguchi, Seiji; Nedachi, Masahiro; Yokoyama, Hajime; Hirai, Yoshiro (October 1999). "Regioselective demethylation of 2,6-dimethoxybenzaldehydes with magnesium iodide etherate".
30:) from a molecule. A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen atoms.
1146:
284:
Another classical (but, again, harsh) method for the removal of the methyl group of an aryl methyl ether is to heat the ether in a solution of
396:
171:, a derivative of lignin, requires 250 °C (482 °F) and strong base. Pulp and paper industry]] digests lignin using aqueous
117:
699:
591:
560:
296:. The cleavage of ethers by hydrobromic or hydroiodic acid proceeds by protonation of the ether, followed by displacement by
1197:
Zuo, Li; Yao, Shanyan; Wang, Wei; Duan, Wenhu (June 2008). "An efficient method for demethylation of aryl methyl ethers".
1276:
1173:
374:) also cleave aryl ethers, sometimes under mild conditions. Other strong nucleophiles that have been employed include
1122:
1049:
120:
are also active for demethylation of DNA, operating by a similar stoichiometry. These reactions, which proceed via
175:, which partially depolymerizes the lignin. Delignification is accompanied by extensive O-demethylation, yielding
993:
608:"Crystal Structure of Dicamba Monooxygenase: A Rieske Nonheme Oxygenase that Catalyzes Oxidative Demethylation"
274:-methylpyridinium chloride, either directly or by subsequent methyl transfer from methyl chloride to pyridine.
210:(melting point 144 °C (291 °F)) at 180 to 220 °C (356 to 428 °F), sometimes with excess
581:
223:
1405:
237:< 10) that accounts for the harsh conditions required, given the much weaker acidity of pyridinium (
476:
derivatives. A modern variation of the von Braun reaction was developed, where BrCN was superseded by
432:, KOH, and alcohol was heated in an autoclave. Although the product of this reaction was the expected
1346:
Merlic, Craig A.; Aldrich, Courtney C.; Albaneze-Walker, Jennifer; Saghatelian, Alan (1 April 2000).
1348:"Carbene Complexes in the Synthesis of Complex Natural Products: Total Synthesis of the Calphostins"
1400:
125:
552:
413:
854:
52:
866:
821:
Schmidt, Sandy (2022). "Expanding the repertoire of Rieske oxygenases for O-demethylations".
524:
328:
728:
991:
Lawson, J. A.; DeGraw, J. I. (1977). "An improved method for O-demethylation of codeine".
849:
8:
1199:
477:
732:
367:
1372:
1347:
1140:
798:
773:
749:
716:
632:
607:
545:
459:
1332:
270:
or chloride ion (depending on the substrate) to give the free phenol and, ultimately,
1377:
1272:
1232:
1179:
1169:
1128:
1118:
1095:
1055:
1045:
1018:
1010:
946:
894:
870:
803:
754:
695:
672:
637:
587:
556:
305:
211:
206:-methylmorphine), have been demethylated by heating the substance in molten pyridine
964:
Weissman, Steven A.; Zewge, Daniel (2005). "Recent
Advances in Ether Dealkylation".
655:
Pedersen MT, Helin K (Nov 2010). "Histone demethylases in development and disease".
1367:
1359:
1328:
1301:
1264:
1208:
1087:
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1002:
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942:
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627:
619:
389:
etherate. An example of this being used is in the synthesis of the natural product
386:
382:
381:
Aromatic methyl ethers, particularly those with an adjacent carbonyl group, can be
324:
285:
408:
Methyl esters also are susceptible to demethylation, which is usually achieved by
304:. A slightly milder set of conditions uses cyclohexyl iodide (CyI, 10.0 equiv) in
1212:
834:
789:
289:
113:
1268:
1227:
889:
409:
172:
977:
668:
623:
1394:
1305:
1165:
1132:
1099:
1059:
1014:
692:
The
Ubiquitous Roles of Cytochrome P450 Proteins: Metal Ions in Life Sciences
441:
207:
121:
1183:
1381:
950:
874:
807:
758:
676:
641:
606:
Dumitru, Razvan; Jiang, Wen Zhi; Weeks, Donald P.; Wilson, Mark A. (2009).
520:
363:
259:
219:
176:
144:
133:
51:
Dicamba, a widely used herbicide, biodegrades by demethylation to give 3,6-
23:
1022:
577:
516:
504:
293:
229:
formed. The mechanism of this reaction starts with proton transfer from
148:
129:
77:
56:
34:
1363:
1160:
Streitwieser, Andrew; Heathcock, Clayton H.; Kosower, Edward M. (1992).
1091:
1006:
740:
218:. Quantitative analysis for aromatic methyl ethers can be performed by
1345:
1292:
Mirrington, R. N.; Feutrill, G. I. (1973). "Orcinol
Monomethyl Ether".
500:
390:
345:
248:
230:
180:
69:
689:
436:, a highly reactive dimerization product in the mother liquors called
277:
485:
198:
Historically, aryl methyl ethers, including natural products such as
355:
1041:
429:
421:
375:
267:
168:
73:
489:
467:
349:
317:
297:
199:
152:
85:
81:
583:
Advanced
Organic Chemistry: Reactions, Mechanisms, and Structure
488:
is an application of this reaction, as well as the synthesis of
47:
1258:
437:
412:. Highly specialized demethylations are abundant, such as the
301:
192:
164:
140:
59:
336:
the reaction, the phenol is liberated along with boric acid (H
1318:
772:
Pietzke, Matthias; Meiser, Johannes; Vazquez, Alexei (2020).
575:
481:
16:
Process of removing one or more methyl groups from a molecule
1159:
847:
1225:
1076:
Burwell, Robert L. (1954-08-01). "The
Cleavage of Ethers".
542:
472:
463:
433:
266:
of the arylmethyloxonium ion at the methyl group by either
543:
Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. (2001).
238:
233:
ion to the aryl methyl ether, a highly unfavorable step (
717:"TET enzymes, TDG and the dynamics of DNA demethylation"
605:
22:
is the chemical process resulting in the removal of a
88:, in lysine derivatives, and in some forms of DNA.
771:
690:Roland Sigel; Sigel, Astrid; Sigel, Helmut (2007).
1291:
544:
1392:
931:Journal of the Air Pollution Control Association
683:
1115:Organic chemistry : structure and function
1112:
348:of the dibromoborane derivative during aqueous
163:Methoxy groups heavily decorate the biopolymer
1196:
887:
848:W. Boerjan; J. Ralph; M. Baucher (June 2003).
586:(6th ed.), New York: Wiley-Interscience,
315:to generate a small amount of hydrogen iodide
251:aryl methyl ether (an arylmethyloxonium ion, p
1113:Vollhardt, Peter; Schore, Neil (2014-01-01).
1035:
963:
654:
990:
400:Synthesis of Calphostin A by regioselective
354:
331:adduct between the strongly Lewis acidic BBr
276:
258:= –6.7 for aryl = Ph). This is followed by
112:One family of such oxidative enzymes is the
708:
1259:Robert E. Ireland; David M. Walba (1977).
1164:(4th ed.). Upper Saddle River, N.J.:
1145:: CS1 maint: location missing publisher (
774:"Formate Metabolism in Health and Disease"
714:
191:Demethylation often refers to cleavage of
118:Alpha-ketoglutarate-dependent hydroxylases
1371:
1038:Organic syntheses based on name reactions
797:
748:
631:
536:
1352:Journal of the American Chemical Society
867:10.1146/annurev.arplant.54.031902.134938
46:
1075:
820:
569:
186:
1393:
1219:
920:
841:
458:-demethylation of 3° amines is by the
344:) and hydrobromic acid (aq. HBr) upon
1071:
1069:
158:
1226:J. F. W. McOmie, D. E. West (1969).
1036:Hassner, Alfred; Stumer, C. (2002).
33:The counterpart of demethylation is
13:
1117:(Seventh ed.). New York, NY.
1066:
715:Kohli RM, Zhang Y (October 2013).
648:
447:
395:
40:
14:
1417:
1162:Introduction to organic chemistry
143:are steps in the biosynthesis of
420:
124:, exploit the slightly weakened
84:N-methyl groups, which occur in
1339:
1312:
1285:
1252:
1190:
1153:
1106:
1029:
984:
957:
914:
881:
994:Journal of Medicinal Chemistry
943:10.1080/00022470.1962.10468107
814:
765:
599:
1:
1333:10.1016/S0040-4039(99)01411-2
530:
151:. Methyl groups are lost as
68:Demethylation is relevant to
1263:. Vol. 56. p. 44.
1213:10.1016/j.tetlet.2008.04.070
921:Hansen, G. A. (1962). "Odor
835:10.1016/j.checat.2022.07.005
790:10.1016/j.molmet.2019.05.012
612:Journal of Molecular Biology
214:, in a process known as the
7:
1269:10.1002/0471264180.os056.11
1040:(2nd ed.). Amsterdam:
510:
72:. Demethylation of DNA is
10:
1422:
1247:, vol. 5, p. 412
909:, vol. 3, p. 745
470:to give the corresponding
227:-methylpyridinium chloride
216:Zeisel–Prey ether cleavage
195:, especially aryl ethers.
978:10.1016/j.tet.2005.05.041
669:10.1016/j.tcb.2010.08.011
624:10.1016/j.jmb.2009.07.021
1306:10.15227/orgsyn.053.0090
1228:"3,3'-Dihydroxybiphenyl"
888:Irwin A. Pearl (1949).
553:Oxford University Press
551:. Oxford, Oxfordshire:
440:was also discovered by
414:Krapcho decarboxylation
247:= 5.2) compared to the
890:"Protocatechulic Acid"
855:Annu. Rev. Plant Biol.
657:Trends in Cell Biology
405:
359:
281:
179:, which is emitted by
139:Demethylation of some
63:
53:dichlorosalicylic acid
850:"Lignin biosynthesis"
480:. The preparation of
399:
358:
280:
222:determination of the
50:
927:in a Kraft Pulp Mill
778:Molecular Metabolism
519:, the addition of a
292:sometimes also with
187:In organic chemistry
1321:Tetrahedron Letters
1200:Tetrahedron Letters
1092:10.1021/cr60170a003
1007:10.1021/jm00211a037
741:10.1038/nature12750
733:2013Natur.502..472K
694:. New York: Wiley.
576:Smith, Michael B.;
478:ethyl chloroformate
385:demethylated using
499:-demethylation of
460:von Braun reaction
406:
368:diorganophosphides
360:
313:-dimethylformamide
282:
159:Biomass processing
64:
1406:Organic reactions
1364:10.1021/ja994313+
1358:(13): 3224–3225.
1327:(41): 7363–7365.
1294:Organic Syntheses
1261:Organic Syntheses
1245:Collected Volumes
1233:Organic Syntheses
1207:(25): 4054–4056.
972:(33): 7833–7863.
907:Collected Volumes
895:Organic Syntheses
701:978-0-470-01672-5
593:978-0-471-72091-1
562:978-0-19-850346-0
547:Organic Chemistry
393:, as seen below.
212:hydrogen chloride
80:. These enzymes
55:, catalyzed by a
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1079:Chemical Reviews
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387:magnesium iodide
383:regioselectively
325:Boron tribromide
286:hydrogen bromide
1421:
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1401:Gene expression
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329:Lewis acid-base
290:hydrogen iodide
263:
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114:cytochrome P450
107:
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43:
41:In biochemistry
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1175:978-0139738500
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1086:(4): 615–685.
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1001:(1): 165–166.
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937:(9): 409–436.
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861:(1): 519–549.
840:
823:Chem Catalysis
813:
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682:
663:(11): 662–71.
647:
618:(2): 498–510.
598:
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561:
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529:
528:
527:
512:
509:
452:
451:-demethylation
446:
426:
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410:saponification
404:-demethylation
376:thiolate salts
371:
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173:sodium sulfide
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469:
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462:, which uses
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450:
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442:Charles Dodds
439:
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428:A mixture of
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134:methyl ethers
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122:hydroxylation
119:
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83:
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61:
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44:
38:
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31:
25:
21:
20:Demethylation
1355:
1351:
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582:
578:March, Jerry
571:
546:
538:
521:methyl group
496:
494:
471:
455:
454:
448:
427:
407:
401:
391:Calphostin A
380:
378:like EtSNa.
364:nucleophiles
361:
323:
316:
310:
306:
283:
271:
252:
240:
234:
224:
215:
203:
197:
190:
177:methanethiol
162:
145:testosterone
138:
130:methylamines
111:
100:+ O → R
78:demethylases
67:
32:
24:methyl group
19:
18:
966:Tetrahedron
517:Methylation
505:desipramine
490:GSK-372,475
294:acetic acid
181:paper mills
149:cholesterol
104:N-H + CH
70:epigenetics
57:dioxygenase
35:methylation
1395:Categories
531:References
501:imipramine
346:hydrolysis
249:protonated
231:pyridinium
1141:cite book
1133:866584251
1100:0009-2665
1060:190810761
1015:0022-2623
784:: 23–37.
525:substrate
486:arecoline
362:Stronger
126:C-H bonds
74:catalyzed
1382:23335811
1184:52836313
1042:Pergamon
951:13904415
875:14503002
808:31402327
759:24153300
677:20863703
642:19616011
580:(2007),
511:See also
430:anethole
366:such as
268:pyridine
264:2 attack
169:vanillin
86:histones
1373:3548573
799:7056922
750:4046508
729:Bibcode
633:3109874
468:reagent
466:as the
318:in situ
298:bromide
200:codeine
153:formate
141:sterols
82:oxidize
1380:
1370:
1300:: 90.
1275:
1182:
1172:
1131:
1121:
1098:
1058:
1048:
1023:833817
1021:
1013:
949:
873:
806:
796:
757:
747:
721:Nature
698:
675:
640:
630:
590:
559:
503:gives
438:dianol
370:(LiPPh
350:workup
302:iodide
193:ethers
165:lignin
60:enzyme
523:to a
484:from
482:Paxil
1378:PMID
1273:ISBN
1240:: 13
1180:OCLC
1170:ISBN
1147:link
1129:OCLC
1119:ISBN
1096:ISSN
1056:OCLC
1046:ISBN
1019:PMID
1011:ISSN
947:PMID
902:: 85
871:PMID
804:PMID
755:PMID
696:ISBN
673:PMID
638:PMID
588:ISBN
557:ISBN
495:The
473:nor-
464:BrCN
434:anol
321:.
147:and
132:and
96:N-CH
1368:PMC
1360:doi
1356:122
1329:doi
1302:doi
1265:doi
1209:doi
1088:doi
1003:doi
974:doi
939:doi
929:".
923:and
863:doi
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