Click Chemistry: Diverse Chemical Function from a Few Good Reactions
Angewandte Chemie International Edition, 2001 · paper · Chemistry
Describes "click chemistry," an approach to quickly making useful compounds and libraries through carbon–heteroatom links, inspired by nature's preference for such bonds. It sets out the criteria a reaction must meet and gives examples of molecular frameworks made this way.
3 findings
Substance Scheme 5 gives 1 mol of chloramine-T as "TsNNaCl·3H2O (263 g, 1 mol)" in the sodium cinnamate example and as "TsNNaCl (283 g, 1 mol)" in the disodium fumarate example; the first two examples give "TsNNaCl·3H2O (35.2 g, 125 mmol)", i.e. 281.6 g/mol, which agrees with 283 g and not with 263 g.
- p. 9 Scheme 5, third reaction (sodium cinnamate), reagent line
TsNNaCl·3H2O (263 g, 1 mol)
- p. 9 Scheme 5, fourth reaction (disodium fumarate), reagent line
TsNNaCl (283 g, 1 mol)
- p. 9 Scheme 5, first example
TsNNaCl·3H2O (35.2 g, 125 mmol)
- p. 9 Scheme 5, third example (sodium cinnamate)
TsNNaCl·3H2O (263 g, 1 mol), H2O
Only the authors can say what is right here.
Judge's note: Read on a 5x render of Scheme 5 (PDF p. 9; the scheme is an embedded low-resolution image). Row 3 reads 263 and row 4 reads 283; the middle digits differ visibly, though a 6/8 confusion in so blurred an image cannot be wholly excluded. The check is internal to the scheme: 35.2 g for 125 mmol fixes the molar mass used at 281.6 g/mol, so 263 g would be 0.93 mol. Probably a digit error for 283 g, but only the authors can say which figure was used.
Second check: another model agreed
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Reference or label Scheme 13 caption: "Generation and reactions of activated sulfonium (thiiranium) electrophile 14." In the scheme and text 14 is the neutral dichloride and the episulfonium ion is 15 ("provides episulfonium intermediates such as 15"; "the chloride in 14").
- p. 12 Scheme 13 caption
Generation and reactions of activated sulfonium (thiiranium) electrophile 14.
- p. 12 Section 3.1, text on mustard-type compounds
which provides episulfonium intermediates such as
- p. 12 Section 3.1, left column
which provides episulfonium intermediates such as 15
- p. 12 Section 3.1, left column
(for example, the chloride in 14)
Only the authors can say what is right here.
Judge's note: Scheme 13 on PDF p. 12: 14 is drawn as the neutral dichloro sulfide from cyclooctadiene and SCl2 (210 g, m.p. 101-102 °C); 15 is the charged three-membered sulfonium species with Cl− counterion. The text on the same page uses the numbers the same way. The caption attaches "sulfonium (thiiranium)" to 14. The caption could loosely mean the precursor 14 that reacts by way of the thiiranium ion, so the authors should say whether 15 or a reworded caption was intended.
Second check: another model agreed
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Wording Text: cyclic hydrazide 21 "undergoes condensation with aromatic aldehydes to give azomethine ylides 22"; Scheme 15 draws 22 as an N–N dipole (ArCH=N+–N−) and its caption calls it the "hydrazine-derived [2+3] dipole 22", which is an azomethine imine rather than an azomethine ylide.
- p. 13 Section 3.2, text describing Scheme 15
to give azomethine ylides 22
- p. 13 Scheme 15 caption
hydrazine-derived [2+3] dipole 22
- p. 8 Section 2.3 end
for [3+2] cycloaddition with alkynes
- p. 9 Section 3
Huisgens [2+3] cycloaddition
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the nomenclature convention that a C=N+–C− dipole is an azomethine ylide and a C=N+–N− dipole is an azomethine imine. Scheme 15 and the text read on PDF p. 13: 22 is drawn with the aldehyde carbon on one ring nitrogen of the N–N unit, and the caption says hydrazine-derived. The [2+3]/[3+2] notation point also raised in this cluster is the same as C006 and is not repeated here.
Second check: another model agreed
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19 minor (typos and the like; most checked by the judge only)
Reference or label Scheme 5, disodium fumarate example: reagent is labelled "TsNNaCl (283 g, 1 mol)" without "·3H2O", although 283 g per mole is the mass the same scheme uses for the trihydrate ("TsNNaCl·3H2O (35.2 g, 125 mmol)", 281.6 g/mol).
- p. 9 Scheme 5, fourth reaction (disodium fumarate), reagent line
TsNNaCl (283 g, 1 mol)
Judge's note: Read on a 5x render of Scheme 5 (PDF p. 9). The other three aminohydroxylation rows write the trihydrate explicitly; row 4 omits it while giving the trihydrate's mass per mole as fixed by rows 1-2 of the same scheme. A label omission; distinct from the 263 g figure in C007.
Second check: another model agreed
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Wording Text says the special olefins react "with only one equivalent of the haloamine salt" and cites Scheme 5, where the first two aminohydroxylations use "TsNNaCl·3H2O (35.2 g, 125 mmol)" for 100 mmol of substrate (1.25 equiv); the third and fourth use 1 mol per 1 mol.
- p. 8 Section 2.5, second paragraph
with only one equivalent of the haloamine salt
- p. 9 Scheme 5, first and second reactions
TsNNaCl·3H2O (35.2 g, 125 mmol)
Judge's note: Text on PDF p. 8 (Section 2.5); Scheme 5 read on a zoomed render of PDF p. 9: rows 1 and 2 give 125 mmol chloramine-T against 17.5 g/100 mmol and 20.5 g/100 mmol substrate. No statement elsewhere qualifies "one equivalent". Loose wording rather than a wrong number.
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Wording Scheme 5, dihydroxylation of sodium cinnamate (170 g, 1 mol): product "200 g (99%)"; for the sodium dihydroxyphenylpropanoate drawn (C9H9NaO4) 200 g from 1 mol is about 98%.
- p. 9 Scheme 5, last example
200 g (99%)
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the molar mass of the drawn product, about 204.2 g/mol from its formula C9H9NaO4 (not printed in the paper). Scheme read on PDF p. 9. 200/204.2 = 97.9%; 99% would be about 202 g. A one-point difference that a rounded mass or the isolated form of the product could explain.
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Wording Scheme 10 labels the product ">95 : 5 Regioselectivity" while its own yields box lists the 3-ethynylaniline entry as "82% (94:6 mixture of regioisomers)".
- p. 11 Scheme 10, under the product structure
>95 : 5 Regioselectivity
- p. 11 Scheme 10, yields box, 3-ethynylaniline entry
82% (94:6 mixture of regioisomers)
Judge's note: Both labels read on the page image of PDF p. 11 (small embedded image, legible). 94:6 lies below >95:5 and the scheme does not say the general label excludes that amine. The 94:6 entry is flagged in the scheme itself, so a reader is not misled; minor internal inconsistency.
Second check: another model agreed
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Wording Scheme 18 caption reads "A click chemistry library sequence from olefinic acids." but the starting material drawn is an α,β-unsaturated amide (R1CH=CH-C(O)NR2R3) and the text says "aminohydroxylation of α,β-unsaturated amides is also an attractive starting point".
- p. 14 Scheme 18 caption
A click chemistry library sequence from olefinic acids.
- p. 14 Section 4, paragraph introducing Scheme 18
unsaturated amides is also an attractive starting point
- p. 14 Section 4, left column
unsaturated amides is also an attractive starting point for the
- p. 14 Main text before Scheme 18
aminohydroxylation of α,β-unsaturated amides
Judge's note: Viewed page 14. The scheme's first structure carries C(O)NR2R3 and the products 31a/31b, 32 and 33 keep the amide; the running text names α,β-unsaturated amides. The caption says olefinic acids. Amides are acid derivatives, so the caption may be loose shorthand; either form could be intended, hence a minor consistency point.
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Typo Introduction: "due in effect to the loss of one “equivalent” of ester, resonance stabilization, the first" has a stray comma after "ester"; the phrase intended is "ester resonance stabilization".
- p. 2 Section 1, last lines of the left column
of one “equivalent” of ester, resonance stabilization, the first
Judge's note: Read on the page image (PDF p. 2, last lines of right column). The comma is printed and splits the noun phrase. Cosmetic.
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Typo The dipolar cycloaddition is written "[3+2]" (p. 2011 "for [3+2] cycloaddition with alkynes"; p. 2016 "to give [3+2] cycloadducts") and "[2+3]" (p. 2012 "Huisgen's [2+3] cycloaddition"; p. 2015 "other types of [2+3] reactions"; Scheme 15 caption "hydrazine-derived [2+3] dipole 22").
- p. 8 Section 2.3, last paragraph
[3+2]
- p. 9 Section 3, first paragraph
[2+3] cycloaddition
- p. 13 Scheme 15 caption
[2+3]
- p. 13 Section 3.2, text after Scheme 15
[3+2] cycloadducts
Judge's note: All five occurrences read on the page images (the text layer drops the plus sign). On PDF p. 13 the Scheme 15 caption and the sentence describing it use opposite orders. Both forms are in use and the meaning is the same; notation inconsistency only.
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Typo Section 4: "1,3-dipolar addition of the bis-azide with diethylacetylene dicarboxylate"; the name is mis-spaced for diethyl acetylenedicarboxylate (the diester of acetylenedicarboxylic acid).
- p. 13 Section 4, first paragraph
diethylacetylene dicarboxylate
- p. 13 Section 4, first paragraph
with diethylacetylene dicarboxylate
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the standard name of EtO2C–C≡C–CO2Et is diethyl acetylenedicarboxylate, and "diethylacetylene" would denote a different unit. The printed wording was read on PDF p. 13 (line break after "diethylacetylene" has no hyphen). The compound meant is clear from context; cosmetic.
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Typo "The resulting primary 2-amino group of compounds 34 have been capped with more than sixty electrophiles to date": singular subject "group" with plural verb "have".
- p. 14 Section 4, last paragraph
primary 2-amino group of compounds 34 have
- p. 14 Section 4, right column
The resulting primary 2-amino group of compounds 34 have
- p. 14 Section 4, last paragraph
The resulting primary 2-amino group of compounds 34 have been capped with more than sixty electrophiles
Judge's note: Viewed page 14, right column below Scheme 18; the sentence is printed as quoted. Grammatical agreement error ("group ... has" or "groups ... have").
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Typo Note [12]: "The Dieckman condensation has enormous scope": the reaction name is printed with a single n (usual spelling "Dieckmann").
- p. 15 Reference/note [12]
The Dieckman condensa-
- p. 15 reference [12]
The Dieckman condensa-tion has enormous scope
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: that the named reaction is spelled Dieckmann (after Walter Dieckmann). Viewed page 15; "Dieckman condensa-tion" is printed with one n in note [12]. The name appears nowhere else in the article for comparison.
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Typo Ref. [38b]: "G. Schlingoff, K. B. Sharpless in Asymmetric Oxidations Reactions: A Practical Approach": author surname possibly misspelled (reviewer says "Schlingloff").
- p. 16 Reference [38b]
G. Schlingoff, K. B. Sharpless
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: that the co-author's name is G. Schlingloff. Viewed page 16; the page prints "G. Schlingoff". The name does not occur elsewhere in the article, so the spelling cannot be checked from the files.
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Typo Ref. [19]: "[19] G. Wilke, A. Eckerle, Appl. Homogeneous Catal. Organomet. Compd. 1996, 1, 358–373; b) P. W. Jolly, G. Wilke ...; c) G. W. Parshall": the first item has no "a)" label although b) and c) follow.
- p. 16 Reference [19]
[19] G. Wilke, A. Eckerle, Appl. Homogeneous Catal. Organomet. Compd.
- p. 16 reference [19]
[19] G. Wilke, A. Eckerle, Appl. Homogeneous Catal. Organomet. Compd. 1996, 1, 358 – 373; b) P. W. Jolly
- p. 16 reference [19]
G. Wilke, A. Eckerle, Appl. Homogeneous Catal. Organomet. Compd. 1996, 1, 358 ± 373; b) P. W. Jolly
Judge's note: Viewed page 16. The entry begins directly with "G. Wilke" after the number, then continues with b) and c). Other multi-part entries on the page (e.g. [22], [24], [32]) begin with a). Not an extraction loss; the label is absent in the image.
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Typo Ref. [38b]: book title printed as "Asymmetric Oxidations Reactions: A Practical Approach" (stray plural "Oxidations").
- p. 16 reference [38b]
Asymmetric Oxidations Reactions: A Practical Approach
Judge's note: Viewed page 16; the title is printed as quoted across a line break. "Oxidations Reactions" is ungrammatical on its face. The exact published title of the book is outside the files, but the stray s is evident.
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Typo Ref. [48]: "Z. Li, K. B. Conser, E. N. Jacobson, J. Am. Chem. Soc. 1993, 115, 5326–5327" while ref. [36b] prints "E. N. Jacobsen": two spellings of what appears to be one author.
- p. 17 Reference [48]
Li, K. B. Conser, E. N. Jacobson
- p. 16 Reference [36b]
E. N. Jacobsen
- p. 17 Reference [48]
Li, K. B. Conser, E. N. Jacobson, J. Am. Chem. Soc. 1993, 115, 5326
- p. 16 Reference [36] b)
E. N. Jacobsen, in
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: that the E. N. Jacobson of ref. [48] is the same person as the E. N. Jacobsen of ref. [36b], and that Jacobsen is the right spelling. Viewed pages 16 and 17; both spellings are printed as quoted. Same initials and same field (asymmetric epoxidation/aziridination) make one person very likely, but the files cannot establish it.
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Typo Ref. [49d]: "Tetrahedron: Assymmetry 1994, 5, 1727–1744": journal name misspelled; printed "Tetrahedron: Asymmetry" in [39], [49g] and [50d].
- p. 17 Reference [49d]
Assymmetry 1994, 5, 1727
- p. 17 Reference [49] g)
Asymmetry 1996, 7, 779
- p. 17 reference [49d]
Tetrahedron: Assymmetry 1994, 5, 1727
- p. 17 reference [49g]
Tetrahedron: Asymmetry 1996, 7, 779
Judge's note: Viewed pages 16 and 17. "Assymmetry" with double s is visible in [49d]; the same journal is spelled "Asymmetry" in [49g] and [50d] on the same page and in [39] on page 16.
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Typo Ref. [48]: "R. E. Rowenthal, S. Masamune, Tetrahedron Lett. 1991, 32, 7373–7376": first author's surname possibly misprinted.
- p. 17 Reference [48]
Rowenthal, S. Masamune, Tetrahedron Lett. 1991, 32, 7373
- p. 17 reference [48]
R. E. Rowenthal, S. Masamune
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the true surname of Masamune's co-author on Tetrahedron Lett. 1991, 32, 7373. Viewed page 17; "Rowenthal" is printed. The reviewers disagree on the correct form (Lowenthal versus Rosenthal), which shows that memory is unreliable here; the name occurs nowhere else in the article. Only a check of the cited paper settles it.
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Typo Ref. [57]: "Opening of aziridines with thiols, see:a) G. Meguerian": missing space after the colon.
- p. 17 Reference [57]
see:a) G. Meguerian
- p. 17 reference [57]
Opening of aziridines with thiols, see:a) G. Meguerian
Judge's note: Viewed page 17; "see:a)" is set without a space in [57], whereas other entries (e.g. [47], [55], [59]) print "see: a)". Present in the image and the text layer.
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Typo Note [43]: "(depending on whether or not a protic or aprotic environment is desired (see refs. [44b] and [45]); in the former case, the addition of water after cooling often results in precipitation of the product.": two opening parentheses, one closing.
- p. 17 Reference/note [43]
(depending on
- p. 17 reference [43]
(depending on whether or not a protic or aprotic environment is desired (see refs. [44b] and [45]); in the former case
Judge's note: Viewed page 17 and the text of note [43] through to its end. The parenthesis opened before "depending" is never closed: only one ")" appears, after "[45]", and the note ends with "product." without a closing parenthesis.
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Typo Ref. [67e]: "F. Lautenschlaeger, Chemistry in Sulfides Conference (Ed.: A. V. Tobolsky), Interscience, New York, 1968, pp. 73–81": the italicised title reads oddly and may be garbled.
- p. 18
Chemistry in Sulfides Conference (Ed.: A. V. Tobolsky)
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the actual title of the Tobolsky-edited 1968 Interscience volume (reviewer suggests "The Chemistry of Sulfides"). Viewed page 18; the entry is printed as quoted, with "Chemistry in Sulfides Conference" in italics. The wording is awkward, but the true title cannot be checked from the files.
Second check: none (judge only)