the 
 field of small - molecule organocatalysis via noncovalent interactions 
 has seen rampant growth over the past decade . this area , which aims to mimic the mechanisms used by nature in 
 enzyme catalysis , is attractive due to its potential for high catalyst 
 tunability and substrate specificity , as well as obviating the use 
 of metals . while such research has resulted in many catalysts operating 
 through bifunctional mechanisms , the primary 
 interaction responsible for electrophile activation occurs through 
 hydrogen - bonding to an acceptor moiety . the consequent lumo - lowering 
 results in rate enhancement . in comparison to metal - based systems 
 ( i.e. , lewis acids ) , current metrics to estimate the reactivity of hydrogen 
 bonding catalysts are ineffective . although pka values of the donor and acceptor may be used to infer 
 hydrogen - bond strengths , this analysis 
 fails to account for several important secondary interactions , including 
 sterics , dual - activation , and binding geometry . as a result , the discovery of reactions compatible with 
 hydrogen - bond catalysis is far outpacing understanding of catalyst 
 interaction and mechanism . indeed , while certain privileged organocatalyst 
 motifs have been identified to be successful for several reaction 
 types , rational design of these structures remains limited , relying 
 on trial and error to achieve optimal reactivity and selectivity . in a previous communication , we described 
 preliminary results showing the utility of small organic chromophore s for the detection of hydrogen - bonding interactions by uv herein , we assess the general utility of this colorimetric 
 sensor as a predictive gauge for the relative reactivity of a broad 
 range of organocatalysts , including several widely used motifs , with 
 the goal of encompassing many different hydrogen - bonding arrays . an 
 additional goal was to validate the sensor measurements across significantly 
 different reaction profiles , particularly those involving noncarbonyl 
 electrophiles . the lack of comprehensive rate data for a range of 
 catalysts in different reactions is a barrier to understanding the 
 factors controlling catalytic activation . as a consequence , the relative 
 rates have been measured for an array of catalysts in two reactions 
 with different groups that interact with the catalysts . the sensor 
 signal has been analyzed with respect to reaction profile , catalyst 
 structure , acidity , and acceptor preference . our findings establish 
 the sensor as a useful substrate  surrogate  for probing 
 and gauging catalyst performance . moreover , the data unequivocally 
 establish that catalyst structure and binding mode are far more relevant 
 to catalytic activity than acidity . a key consideration in designing a method 
 for measuring hydrogen - bond strengths is the very broad range of these 
 noncovalent interactions ( 0.240 kcal / mol ) . observing the very weak range of these interactions is 
 a challenge with commonly employed spectroscopic techniques . for example , 
 despite successful application in measuring lewis acid binding effects , preliminary nmr studies proved too insensitive 
 for detecting the interactions of weak hydrogen - bonding catalysts 
 with a carbonyl acceptor . we proposed 
 an alternative approach using the sensitivity of uv  vis absorption 
 profiles , in which a change in electronic excitation of an acceptor 
 chromophore occurs upon binding to a hydrogen - bond donor ( scheme 1 ) . specifically , imidazopyrazinone s displays solvatochromism with protic solvents as well as color changes 
 with a small number of lewis acids . we 
 postulated that upon treatment with various hydrogen - bond donors , 
 the carbonyl moiety of s would act as an acceptor moiety . the resulting hydrogen - bonding interaction would alter the electronic 
 transition of the chromophore , detectable by simple uv  vis 
 spectroscopy . in line with this reasoning , treatment of sensor s in dichloromethane with various hydrogen - bond donors resulted 
 in 
 visible hypsochromic ( blue ) shifts ( figure 1 ) . importantly , compounds anticipated to be weaker donors , such as 
 diphenylthiourea ( 1 ) , yielded significant changes in 
 sensor signal . variation of binder concentration resulted in titration - like 
 behavior , with a measurable end point upon saturation of sensor with 
 catalyst . an array of catalysts ( chart 1 ) , 
 varying in structure and anticipated strength , was examined with the 
 colorimetric sensor , and the max upon saturation 
 was determined . response in the uv  vis spectrum of s upon increasing 
 amounts of 12 . [ s ] = 2.22  10 m in ch2cl2 ,   = 0 to 1.78  10 m. dft molecular orbital calculations were performed 
 on bound and 
 unbound sensor for selected hydrogen - bonding agents to gauge the orbital 
 perturbation ( table 1 ) . the calculated lowest 
 energy transition accurately predicts the observed absorbance maximum 
 for the free sensor . lumo energy 
 gap was larger for all bound complexes , in accord with the empirically 
 observed hypsochromic shift in figure 1 . an 
 increased shift ( lower max ) is predicted for binders 
 of ostensibly greater strength ( e.g. , proton > benzoic acid > 
 phenol ) . the 
 uv absorption behavior of the sensor with the hydrogen - bonding 
 agent can be represented as shown in figure 2a . the lowest energy electronic transition may be ascribed to the 
 n ( homo ) to  * ( lumo ) transition , e1 , corresponding to the measured max . as 
 supported by the above calculations , addition of a hydrogen - bonding 
 agent stabilizes the ground state ( homo ) to a greater extent than 
 the excited state ( lumo ) , i.e. , e3 > e2 . as a consequence , a 
 hypsochromic 
 shift is observed upon interaction of the sensor with the hydrogen - bond 
 donors . for comparison , figure 2b illustrates 
 the energy diagram for a typical reaction with a hydrogen - bonding 
 catalyst , in which catalysis is effected by lumo - lowering of the electrophile 
 ( ea ) . e2 is proportional to ea , i.e. , 
 the wavelength shift of the bound sensorcatalyst is proportional 
 to the rate enhancement afforded in a reaction with the hydrogen - bonding 
 catalyst . ( a ) proposed energy diagram of the lowest energy electronic transition 
 of the sensor upon interaction with catalysts of increasing strength , 
 corresponding to the hypsochromic wavelength shift ( max ) . ( b ) lumo - lowering of reactants via hydrogen - bonding catalysts , 
 corresponding to increased reaction rates ( krel ) . as shown in figure 1 , a continuous 
 wavelength shift was revealed upon saturation of the sensor with the 
 catalyst . the lack of two distinct peaks in intermediate measurements 
 containing both bound and unbound sensor indicates a rapid equilibration . thus , plots of absorbance vs [ catalyst ] ( see figure 3 for an example with bisamidinium 12 ) were used 
 to determine the binding constants ( keq ) for the sensorcatalyst 
 complex . a significant range of blue shifts was observed for the different 
 catalyst donors , ranging from 490 to 465 nm ( max 1030 nm ) . in general , catalysts with larger 
  max values possessed much stronger binding 
 constants . since e1 is proportional 
 to 1/max , the energetics of the interaction of the 
 sensor with the catalysts ( e3  
 e2 ) is proportional to 1/max(sensorcatalyst )  1/max(sensor ) . indeed , a good correlation of this inverse wavelength shift 
 with ln(keq ) was found ( figure 4 ) . note that in this plot , both axes are linearly proportional to 
 energy terms :  to the e of the sensor electronic absorption , and ln(keq ) to g of sensorcatalyst 
 formation . importantly , this relationship establishes the observed 
 wavelength shift as a reliable gauge for binding affinity of a catalyst 
 to the sensor molecule . uv - titration curve of catalyst 12 in ch2cl2 using [ s ] = 2.22  
 10 m. inlay : visible color change of sensor before 
 ( red ) and after 
 addition of 12 ( yellow ;   = 1.78  
 10 m ) . all titrations were performed with [ s ] = 2.22  10 m in ch2cl2 . using the sensorcatalyst wavelength shift as predictors 
 of catalyst reactivity yields several noteworthy observations . diol - based 30 ( taddol ) and silanol catalysts 31 and 32 afforded very weak shifts , despite application in numerous 
 transformations , including rawal s seminal report on the asymmetric 
 hetero diels  alder reaction . the 
 greater max shift of 32 compared to 
 the related monosilanol 31 mirrors the increased reactivity 
 of this silanediol scaffold , as elegantly reported by mattson and franz . benzoic acids 
 and phenols spanned the intermediate range of sensor shifts , with 
 trends clearly based on the electronic effects of aromatic substitution . although these structures are not as commonly incorporated as hydrogen - bond 
 catalysts , schafmeister and co - workers have recently demonstrated 
 the spiroligozyme catalyst 24 , containing a carefully 
 arranged carboxylic acid and phenol , as an effective ketosteroid isomerase 
 mimic for the aromatic claisen rearrangement.n , n-diaryl thioureas and 
 ureas , particularly those with multiple trifluoromethyl substituents 
 such as schreiner s catalyst 4 , afforded some of the largest sensor shifts , indicative 
 of the immense utility of these structures in various organocatalysts . the internally activated bf2-urea 9 provided the largest shift within this class , in line with 
 experimental reactivity data reported by mattson and co - workers . finally , formally cationic species , including 
 guanidinium , amidinium , and takenaka s azaindolium 14(22 ) were the strongest binders , with wavelength 
 shifts ranging from 26 to 34 nm ( max = 473465 
 nm ) . interestingly , one of the strongest noncationic binders was thiophosphoramide 16 , possessing a pocket of three potential n  h donors . squaramide - containing scaffolds have yielded excellent results as 
 hydrogen - bond activators ; however , these compounds 
 possess limited solubility , and are typically employed as heterogeneous 
 catalysts . representative squaramide 11 , containing the 
 common n-3,5-(cf3)2aryl and n-alkyl array , was synthesized , and gave an apparent 
 sensor end point of 480 nm . due to its relative insolubility , 
 an accurate binding equilibrium value could not be determined . it is worth noting the experimental ease with which the sensor 
 metric can be obtained . compound s itself is easily obtained 
 in 2 steps from commercial materials , and very little 
 sensor or catalyst ( particularly for strong catalysts ) is necessary 
 to obtain the wavelength shift . the titration experiment is largely 
 insensitive to moisture , as illustrated by the poor binding observed 
 in the sensor titration with water . applying the method of continuous 
 variation to the sensor with 
 catalyst 12 revealed a 1:1 binding stoichiometry with 
 the sensor molecule ( figure 5 ) . this observation is significant , since several 
 other binding situations may be postulated , including donation of 
 one catalyst molecule to several sensors ( 4 equivalent n job plot analysis of 
 catalyst 12 with sensor s showing 1:1 binding 
 stoichiometry . benzoic acids and phenols 
 offer useful templates to study electronic 
 effects on sensor signal due to availability and well - understood behavior 
 of aromatic substitution . due to solubility limitations , ortho - substituted benzoic acids were studied rather than the para - substituted analogs . the electronic effects from substitution on 
 the sensor interaction can be illustrated via a hammett - type plot , 
 as shown in figure 6 . as may be anticipated 
 from the brnsted catalysis law ( see section 2.6 for further discussion ) , increasingly electron - withdrawing 
 substituents on these structures correlate with larger hypsochromic 
 shifts of the sensorcatalyst complex . for both catalyst sets , highly linear relationships are evident with substituent  parameters 
 indicating that the wavelength shift provides an accurate readout 
 of electronic perturbation on the hydrogen - bonding ability . correlation 
 of hammett  parameters for o - benzoic acids 
 ( ortho ) and p - phenols ( para ) 
 with sensorcatalyst wavelength shifts . notably , the wavelength shifts seen with the sensor do not 
 correspond 
 directly with pka either in water ( figure 7a , r = 0.0007 ) or dmso 
 ( figure 7b , r = 
 0.0950 ) . however , correlations are observed for closely related catalyst 
 structures , wherein electronic perturbations modify the acidity of 
 the donor moiety without introducing significant secondary effects . this observation provides potential for the sensor to estimate pka values within a series of related compounds . persubstituted phenol 29 deviates from other phenolic 
 catalysts , which may be attributed to the increased steric demand 
 around the donating o plot of catalyst acidity in water ( a ) 
 or dmso ( b ) vs sensorcatalyst 
 wavelength shifts . the correlation of the 
 observed blue shift with the binding strength 
 across a large range of hydrogen - bond donors proved the metric to 
 be able to quantitatively detect these interactions . however , this 
 finding does not necessitate a correlation with catalyst 
 reactivity . in order for this correlation to occur , the sensor must 
 be a good facsimile of the substrate that is undergoing reaction . other factors , including alternate binding modes and steric effects , 
 might come into play when a substrate interacts with hydrogen - bonding 
 agent in a catalyzed reaction . to be a useful metric 
 for the community , the sensor signal must correlate to empirically 
 obtained rate enhancement via hydrogen - bond catalysis ( scheme 2 ) . myriad reaction profiles have been reported that 
 are established to proceed via hydrogen - bond activation of the electrophile 
 ( lumo - lowering activation ) . in order to best isolate the reactivity 
 enhancement offered by the catalysts strictly due to hydrogen - bonding , 
 we first targeted a reaction where the electrophile has only one possible 
 point of interaction with the catalyst , and the nucleophile does not 
 contain binding points ( i.e. , no heteroatoms ) . additionally , the reaction 
 should have minimal background rate and a method to easily analyze 
 starting material and/or product concentrations . the reaction of methyl vinyl ketone ( mvk ) with cyclopentadiene 
 ( cp ) offers a useful reaction platform that fulfills these criteria 
 ( scheme 3 ) , and has been used to gauge the 
 relative strength of thiourea and bisphenol catalysts previously . importantly , 
 the binding in the sensorcatalyst complex is very similar 
 to that of the mvkcatalyst intermediate as both interactions 
 arise from a carbonyl acting as a hydrogen - bond acceptor . systematic investigation of the diels  alder reaction 
 of 
 mvk and cp with a variety of catalysts was performed under pseudo - first 
 order conditions as described in scheme 3 . kinetic data was acquired via continuous sampling ( 5 min intervals ) 
 by h nmr spectroscopy , and each rate measurement was performed 
 in triplicate . relative rate constants , krel , were calculated as described in eq 1 from 
 the observed pseudo - first order rate constant kobs and background rate kbackground , and were normalized for catalyst concentration n. the resulting 
 values directly provide the rate enhancement afforded by the catalyst.1 as displayed in figure 8 , a plot of ln(krel ) against the 
 inverse sensor wavelength shift 
 of 18 catalysts shows an excellent correlation . catalysts with greater 
 blue shifts when treated with the sensor show greater activity in 
 the diels  alder reaction via correspondingly greater lumo lowering 
 of the ketone in the dienophile . more precisely , the change in energy 
 of the sensor upon binding with the catalyst is proportional to the 
 change in activation energy of the hydrogen - bond catalyzed diels  alder 
 reaction . correlation between the sensorcatalyst wavelength shift 
 and catalyst rate enhancement in the diels  alder reaction between 
 mvk and cp . the observed correlation 
 establishes that , at least in this class 
 of reaction , the sensor signal is a good indicator of lumo - lowering 
 ability of these small molecules as hydrogen - bond catalysts . importantly , 
 the results also indicate that the binding interaction of the sensor 
 with catalysts is similar to that of methyl vinyl ketone with catalyst , 
 i.e. the sensor is a useful gauge of carbonyl activation . the addition of 
 various nucleophiles into nitroalkenes is one of the most widely used 
 reaction motifs in hydrogen - bonding catalysts ; it is often used as 
 a measure of reactivity when developing and comparing novel catalyst 
 structures . to test the effectiveness of our sensor 
 metric beyond the diels  alder reaction crafts 
 addition of n - methylindole ( 34 ) into 
 nitrostyrene 35 ( scheme 4 ) . deuterated 35 was easily prepared via henry condensation using d3-nitromethane with the corresponding aldehyde . nucleophile 34 provides a reasonably active coupling 
 partner while minimizing potential catalyst interactions [ pka(h2o ) n - methylindolium 
 = 1.8 ] . thus , the effects of 
 hydrogen bonding catalysts on the activation of the styrene electrophile 
 via binding to the nitro acceptor can be cleanly delineated . significantly , the catalyzed rates of this reaction allow 
 comparison 
 of the effects of hydrogen - bonding catalysts on carbonyl acceptors 
 ( the sensor and mvk ) versus nitro acceptors ( nitrostyrene 35 ) as outlined in scheme 5 . while binding geometries 
 to carbonyl groups are anticipated to be similar , an analogous correlation 
 may not be automatically presumed for a nitro group . in particular , 
 the nitro group contains a formally delocalized negative charge across 
 three atoms , and has been suggested to form -activated 
 intermediates with certain catalyst structural types such as squaramides 
 and thioureas . as illustrated in figure 9 , kinetic reaction 
 data was acquired using h nmr spectroscopy . although initial h nmr spectroscopic studies with proteo-35 provided 
 usable data , employment of a deuterium label provides exceptional 
 signal isolation . moreover , overlap of signals from the catalyst is 
 completely mitigated , since only substrate , product , and internal 
 standard exhibit appreciable resonances . as a result , any 
 catalyst can be readily analyzed . ( a ) stacked h nmr plot and ( b ) kinetic profile for 
 the friedel  crafts reaction shown in scheme 4 using catalyst 12 . conditions :   = 1.33 m ,   = 0.133 m ,   = 0.133 
 m ,   = 2.67  10 m. the cdcl3 peak arises from natural abundance in chcl3 . crafts reaction 
 was studied under pseudo - first 
 order conditions using the broad series of hydrogen - bond catalysts 
 shown in chart 1 . the relative catalytic strength 
 of each catalyst was calculated according to eq 1 , using averaged kobs values 
 from duplicate trials . a plot of ln(krel ) and inverse sensor wavelength shift is shown in figure 10a . similar to the diels alder reaction , 
 and predicted based on sensor shifts , cationic binders proved to be 
 the most effective catalysts , followed by electron - deficient ureas 
 and thioureas . squaramide 11 , employed here as a heterogeneous 
 catalyst , provided moderate rate enhancement as predicted by its sensor 
 wavelength shift . the krel values 
 reported for these catalysts and 4 align closely with 
 the values measured in this work . ( a ) correlation observed between the 
 sensorcatalyst wavelength 
 shift and catalyst rate enhancement in the friedel  crafts reaction . the overall correlation of the sensor wavelength 
 shift with catalyst 
 strength for the friedel crafts reaction is good ( r2 = 0.84 ) , but not as strong as that found in the diels  alder 
 reaction ( r2 = 0.95 ) . analysis of this 
 data suggests that the binding interaction of a hydrogen - bonding catalyst 
 with the sensor carbonyl does not fully mimic that of a hydrogen - bonding 
 catalyst with the activated nitroalkene . closer inspection reveals 
 that the wavelength shift is correlated even more strongly to catalyst 
 strength within an isostructural catalyst series ( figure 10b ) . specifically , the catalysts can be placed in 
 four groups based on their general structure : benzoic acids , phenols , 
  y - type  binders , and other n  h binders . the 
 y - type group consists of catalysts possessing two n  h donor 
 groups separated by a single atom , such as ureas , thioureas , guanidines , 
 bis - sulfonamides , etc . the other n  h binders include those 
 catalysts that have more than one atom separating the donor array 
 ( squaramide 11 , bisamidinium 12 ) or can 
 only donate one n interestingly , the silanediol catalyst 32 exhibits reactivity falling nicely in line with benzoic acids , possibly 
 due to a similar o  h geometry . this analysis quantitatively 
 shows that y - type structures are superior for nitroalkene activation . in contrast , phenols provided the least activation relative to their 
 binding interaction with the sensor . overall , the sensor provides 
 a good assessment of relative reactivity 
 of hydrogen - bond catalysts in the friedel  crafts reaction . the presence of stronger correlations within catalyst structural classes 
 is consistent with some catalysts activating nitroalkenes via a different 
 mode ( e.g. , -binding ) that is not completely captured 
 by the interactions of the catalysts with the carbonyl of the sensor 
 molecule . this analysis underlines the complex nature of hydrogen - bonding , 
 emphasizing that caution must be exercised in generalizing catalyst 
 reactivity or selectivity from one reaction to another . a general equation to describe catalyst strength 
 for reaction r based on sensor response (  ) is presented in eq 2 . parameter rr ( slope ) represents the responsiveness of the rate per unit catalyst strength as determined by the sensor 
 measurement . parameter cr ( y - intercept ) corresponds to inherent complementarity of the catalyst to the electrophilic reaction partner.2 the parameter 
 values ( table 2 ) for the reactions shown in 
 scheme 3 ( diels  alder ) and scheme 4 ( friedel  crafts ) 
 were obtained using the kinetic data from figures 8 and 10 , respectively . comparison of 
 the rda and rfc values reveals that the friedel  crafts is more sensitive 
 to catalyst strength . in other words , the same catalyst produces a 
 greater relative rate enhancement for the friedel  crafts reaction 
 than for the diels  alder reaction . similarly , a given wavelength 
 shift of the sensor by a catalyst will cause a greater reactivity 
 change in the friedel  crafts vs the diels  alder reaction . 
 on the other hand , the cda and cfc values indicate the inherent complementarity of the electrophilic substrate with catalysts ; greater complementarity translates to greater reactivity . notably , the c values represent reactivity when there is no wavelength shift ( no 
 perturbation of the sensor by the catalysts ) and represent the lower 
 limit of lumo activation afforded by the catalyst . catalyst group - specific coefficients rr and cr can be 
 introduced ( eq 3 ) to account for variation if 
 the sensor binds the 
 catalyst differently than the reaction electrophile . due to the strong 
 correlation of the sensor shift to relative rates independent of catalyst 
 structure , coefficients are unnecessary for the diels  alder 
 reaction ( rda  cda  1 ) . as discussed in section 2.4 , the sensor does not completely model catalyst binding to 
 the nitrostyrene acceptor of the friedel  crafts reaction . accordingly , 
 the slope and intercept data from figure 10b were combined with the r and c values from table 2 to afford coefficient 
 values for rfc and cfc , respectively , as provided in table 3.3 the coefficient values in table 3 reveal 
 general trends between the different catalyst structural types and 
 rate in the friedel again , rfc values are a measure of responsiveness of a given catalyst architecture to a perturbation in sensor binding . 
 for y - type and phenolic catalysts , rfc is noticeably higher than the other n  h binders , and particularly 
 benzoic acids . thus , for the same amount of wavelength shift , the 
 phenol and y - type catalysts provide greater increases in reactivity 
 relative to the other n  h binders and benzoic acids . this observation 
 indicates that the sensor can assess electronic effects in a catalyst 
 series . comparison of the hammett effects on  ( figure 6 ; acid = 5.8 , 
 phenol = 4.4 ) with those on ln(krel ) ( acid = 0.60 , phenol = 0.33 ) provides support for this assertion ; 
 both measures show a stronger electronic effect for the carboxylic 
 acid series . on the other hand , lower cfc values 
 indicate the inherent complementarity of a given 
 catalyst architecture . for example , the y - type binders activate nitro 
 electrophiles to a greater extent at a given wavelength shift relative 
 to phenols or the other n  h binders . interestingly , the cfc value for benzoic acids would predict high 
 catalytic activity relative to y - type binders , but only in the weak 
 binding regime ( left side of plot ) . due to the low rfc value for benzoic acids , the trends invert such that 
 y - type binders are superior in the strong binding regime ( right side 
 of plot ) . considering both terms together , the y - type binders are 
 both more complementary to the nitroalkene and more efficient at lumo 
 lowering , thereby providing superior reactivity . acidity values have widely been used 
 as a guiding principle in hydrogen - bond catalyst design , under the 
 premise that a more acidic donor will form a stronger interaction 
 and stabilize the buildup of anionic charge in the transition state 
 to a greater extent . indeed , several reports have observed increased 
 activity with judicious electronic tuning of the donor hydrogen . however , even ostensibly subtle changes to catalyst structure can 
 cause secondary factors to override the reliability of pka as a predictive measure , as demonstrated by cheng s 
 recent study on thiourea derivatives 
 and even noted in the seminal work by hine on mono- and bis - phenols . having proved the effectiveness of the sensor 
 signal as a gauge for catalyst strength , we undertook a comparison 
 with acidity to determine the similarities and differences between 
 the two metrics . aggregate data for all catalysts spanning 3 
 orders of magnitude in reactivity for the diels  alder reaction 
 and 4 orders in the friedel  crafts reaction is organized by 
 increasing sensor wavelength shift in table 4 . recent efforts by schreiner and others provided accurate acidity values of common hydrogen - bond 
 donors . the brnsted catalysis equation ( eq 4 ) , which describes the relationship for the rate of an acid - catalyzed 
 reaction with the pka of the acid , was applied to this data.4 value for 2-naphthol . figures 11 and 12 display the results for selected 
 catalyst series in the diels  alder 
 and friedel  crafts reactions , respectively . these plots prove the linear free energy relationships 
 ( lfers ) between catalyst acceleration 
 and acidity among catalysts of very similar structure . in general , these lfers exhibited a narrow range of  values 
 ( 0.390.47 ; table 5 ) , indicating a similar degree of hydrogen - bonding in the 
 transition states and that these reactions are not proceeding through 
 formal protonation (  = 1 ) . slightly higher values found for 
 benzoic acids in the diels  alder (  = 0.57 ) indicate 
 a greater degree of proton transfer in the transition states consistent 
 with the ionic nature of benzoic acids . lower values for ureas in 
 the friedel  crafts (  = 0.31 ) indicate a lesser degree 
 of proton transfer in the transition states in line with the covalent 
 nature of the n  h bonds . brnsted catalysis plot for the 
 diels  alder reaction , 
 demonstrating lfers for closely related catalyst groups . more significantly , these figures clearly demonstrate 
 the inherent 
 limitations of estimating catalyst strength using acidity metrics . based solely on pka measurements , thioureas 
 would be predicted to provide much higher activity . in practice , the 
 opposite is observed where ureas exhibited greater ( 6 , 7 vs 2 , 3 ) or similar ( 8 vs 4 ) activation of the nitro group compared 
 to their thiourea analogues , despite the much greater acidity of the 
 thioureas ( 45 orders of magnitude difference ) . highly reactive 
 catalysts not belonging to a clearly defined series , including common 
 brnsted acids , are included in figure 11 and further highlight the disparity between acidity and activity . interestingly , takenaka s azaindolium catalyst 14 displayed much higher activity than ppts , despite similar acidities 
 and similar pyridinium in conclusion , a sensor is described that provides 
 an assessment 
 of the reactivity over 34 orders of magnitude for 33 hydrogen - bonding 
 catalysts . useful correlations are obtained between the wavelength 
 shifts that catalysts cause to the pyrazinone sensor and the rate - determining 
 steps in diels  alder and friedel  crafts reactions . as 
 a result , only the wavelength shifts upon saturation of the sensor 
 with catalysts need to be measured vs the more time - consuming titration 
 studies . consequently , the sensor may also find use as a rapid means 
 for measuring pka values in series of 
 related compounds . in contrast to established acidity ( pka ) values , the sensor wavelength shift is a 
 highly predictive metric 
 for the relative reactivity of catalysts encompassing a broad range 
 of structures and strengths . notable acidity - activity disparities 
 include cationic catalysts ( low acidity , high reactivity ) , and benzoic 
 acids ( high acidity , low reactivity ) , the strengths of which are more 
 accurately gauged by their interaction with the sensor . overall , the 
 sensor is a superior surrogate for the diverse electrophiles ( enone 
 and nitroalkene ) used compared to water and is better able to assess 
 secondary interactions . the data collected was used to formulate the 
 relationship described in eq 3 , which provides 
 a direct means of assessing the reactivity of a catalyst in a given 
 reaction using the sensor signal . the resulting parameters also reveal 
 relationships between substratecatalyst binding , catalyst - induced 
 lumo - lowering , and catalyst structure . investigation of additional 
 catalyzed reactions with the sensor , 
 empirically or computationally , has the potential to expand eq 3 to achieve quantitative predictive power across 
 a large range of reaction platforms and catalysts ( hydrogen bonding , 
 brnsted acid , and lewis acid ) .
a spectrophotometric sensor is described 
 that provides a useful 
 assessment of the lumo - lowering provided by catalysts in diels  alder 
 and friedel  crafts reactions . 
 a broad range of 33 hydrogen - bonding 
 catalysts was assessed with the sensor , and the relative rates in 
 the above reactions spanned 5 orders of magnitude as determined via 1h- and 2h nmr spectroscopic measurements , respectively . 
 the differences between the maximum wavelength shift of the sensor 
 with and without catalyst ( max1 ) 
 were found to correlate linearly with ln(krel ) values for both reactions , even though the substrate feature 
 that interacts with the catalyst differs significantly ( ketone vs 
 nitro ) . 
 the sensor provides an assessment of both the inherent 
 reactivity of a catalyst architecture as well as the sensitivity of the reaction to changes within an architecture . 
 in contrast , catalyst pka values are a 
 poor measure of reactivity , although correlations have been identified 
 within catalyst classes .